Olfactory nerve--a novel invasion route of Neisseria meningitidis to reach the meninges.

Science.gov (United States)

Sjölinder, Hong; Jonsson, Ann-Beth

2010-11-18

Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival.

Olfactory Nerve—A Novel Invasion Route of Neisseria meningitidis to Reach the Meninges

Science.gov (United States)

Sjölinder, Hong; Jonsson, Ann-Beth

2010-01-01

Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival. PMID:21124975

Refolding, purification and crystallization of the FrpB outer membrane iron transporter from Neisseria meningitidis

International Nuclear Information System (INIS)

Saleem, Muhammad; Prince, Stephen M.; Patel, Hema; Chan, Hannah; Feavers, Ian M.; Derrick, Jeremy P.

2012-01-01

The refolding, purification and crystallization of FrpB from the meningitis pathogen Neisseria meningitidis is described. FrpB is an integral outer membrane protein from the human pathogen Neisseria meningitidis. It is a member of the TonB-dependent transporter family and promotes the uptake of iron across the outer membrane. There is also evidence that FrpB is an antigen and hence a potential component of a vaccine against meningococcal meningitis. FrpB incorporating a polyhistidine tag was overexpressed in Escherichia coli into inclusion bodies. The protein was then solubilized in urea, refolded and purified to homogeneity. Two separate antigenic variants of FrpB were crystallized by sitting-drop vapour diffusion. Crystals of the F5-1 variant diffracted to 2.4 Å resolution and belonged to space group C2, with unit-cell parameters a = 176.5, b = 79.4, c = 75.9 Å, β = 98.3°. Crystal-packing calculations suggested the presence of a monomer in the asymmetric unit. Crystals of the F3-3 variant also diffracted to 2.4 Å resolution and belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 85.3, b = 104.6, c = 269.1 Å. Preliminary analysis suggested the presence of an FrpB trimer in the asymmetric unit

In silico analysis of different generation β lactams antibiotics with penicillin binding protein-2 of Neisseria meningitidis for curing meningococcal disease.

Science.gov (United States)

Tripathi, Vijay; Tripathi, Pooja; Srivastava, Navita; Gupta, Dwijendra

2014-12-01

Neisseria meningitidis is a gram negative, diplococcic pathogen responsible for the meningococcal disease and fulminant septicemia. Penicillin-binding proteins-2 (PBPs) is crucial for the cell wall biosynthesis during cell proliferation of N. meningitidis and these are the target for β-lactam antibiotics. For many years penicillin has been recognized as the antibiotic for meningococcal disease but the meningococcus has seemed to be antibiotic resistance. In the present work we have verified the molecular interaction of Penicillin binding protein-2 N. meningitidis to different generation of β-lactam antibiotics and concluded that the third generation of β-lactam antibiotics shows efficient binding with Penicillin binding protein-2 of N. meningitidis. On the basis of binding efficiency and inhibition constant, ceftazidime emerged as the most efficient antibiotic amongst the other advanced β-lactam antibiotics against Penicillin-binding protein-2 of N. meningitidis.

Impact of the conjugate vaccine, MenAfriVac, on carriage of serogroup A Neisseria meningitidis and disease transmission

OpenAIRE

Kristiansen, Paul Arne

2013-01-01

Neisseria meningitidis (Nm), also referred to as meningococcus, is a human commensal colonising the oropharynx, transmittable by close contact between healthy people. The bacterium can act as an opportunistic pathogen and cause bacterial meningitis and septicaemia. Meningococci are classified into 12 serogroups based on the composition of their polysaccharide (Ps) capsule. Six of these serogroups, serogroups A, B, C, W, X and Y cause meningococcal disease worldwide. The populations most affec...

Neisseria meningitidis ST11 Complex Isolates Associated with Nongonococcal Urethritis, Indiana, USA, 2015-2016.

Science.gov (United States)

Toh, Evelyn; Gangaiah, Dharanesh; Batteiger, Byron E; Williams, James A; Arno, Janet N; Tai, Albert; Batteiger, Teresa A; Nelson, David E

2017-02-01

At a clinic in Indianapolis, Indiana, USA, we observed an increase in Neisseria gonorrhoeae-negative men with suspected gonococcal urethritis who had urethral cultures positive for N. meningitidis. We describe genomes of 2 of these N. meningitidis sequence type 11 complex urethritis isolates. Clinical evidence suggests these isolates may represent an emerging urethrotropic clade.

Towards an improved Neisseria meningitidis B vaccine: vesicular PorA formulations

NARCIS (Netherlands)

Arigita Maza, C. (Carmen)

2003-01-01

There is a great need for vaccines against Neisseria meningitidis serogroup B. This is especially important in Western European countries, were approximately two thirds of the cases of meningococcal disease can be attributed to serogroup B strains. Against this serogroup, traditional vaccines based

Improved production process for native outer membrane vesicle vaccine against Neisseria meningitidis.

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Bas van de Waterbeemd

Full Text Available An improved detergent-free process has been developed to produce vaccine based on native outer membrane vesicles (NOMV against Neisseria meningitidis serogroup B. Performance was evaluated with the NonaMen vaccine concept, which provides broad coverage based on nine distinct PorA antigens. Scalable aseptic equipment was implemented, replacing undesirable steps like ultracentrifugation, inactivation with phenol, and the use of preservatives. The resulting process is more consistent and gives a higher yield than published reference processes, enabling NOMV production at commercial scale. Product quality met preliminary specifications for 9 consecutive batches, and an ongoing study confirmed real-time stability up to 12 months after production. As the NOMV had low endotoxic activity and induced high bactericidal titres in mice, they are expected to be safe and effective in humans. The production process is not limited to NonaMen and may be applicable for other N. meningitidis serogroups and other gram-negative pathogens. The current results therefore facilitate the late-stage development and clinical evaluation of NOMV vaccines.

A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria.

Science.gov (United States)

Jen, Freda E-C; Djoko, Karrera Y; Bent, Stephen J; Day, Christopher J; McEwan, Alastair G; Jennings, Michael P

2015-09-01

Under conditions of low oxygen availability, Neisseria meningitidis and Neisseria gonorrhoeae are able to respire via a partial denitrification pathway in which nitrite is converted to nitrous oxide. In this process, nitrite reductase (AniA), a copper (Cu)-containing protein converts nitrite to NO, and this product is converted to nitrous oxide by nitric oxide reductase (NorB). NorB also confers protection against toxic NO, and so we devised a conditional lethal screen, using a norB mutant, to identify mutants that were resistant to nitrite-dependent killing. After random-deletion mutagenesis of N. meningitidis, this genetic screen identified a gene encoding a Cu chaperone that is essential for AniA function, AccA. Purified AccA binds one Cu (I) ion and also possesses a second binding site for Cu (II). This novel periplasmic Cu chaperone (AccA) appears to be essential for provision of Cu ions to AniA of pathogenic Neisseria to generate an active nitrite reductase. Apart from the Neisseria genus, AccA is distributed across a wide range of environmental Proteobacteria species. © FASEB.

Virulence evolution of the human pathogen Neisseria meningitidis by recombination in the core and accessory genome.

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Biju Joseph

Full Text Available BACKGROUND: Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH and multilocus sequence typing (MLST of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences. PRINCIPAL FINDINGS: We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins. CONCLUSIONS: Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence.

Multiple mechanisms of phase variation of PorA in Neisseria meningitidis

NARCIS (Netherlands)

van der Ende, A.; Hopman, C. T.; Dankert, J.

2000-01-01

Previously, we reported that PorA expression in Neisseria meningitidis is modulated by variation in the length of the homopolymeric tract of guanidine residues between the -35 and -10 regions of the promoter or by deletion of porA. To reveal additional mechanisms of variation in PorA expression, the

Neisseria meningitidis ST11 Complex Isolates Associated with Nongonococcal Urethritis, Indiana, USA, 2015–2016

Science.gov (United States)

Toh, Evelyn; Gangaiah, Dharanesh; Batteiger, Byron E.; Williams, James A.; Arno, Janet N.; Tai, Albert; Batteiger, Teresa A.

2017-01-01

At a clinic in Indianapolis, Indiana, USA, we observed an increase in Neisseria gonorrhoeae–negative men with suspected gonococcal urethritis who had urethral cultures positive for N. meningitidis. We describe genomes of 2 of these N. meningitidis sequence type 11 complex urethritis isolates. Clinical evidence suggests these isolates may represent an emerging urethrotropic clade. PMID:28098538

Phasevarions mediate random switching of gene expression in pathogenic Neisseria.

Directory of Open Access Journals (Sweden)

Yogitha N Srikhanta

2009-04-01

Full Text Available Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression. In Haemophilus influenzae, the random switching of the modA gene controls expression of a phase-variable regulon of genes (a "phasevarion", via differential methylation of the genome in the modA ON and OFF states. Phase-variable mod genes are also present in Neisseria meningitidis and Neisseria gonorrhoeae, suggesting that phasevarions may occur in these important human pathogens. Phylogenetic studies on phase-variable mod genes associated with type III restriction modification (R-M systems revealed that these organisms have two distinct mod genes--modA and modB. There are also distinct alleles of modA (abundant: modA11, 12, 13; minor: modA4, 15, 18 and modB (modB1, 2. These alleles differ only in their DNA recognition domain. ModA11 was only found in N. meningitidis and modA13 only in N. gonorrhoeae. The recognition site for the modA13 methyltransferase in N. gonorrhoeae strain FA1090 was identified as 5'-AGAAA-3'. Mutant strains lacking the modA11, 12 or 13 genes were made in N. meningitidis and N. gonorrhoeae and their phenotype analyzed in comparison to a corresponding mod ON wild-type strain. Microarray analysis revealed that in all three modA alleles multiple genes were either upregulated or downregulated, some of which were virulence-associated. For example, in N. meningitidis MC58 (modA11, differentially expressed genes included those encoding the candidate vaccine antigens lactoferrin binding proteins A and B. Functional studies using N. gonorrhoeae FA1090 and the clinical isolate O1G1370 confirmed that modA13 ON and OFF strains have distinct phenotypes in antimicrobial resistance, in a primary human cervical epithelial cell model of infection, and in biofilm formation. This study, in conjunction with our previous work in H. influenzae, indicates

Phasevarions mediate random switching of gene expression in pathogenic Neisseria.

Science.gov (United States)

Srikhanta, Yogitha N; Dowideit, Stefanie J; Edwards, Jennifer L; Falsetta, Megan L; Wu, Hsing-Ju; Harrison, Odile B; Fox, Kate L; Seib, Kate L; Maguire, Tina L; Wang, Andrew H-J; Maiden, Martin C; Grimmond, Sean M; Apicella, Michael A; Jennings, Michael P

2009-04-01

Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae, the random switching of the modA gene controls expression of a phase-variable regulon of genes (a "phasevarion"), via differential methylation of the genome in the modA ON and OFF states. Phase-variable mod genes are also present in Neisseria meningitidis and Neisseria gonorrhoeae, suggesting that phasevarions may occur in these important human pathogens. Phylogenetic studies on phase-variable mod genes associated with type III restriction modification (R-M) systems revealed that these organisms have two distinct mod genes--modA and modB. There are also distinct alleles of modA (abundant: modA11, 12, 13; minor: modA4, 15, 18) and modB (modB1, 2). These alleles differ only in their DNA recognition domain. ModA11 was only found in N. meningitidis and modA13 only in N. gonorrhoeae. The recognition site for the modA13 methyltransferase in N. gonorrhoeae strain FA1090 was identified as 5'-AGAAA-3'. Mutant strains lacking the modA11, 12 or 13 genes were made in N. meningitidis and N. gonorrhoeae and their phenotype analyzed in comparison to a corresponding mod ON wild-type strain. Microarray analysis revealed that in all three modA alleles multiple genes were either upregulated or downregulated, some of which were virulence-associated. For example, in N. meningitidis MC58 (modA11), differentially expressed genes included those encoding the candidate vaccine antigens lactoferrin binding proteins A and B. Functional studies using N. gonorrhoeae FA1090 and the clinical isolate O1G1370 confirmed that modA13 ON and OFF strains have distinct phenotypes in antimicrobial resistance, in a primary human cervical epithelial cell model of infection, and in biofilm formation. This study, in conjunction with our previous work in H. influenzae, indicates that

The iron-regulated transcriptome and proteome of Neisseria meningitidis serogroup C

Czech Academy of Sciences Publication Activity Database

Basler, Marek; Linhartová, Irena; Halada, Petr; Novotná, Jana; Bezoušková, Silvia; Osička, Radim; Weiser, Jaroslav; Vohradský, Jiří; Šebo, Peter

2006-01-01

Roč. 6, č. 23 (2006), s. 6194-6206 ISSN 1615-9853 R&D Projects: GA ČR GA310/04/0804; GA MZe 1G46068 Institutional research plan: CEZ:AV0Z50200510 Keywords : iron regulation * Neisseria meningitidis * proteome Subject RIV: EE - Microbiology, Virology Impact factor: 5.735, year: 2006

Study of 138 Neisseria meningitidis strains isolated from blood or cerebrospinal fluid in Lombardy between 2007 and 2010

Directory of Open Access Journals (Sweden)

Laura Daprai

2012-06-01

Full Text Available Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b cause the majority of cases of bacterial septicaemia in children and young adults. Disease epidemiology is evolving rapidly due to the introduction of vaccines and changing in bacterial antibiotic-resistance patterns. (Asymptomatic nasopharyngeal colonization with Neisseria meningitides occurs in 5-10% of adult. The aim of this study was to calculate the frequency of each serogroup of this pathogens involved in invasive infection and to study susceptibility to antibiotics of these strains. Between March 2007 and June 2010 we received, from 43 hospitals of Lombardy, 138 strains of Neisseria meningitidis, from 138 patients aged (2-80yrs. The most frequent serogroup was B (58%, followed by serogroup C (34%, serogroup G (4% and W 135 (2%. Serogroup A end X accounted for 1% of invasive infection, each. We observed a decrease in susceptibility towards penicillin in 38% of strains. In addition we studied, by REP- PCR, genotype of 9 strains selected on the basis of epidemiological data.Among these strains, 3 different clusters according to the 3 small epidemic outbreaks occurred between June and September 2009, were recognised. Seven of these strains, although belonged to the same serogroup, brought about two different clusters. The present findings demonstrated that phenotypic data are not sufficient to define epidemic clusters, therefore molecular genotyping is required.

Laboratory Predictors of Meningococcal Disease And Vaccination in Children: studies on the host immune response against Neisseria meningitidis

NARCIS (Netherlands)

C.L. Vermont (Clementien)

2004-01-01

markdownabstract__Abstract__ Neisseria meningitidis is a gram-negative diplococcus which was first identified by Anton Weichselbaum in 1887. Strains of N. meningitidis can be classified into serogroups based upon the different composition of its capsular polysaccharide. Thirteen serogroups

Deep sequencing whole transcriptome exploration of the σE regulon in Neisseria meningitidis.

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Robert Antonius Gerhardus Huis in 't Veld

Full Text Available Bacteria live in an ever-changing environment and must alter protein expression promptly to adapt to these changes and survive. Specific response genes that are regulated by a subset of alternative σ(70-like transcription factors have evolved in order to respond to this changing environment. Recently, we have described the existence of a σ(E regulon including the anti-σ-factor MseR in the obligate human bacterial pathogen Neisseria meningitidis. To unravel the complete σ(E regulon in N. meningitidis, we sequenced total RNA transcriptional content of wild type meningococci and compared it with that of mseR mutant cells (ΔmseR in which σ(E is highly expressed. Eleven coding genes and one non-coding gene were found to be differentially expressed between H44/76 wildtype and H44/76ΔmseR cells. Five of the 6 genes of the σ(E operon, msrA/msrB, and the gene encoding a pepSY-associated TM helix family protein showed enhanced transcription, whilst aniA encoding a nitrite reductase and nspA encoding the vaccine candidate Neisserial surface protein A showed decreased transcription. Analysis of differential expression in IGRs showed enhanced transcription of a non-coding RNA molecule, identifying a σ(E dependent small non-coding RNA. Together this constitutes the first complete exploration of an alternative σ-factor regulon in N. meningitidis. The results direct to a relatively small regulon indicative for a strictly defined response consistent with a relatively stable niche, the human throat, where N. meningitidis resides.

Epidemiological markers in Neisseria meningitidis: an estimate of the performance of genotyping vs phenotyping

DEFF Research Database (Denmark)

Weis, N; Lind, I

1998-01-01

In order to estimate the performance of genotypic vs phenotypic characterization of Neisseria meningitidis, 2 methods, DNA fingerprinting and multilocus enzyme electrophoresis (MEE), were assessed as regards applicability, reproducibility and discriminating capacity. 50 serogroup B and 52 serogroup...... C Neisseria meningitidis strains from 96 patients with meningococcal disease and 22 serogroup C strains from healthy carriers were investigated. Both methods were 100% applicable to meningococcal strains and results of DNA fingerprinting as well as of MEE were reproducible. The number of types...... defined by DNA fingerprinting and MEE as compared to that defined by phenotypic characteristics (serogroup, serotype, serosubtype and sulphonamide resistance) was as follows: for serogroup B strains from patients, 11 and 12 vs 8; for serogroup C strains from patients, 10 and 15 vs 8; and for serogroup C...

Comparison of commercial diagnostic tests for identification of serogroup antigens of Neisseria meningitidis

NARCIS (Netherlands)

van der Ende, A.; Schuurman, I. G.; Hopman, C. T.; Fijen, C. A.; Dankert, J.

1995-01-01

In the study that is described the sensitivities and specificities of three commercial tests and the standard Reference Laboratory test, used since 1961, to identify Neisseria meningitidis serogroups were compared. The tests marketed by Difco, Murex/Wellcome, and Sanofi/Pasteur showed overall

Meropenem susceptibility of Neisseria meningitidis and Streptococcus pneumoniae from meningitis patients in The Netherlands

NARCIS (Netherlands)

van de Beek, D.; Hensen, E. F.; Spanjaard, L.; de Gans, J.; Enting, R. H.; Dankert, J.

1997-01-01

In-vitro susceptibility of 299 Neisseria meningitidis and 157 Streptococcus pneumoniae strains from meningitis patients in The Netherlands in 1993 and 1994 to meropenem was determined using the Etest. Susceptibility to penicillin, ceftriaxone, and chloramphenicol was also determined. Rifampicin

A first meningococcal meningitis case caused by serogroup Ⅹ Neisseria meningitidis strains in China

Institute of Scientific and Technical Information of China (English)

CHEN Chao; UANG Ying-chun; ZHANG Tie-gang; HE Jing-guo; WU Jiang; CHEN Li-juan; LIU Jun-feng; PANG Xing-huo; YANG Jie; SHAO Zhu-jun

2008-01-01

@@ Neisseria meningitidis is the leading cause of bacterial meningitis and classified into 13 serogroups based on the immunological reactivity of the capsular polysaccharide.1 Serogroups A,B,C,W135 and Y are the most common causes of meningitis.2

Neisseria meningitidis rifampicin resistant strains: analysis of protein differentially expressed

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Schininà Maria

2010-09-01

Full Text Available Abstract Background Several mutations have been described as responsible for rifampicin resistance in Neisseria meningitidis. However, the intriguing question on why these strains are so rare remains open. The aim of this study was to investigate the protein content and to identify differential expression in specific proteins in two rifampicin resistant and one susceptible meningococci using two-dimensional electrophoresis (2-DE combined with mass spectrometry. Results In our experimental conditions, able to resolve soluble proteins with an isoelectric point between 4 and 7, twenty-three proteins have been found differentially expressed in the two resistant strains compared to the susceptible. Some of them, involved in the main metabolic pathways, showed an increased expression, mainly in the catabolism of pyruvate and in the tricarboxylic acid cycle. A decreased expression of proteins belonging to gene regulation and to those involved in the folding of polypeptides has also been observed. 2-DE analysis showed the presence of four proteins displaying a shift in their isoelectric point in both resistant strains, confirmed by the presence of amino acid changes in the sequence analysis, absent in the susceptible. Conclusions The analysis of differentially expressed proteins suggests that an intricate series of events occurs in N. meningitidis rifampicin resistant strains and the results here reported may be considered a starting point in understanding their decreased invasion capacity. In fact, they support the hypothesis that the presence of more than one protein differentially expressed, having a role in the metabolism of the meningococcus, influences its ability to infect and to spread in the population. Different reports have described and discussed how a drug resistant pathogen shows a high biological cost for survival and that may also explain why, for some pathogens, the rate of resistant organisms is relatively low considering the

Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 Protease

DEFF Research Database (Denmark)

Vidarsson, G; Overbeeke, N; Stemerding, AM

2005-01-01

Neisseria meningitidis secretes a protease that specifically cleaves the hinge region of immunoglobulin A1 (IgA1), releasing the effector (Fc) domain of IgA1 from the antigen binding (Fab) determinants. Theoretically, the remaining Fab fragments can block pathogen receptors or toxins and still...

Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 Protease

NARCIS (Netherlands)

Vidarsson, Gestur; Overbeeke, Natasja; Stemerding, Annette M.; van den Dobbelsteen, Germie; van Ulsen, Peter; van der Ley, Peter; Kilian, Mogens; van de Winkel, Jan G. J.

2005-01-01

Neisseria meningitidis secretes a protease that specifically cleaves the hinge region of immunoglobulin A1 (IgA1), releasing the effector (Fc) domain of IgA1 from the antigen binding (Fab) determinants. Theoretically, the remaining Fab fragments can block pathogen receptors or toxins and still

Survivors of septic shock caused by Neisseria meningitidis in childhood: psychosocial outcomes in young adulthood

NARCIS (Netherlands)

Vermunt, Lindy C.; Buysse, Corinne M.; Joosten, Koen F.; Duivenvoorden, Hugo J.; Hazelzet, Jan A.; Verhulst, Frank C.; Utens, Elisabeth M.

2011-01-01

To investigate long-term psychosocial outcomes in young adults who survived septic shock caused by Neisseria meningitidis (meningococcal septic shock) during childhood. A cross-sectional study. The psychological investigation took place in the department of Child and Adolescent Psychiatry of the

Survivors of septic shock caused by Neisseria meningitidis in childhood : Psychosocial outcomes in young adulthood

NARCIS (Netherlands)

Vermunt, Lindy C.; Buysse, Corinne M.; Joosten, Koen F.; Duivenvoorden, Hugo J.; Hazelzet, Jan A.; Verhulst, Frank C.; Utens, Elisabeth M.

Objective: To investigate long-term psychosocial outcomes in young adults who survived septic shock caused by Neisseria meningitidis (meningococcal septic shock) during childhood. Design: A cross-sectional study. Setting: The psychological investigation took place in the department of Child and

Zinc piracy as a mechanism of Neisseria meningitidis for evasion of nutritional immunity.

Directory of Open Access Journals (Sweden)

Michiel Stork

2013-10-01

Full Text Available The outer membrane of Gram-negative bacteria functions as a permeability barrier that protects these bacteria against harmful compounds in the environment. Most nutrients pass the outer membrane by passive diffusion via pore-forming proteins known as porins. However, diffusion can only satisfy the growth requirements if the extracellular concentration of the nutrients is high. In the vertebrate host, the sequestration of essential nutrient metals is an important defense mechanism that limits the growth of invading pathogens, a process known as "nutritional immunity." The acquisition of scarce nutrients from the environment is mediated by receptors in the outer membrane in an energy-requiring process. Most characterized receptors are involved in the acquisition of iron. In this study, we characterized a hitherto unknown receptor from Neisseria meningitidis, a causative agent of sepsis and meningitis. Expression of this receptor, designated CbpA, is induced when the bacteria are grown under zinc limitation. We demonstrate that CbpA functions as a receptor for calprotectin, a protein that is massively produced by neutrophils and other cells and that has been shown to limit bacterial growth by chelating Zn²⁺ and Mn²⁺ ions. Expression of CbpA enables N. meningitidis to survive and propagate in the presence of calprotectin and to use calprotectin as a zinc source. Besides CbpA, also the TonB protein, which couples energy of the proton gradient across the inner membrane to receptor-mediated transport across the outer membrane, is required for the process. CbpA was found to be expressed in all N. meningitidis strains examined, consistent with a vital role for the protein when the bacteria reside in the host. Together, our results demonstrate that N. meningitidis is able to subvert an important defense mechanism of the human host and to utilize calprotectin to promote its growth.

Multiple-locus variable-number tandem repeat analysis of Neisseria meningitidis yields groupings similar to those obtained by multilocus sequence typing.

NARCIS (Netherlands)

Schouls, Leo M; Ende, Arie van der; Damen, Marjolein; Pol, Ingrid van de

2006-01-01

We identified many variable-number tandem repeat (VNTR) loci in the genomes of Neisseria meningitidis serogroups A, B, and C and utilized a number of these loci to develop a multiple-locus variable-number tandem repeat analysis (MLVA). Eighty-five N. meningitidis serogroup B and C isolates obtained

Crystallographic characterization of the outer membrane lipoprotein FrpD from Neisseria meningitidis

Czech Academy of Sciences Publication Activity Database

Sviridova, Ekaterina; Bumba, Ladislav; Řezáčová, Pavlína; Veverka, Václav; Šebo, Peter; Kutá-Smatanová, Ivana

2015-01-01

Roč. 22, č. 1 (2015), s. 57-58 ISSN 1211-5894. [Discussions in Structural Molecular Biology. Annual Meeting of the Czech Society for Structural Biology /13./. 19.03.2015-21.03.2015, Nové Hrady] R&D Projects: GA ČR(CZ) GAP207/11/0717; GA MŠk(CZ) LC06010 Institutional support: RVO:61388963 ; RVO:67179843 ; RVO:61388971 Keywords : FrpD * Neisseria meningitidis Subject RIV: CE - Biochemistry

Backbone resonance assignments of the outer membrane lipoprotein FrpD from Neisseria meningitidis

Czech Academy of Sciences Publication Activity Database

Bumba, Ladislav; Sviridova, E.; Kutá-Smatanová, Ivana; Řezáčová, Pavlína; Veverka, Václav

2014-01-01

Roč. 8, č. 1 (2014), s. 53-55 ISSN 1874-2718 R&D Projects: GA ČR(CZ) GAP207/11/0717; GA MŠk(CZ) LK11205 Institutional support: RVO:61388963 ; RVO:61388971 ; RVO:67179843 Keywords : Neisseria meningitidis * FrpC * FrpD * backbone assignments * NMR * iron-regulated protein Subject RIV: CE - Biochemistry Impact factor: 0.760, year: 2014

Fit genotypes and escape variants of subgroup III Neisseria meningitidis during three pandemics of epidemic meningitis

NARCIS (Netherlands)

Zhu, P.; van der Ende, A.; Falush, D.; Brieske, N.; Morelli, G.; Linz, B.; Popovic, T.; Schuurman, I. G.; Adegbola, R. A.; Zurth, K.; Gagneux, S.; Platonov, A. E.; Riou, J. Y.; Caugant, D. A.; Nicolas, P.; Achtman, M.

2001-01-01

The genetic variability at six polymorphic loci was examined within a global collection of 502 isolates of subgroup III, serogroup A Neisseria meningitidis. Nine "genoclouds" were identified, consisting of genotypes that were isolated repeatedly plus 48 descendent genotypes that were isolated

Comparison of three methods for identification of pathogenic Neisseria species

Energy Technology Data Exchange (ETDEWEB)

Appelbaum, P.C.; Lawrence, R.B.

1979-05-01

A radiometric procedure was compared with the Minitek and Cystine Trypticase Agar sugar degradation methods for identification of 113 Neisseria species (58 Neisseria meningitidis, 51 Neisseria gonorrhoeae, 2 Neisseria lactamica, 2 Neisseria sicca). Identification of meningococci and gonoccoi was confirmed by agglutination and fluorescent antibody techniques, respectively. The Minitek method identified 97% of meningococci, 92% of gonococci, and 100% of other Neisseria after 4 h of incubation. The radiometric (Bactec) procedure identified 100% of gonococci and 100% of miscellaneous Neisseria after 3 h, but problems were encountered with meningococci: 45% of the later strains yielded index values for fructose between 20 and 28 (recommended negative cut-off point, less than 20), with strongly positive (greater than 100) glucose and maltose and negative o-nitrophenyl-beta-0-galactopyranoside reactions in all 58 strains. The Cystine Trypticase Agar method identified 91% of meningococci, ases.

Genomic Characterization of Urethritis-Associated Neisseria meningitidis Shows that a Wide Range of N. meningitidis Strains Can Cause Urethritis.

Science.gov (United States)

Ma, Kevin C; Unemo, Magnus; Jeverica, Samo; Kirkcaldy, Robert D; Takahashi, Hideyuki; Ohnishi, Makoto; Grad, Yonatan H

2017-12-01

Neisseria meningitidis , typically a resident of the oro- or nasopharynx and the causative agent of meningococcal meningitis and meningococcemia, is capable of invading and colonizing the urogenital tract. This can result in urethritis, akin to the syndrome caused by its sister species, N. gonorrhoeae , the etiologic agent of gonorrhea. Recently, meningococcal strains associated with outbreaks of urethritis were reported to share genetic characteristics with the gonococcus, raising the question of the extent to which these strains contain features that promote adaptation to the genitourinary niche, making them gonococcus-like and distinguishing them from other N. meningitidis strains. Here, we analyzed the genomes of 39 diverse N. meningitidis isolates associated with urethritis, collected independently over a decade and across three continents. In particular, we characterized the diversity of the nitrite reductase gene ( aniA ), the factor H-binding protein gene ( fHbp ), and the capsule biosynthetic locus, all of which are loci previously suggested to be associated with urogenital colonization. We observed notable diversity, including frameshift variants, in aniA and fHbp and the presence of intact, disrupted, and absent capsule biosynthetic genes, indicating that urogenital colonization and urethritis caused by N. meningitidis are possible across a range of meningococcal genotypes. Previously identified allelic patterns in urethritis-associated N. meningitidis strains may reflect genetic diversity in the underlying meningococcal population rather than novel adaptation to the urogenital tract. Copyright © 2017 American Society for Microbiology.

The Neisseria meningitidis Outer Membrane Lipoprotein FrpD Binds the RTX Protein FrpC

Czech Academy of Sciences Publication Activity Database

Procházková, Kateřina; Osička, Radim; Linhartová, Irena; Halada, Petr; Šulc, Miroslav; Šebo, Peter

2005-01-01

Roč. 280, č. 5 (2005), s. 3251-3258 ISSN 0021-9258 R&D Projects: GA ČR GA310/02/1448 Grant - others:Howard Hughes Medical Institute International Research Scholarship Award 55000334 Institutional research plan: CEZ:AV0Z50200510 Keywords : neisseria meningitidis * FrpD * FrpC Subject RIV: EE - Microbiology, Virology Impact factor: 5.854, year: 2005

NmeSI restriction-modification system identified by representational difference analysis of a hypervirulent Neisseria meningitidis strain

NARCIS (Netherlands)

Bart, A.; Pannekoek, Y.; Dankert, J.; van der Ende, A.

2001-01-01

Neisseria meningitidis is a gram-negative bacterium that may cause meningitis, sepsis, or both. The increase in the incidence of meningococcal disease in various countries in the past 2 decades is mainly due the genotypically related lineage III meningococci. The chromosomal DNA differences between

Self-esteem in children and adolescents after septic shock caused by Neisseria meningitidis: scars do matter

NARCIS (Netherlands)

Vermunt, Lindy C.; Buysse, Corinne M.; Joosten, Koen F.; Oranje, Arnold P.; Hazelzet, Jan A.; Verhulst, Frank C.; Utens, Elisabeth M.

2008-01-01

To investigate self-esteem and its relation to scars, amputations, and orthopedic sequelae in children and adolescents long term after meningococcal septic shock (MSS) caused by Neisseria meningitidis. The Dutch versions of the Self-Perception Profile for Children (SPP-C; 8-11 years) and the

Preliminary crystallographic data of the three homologues of the thiol–disulfide oxidoreductase DsbA in Neisseria meningitidis

Energy Technology Data Exchange (ETDEWEB)

Lafaye, Céline [Laboratoire des Protéines Membranaires, Institut de Biologie Structurale, CEA/CNRS/Université Joseph Fourier, 41 Rue Jules Horowitz, 38027 Grenoble CEDEX 01 (France); Iwena, Thomas; Ferrer, Jean-Luc [Laboratoire de Cristallogénèse et Cristallisation des Protéines, Institut de Biologie Structurale, CEA/CNRS/Université Joseph Fourier, 41 Rue Jules Horowitz, 38027 Grenoble CEDEX 01 (France); Kroll, J. Simon [Department of Paediatrics, Imperial College London, St Mary’s Hospital Campus, Norfolk Place, London W2 1PG (United Kingdom); Griat, Mickael; Serre, Laurence, E-mail: laurence.serre@ibs.fr [Laboratoire des Protéines Membranaires, Institut de Biologie Structurale, CEA/CNRS/Université Joseph Fourier, 41 Rue Jules Horowitz, 38027 Grenoble CEDEX 01 (France)

2008-02-01

The Neisseria meningitidis genome possesses three genes encoding active DsbAs. To throw light on the reason for this genetic multiplicity, the three enzymes have been purified and crystallized. Bacterial virulence depends on the correct folding of surface-exposed proteins, a process that is catalyzed by the thiol-disulfide oxidoreductase DsbA, which facilitates the synthesis of disulfide bonds in Gram-negative bacteria. Uniquely among bacteria, the Neisseria meningitidis genome possesses three genes encoding active DsbAs: DsbA1, DsbA2 and DsbA3. DsbA1 and DsbA2 have been characterized as lipoproteins involved in natural competence and in host-interactive biology, while the function of DsbA3 remains unknown. In an attempt to shed light on the reason for this multiplicity of dsbA genes, the three enzymes from N. meningitidis have been purified and crystallized in the presence of high concentrations of ammonium sulfate. The best crystals were obtained using DsbA1 and DsbA3; they belong to the orthorhombic and tetragonal systems and diffract to 1.5 and 2.7 Å resolution, respectively.

Enhancement of recovery of Neisseria meningitidis by gelatin in blood culture media.

OpenAIRE

Pai, C H; Sorger, S

1981-01-01

The efficacy of gelatin for the recovery of Neisseria meningitidis from blood cultures was evaluated in a clinical setting. The organism was isolated from seven patients with meningococcal infections in blood culture media containing 1% gelatin. In contrast, only two blood cultures from these patients were positive in media without gelatin (P less than 0.05). Gelatin did not influence the recovery of other organisms isolated during this study. Conventional blood culture media may be supplemen...

NMR assignment of intrinsically disordered self-processing module of the FrpC protein of Neisseria meningitidis

Czech Academy of Sciences Publication Activity Database

Kubáň, V.; Nováček, J.; Bumba, Ladislav; Žídek, L.

2015-01-01

Roč. 9, č. 2 (2015), s. 435-440 ISSN 1874-2718 R&D Projects: GA ČR(CZ) GAP207/11/0717 Institutional support: RVO:61388971 Keywords : FrpC * Self-processing module * Neisseria meningitidis Subject RIV: EE - Microbiology, Virology Impact factor: 0.687, year: 2015

Deletion of porA by recombination between clusters of repetitive extragenic palindromic sequences in Neisseria meningitidis

NARCIS (Netherlands)

van der Ende, A.; Hopman, C. T.; Dankert, J.

1999-01-01

PorA is an important component in a vaccine against infection with Neisseria meningitidis. However, porA-negative meningococci were isolated from patients, thereby potentially limiting the role of PorA-mediated immunity. To analyze the mechanism by which the porA deletion occurred, the regions

Vigilancia de Neisseria meningitidis en Argentina, 1993-2005: distribución de serogrupos, serotipos y serosubtipos causantes de enfermedad invasiva Surveillance of Neisseria meningitidis in Argentina, 1993-2005: Distribution of serogroups, serotypes and serosubtypes isolated from invasive disease

OpenAIRE

L. Chiavetta; E. Chávez; A. Ruzic; M. Mollerach; M. Regueira

2007-01-01

Neisseria meningitidis es agente causal de enfermedades severas como meningitis, bacteriemia y síndrome de shock séptico. Se presenta la distribución en serogrupos, serotipos y serosubtipos de 2244 aislamientos de N. meningitidis obtenidos de cuadros de meningitis y/o meningococcemia durante el período 1993-2005 y analizados en el Laboratorio Nacional de Referencia del INEI-ANLIS "Dr. Carlos G. Malbrán". Estos aislamientos eran provenientes de 33 hospitales de todo el país, conformados en una...

Detection of Neisseria meningitidis in a paediatric patient with septic arthritis using multiplexed diagnostic PCR targeting meningitis/encephalitis (ME).

LENUS (Irish Health Repository)

O'Sullivan, Donnchadh

2018-03-23

Neisseria meningitidis is associated with meningitis and septicemia. Septic meningococcal arthritis is relatively uncommon and its diagnosis associated with clinical and microbiological challenges. Early recognition and treatment is required to prevent joint destruction.

Structure of the cold-shock domain protein from Neisseria meningitidis reveals a strand-exchanged dimer

Energy Technology Data Exchange (ETDEWEB)

Ren, Jingshan [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Nettleship, Joanne E.; Sainsbury, Sarah [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Saunders, Nigel J. [Bacterial Pathogenesis and Functional Genomics Group, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Owens, Raymond J., E-mail: ray@strubi.ox.ac.uk [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom)

2008-04-01

The X-ray crystal structure of the cold-shock domain protein from N. meningitidis reveals a strand-exchanged dimer. The structure of the cold-shock domain protein from Neisseria meningitidis has been solved to 2.6 Å resolution and shown to comprise a dimer formed by the exchange of two β-strands between protein monomers. The overall fold of the monomer closely resembles those of other bacterial cold-shock proteins. The neisserial protein behaved as a monomer in solution and was shown to bind to a hexathymidine oligonucleotide with a stoichiometry of 1:1 and a K{sub d} of 1.25 µM.

Resurgence of Neisseria meningitidis serogroup W ST-11 (cc11) in Madagascar, 2015-2016.

Science.gov (United States)

Rasoanandrasana, Saïda; Raberahona, Mihaja; Milenkov, Milen; Rakotomahefa Narison, Mbolanirina Lala; Ranaivo Rabetokotany, Felana; Rakotovao, Luc; Randria, Mamy Jean de Dieu; Hong, Eva; Paranhos-Baccalà, Glaucia; Taha, Muhamed-Kheir; Rakoto-Andrianarivelo, Mala

2017-02-01

The resurgence of invasive meningococcal disease caused by Neisseria meningitidis serogroup W with sequence type ST-11 (cc11) was observed in Madagascar in 2015-2016. Three cases were investigated in this study. Molecular characterization of the strains suggests the local transmission of a single genotype that may have been circulating for years. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Large Cluster of Neisseria meningitidis Urethritis in Columbus, Ohio, 2015.

Science.gov (United States)

Bazan, Jose A; Turner, Abigail Norris; Kirkcaldy, Robert D; Retchless, Adam C; Kretz, Cecilia B; Briere, Elizabeth; Tzeng, Yih-Ling; Stephens, David S; Maierhofer, Courtney; Del Rio, Carlos; Abrams, A Jeanine; Trees, David L; Ervin, Melissa; Licon, Denisse B; Fields, Karen S; Roberts, Mysheika Williams; Dennison, Amanda; Wang, Xin

2017-07-01

Neisseria meningitidis (Nm) is a Gram-negative diplococcus that normally colonizes the nasopharynx and rarely infects the urogenital tract. On Gram stain of urethral exudates, Nm can be misidentified as the more common sexually transmitted pathogen Neisseria gonorrhoeae. In response to a large increase in cases of Nm urethritis identified among men presenting for screening at a sexually transmitted disease clinic in Columbus, Ohio, we investigated the epidemiologic characteristics of men with Nm urethritis and the molecular and phylogenetic characteristics of their Nm isolates. The study was conducted between 1 January and 18 November 2015. Seventy-five Nm urethritis cases were confirmed by biochemical and polymerase chain reaction testing. Men with Nm urethritis were a median age of 31 years (interquartile range [IQR] = 24-38) and had a median of 2 sex partners in the last 3 months (IQR = 1-3). Nm cases were predominantly black (81%) and heterosexual (99%). Most had urethral discharge (91%), reported oral sex with a female in the last 12 months (96%), and were treated with a ceftriaxone-based regimen (95%). A minority (15%) also had urethral chlamydia coinfection. All urethral Nm isolates were nongroupable, ST-11 clonal complex (cc11), ET-15, and clustered together phylogenetically. Urethral Nm isolates were similar by fine typing (PorA P1.5-1,10-8, PorB 2-2, FetA F3-6), except 2, which had different PorB types (2-78 and 2-52). Between January and November 2015, 75 urethritis cases due to a distinct Nm clade occurred among primarily black, heterosexual men in Columbus, Ohio. Future urogenital Nm infection studies should focus on pathogenesis and modes of sexual transmission. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Comparison of dot-ELISA and standard ELISA for detection of Neisseria meningitidis outer membrane complex-specific antibodies

Directory of Open Access Journals (Sweden)

Elza FT Belo

Full Text Available Dot-ELISA using the outer membrane complex antigens of Neisseria meningitidis as a target was standardized for rapid detection of meningococcal-specific antibodies in human serum. We investigated the level of meningococcal-specific IgG, IgA, and IgM in serum using dot-ELISA with outer membrane antigens prepared from Neisseria meningitidis serotype B:4.19:P1.15,3,7,9 (a strain isolated from a Brazilian epidemic. The dot-ELISA is based on the same principles as the standard ELISA and is useful for detection of anti-N. meningitidis B antibodies in serum of patients with meningococcal infections. For the assay, outer membrane complexes (OMCs were absorbed by nitrocellulose membrane and blocked with a 5% skim milk solution. Serum samples were drawn upon hospital admission and during convalescence from patients with meningococcal septicemia, and single samples were drawn from uninfected controls. We retrospectively examined a total of 57 serum samples: 35 from patients infected with N. meningitidis B, 12 from patients infected with Haemophilus influenzae b, and 10 from health individuals. When performed at room temperature, dot-ELISA took approximately four hours to perform, and the optimum antigen concentration was 0.42 µg per dot. The specificity of IgG, IgM, and IgA demonstrates that dot-ELISA using OMCs from N. meningitidis B as a target is suitable for serologic verification of clinically suspected meningococcal disease in patients and for titer determination of antibodies produced during different phases of natural infection. Furthermore, the sensitivity of dot-ELISA was comparable to that of standard ELISA. Overall, dot-ELISA is simple to perform, rapid, and low cost. Further validation of the test as a screening tool is required.

Representational difference analysis of Neisseria meningitidis identifies sequences that are specific for the hyper-virulent lineage III clone

NARCIS (Netherlands)

Bart, A.; Dankert, J.; van der Ende, A.

2000-01-01

Neisseria meningitidis may cause meningitis and septicemia. Since the early 1980s, an increased incidence of meningococcal disease has been caused by the lineage III clone in many countries in Europe and in New Zealand. We hypothesized that lineage III meningococci have specific DNA sequences,

fbpABC gene cluster in Neisseria meningitidis is transcribed as an operon.

Science.gov (United States)

Khun, H H; Deved, V; Wong, H; Lee, B C

2000-12-01

The neisserial fbpABC locus has been proposed to constitute a single transcriptional unit. To confirm this operonic arrangement, transcription assays using reverse transcriptase PCR amplification were conducted with Neisseria meningitidis. The presence of fbpAB and fbpBC transcripts obtained by priming cDNA synthesis with an fbpC-sequence-specific oligonucleotide indicates that fbpABC is organized as a single expression unit. The ratio of fbpA to fbpABC mRNA was approximately between 10- to 20-fold, as determined by real-time quantitative PCR.

Neisseria meningitidis presenting as acute abdomen and recurrent reactive pericarditis

Directory of Open Access Journals (Sweden)

Karolina Akinosoglou

2016-11-01

Full Text Available Meningococcal meningitis is a well established potential fatal infection characterized by fever, headache, petechial rash, and vomiting in the majority of cases. However, protean manifestations including abdominal pain, sore throat, diarrhea and cough, even though rare, should not be overlooked. Similarly, although disseminated infection could potentially involve various organ-targets, secondary immune related complications including joints or pericardium should be dealt with caution, since they remain unresponsive to appropriate antibiotic regimens. We hereby report the rare case of an otherwise healthy adult female, presenting with acute abdominal pain masking Neisseria meningitidis serotype B meningitis, later complicated with recurrent reactive pericarditis despite appropriate antibiotic treatment. There follows a review of current literature.

Rapid Laboratory Identification of Neisseria meningitidis Serogroup C as the Cause of an Outbreak - Liberia, 2017.

Science.gov (United States)

Patel, Jaymin C; George, Josiah; Vuong, Jeni; Potts, Caelin C; Bozio, Catherine; Clark, Thomas A; Thomas, Jerry; Schier, Joshua; Chang, Arthur; Waller, Jessica L; Diaz, Maureen H; Whaley, Melissa; Jenkins, Laurel T; Fuller, Serena; Williams, Desmond E; Redd, John T; Arthur, Ray R; Taweh, Fahn; Vera Walker, Yatta; Hardy, Patrick; Freeman, Maxwell; Katawera, Victoria; Gwesa, Gulu; Gbanya, Miatta Z; Clement, Peter; Kohar, Henry; Stone, Mardia; Fallah, Mosoka; Nyenswah, Tolbert; Winchell, Jonas M; Wang, Xin; McNamara, Lucy A; Dokubo, E Kainne; Fox, LeAnne M

2017-10-27

On April 25, 2017, a cluster of unexplained illness and deaths among persons who had attended a funeral during April 21-22 was reported in Sinoe County, Liberia (1). Using a broad initial case definition, 31 cases were identified, including 13 (42%) deaths. Twenty-seven cases were from Sinoe County (1), and two cases each were from Grand Bassa and Monsterrado counties, respectively. On May 5, 2017, initial multipathogen testing of specimens from four fatal cases using the Taqman Array Card (TAC) assay identified Neisseria meningitidis in all specimens. Subsequent testing using direct real-time polymerase chain reaction (PCR) confirmed N. meningitidis in 14 (58%) of 24 patients with available specimens and identified N. meningitidis serogroup C (NmC) in 13 (54%) patients. N. meningitidis was detected in specimens from 11 of the 13 patients who died; no specimens were available from the other two fatal cases. On May 16, 2017, the National Public Health Institute of Liberia and the Ministry of Health of Liberia issued a press release confirming serogroup C meningococcal disease as the cause of this outbreak in Liberia.

Structure of the P{sub II} signal transduction protein of Neisseria meningitidis at 1.85 Å resolution

Energy Technology Data Exchange (ETDEWEB)

Nichols, Charles E. [Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Sainsbury, Sarah; Berrow, Nick S.; Alderton, David [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Saunders, Nigel J. [The Bacterial Pathogenesis and Functional Genomics Group, The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Stammers, David K. [Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Owens, Raymond J., E-mail: ray@strubi.ox.ac.uk [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom)

2006-06-01

The structure of the P{sub II} signal transduction protein of N. meningitidis at 1.85 Å resolution is described. The P{sub II} signal transduction proteins GlnB and GlnK are implicated in the regulation of nitrogen assimilation in Escherichia coli and other enteric bacteria. P{sub II}-like proteins are widely distributed in bacteria, archaea and plants. In contrast to other bacteria, Neisseria are limited to a single P{sub II} protein (NMB 1995), which shows a high level of sequence identity to GlnB and GlnK from Escherichia coli (73 and 62%, respectively). The structure of the P{sub II} protein from N. meningitidis (serotype B) has been solved by molecular replacement to a resolution of 1.85 Å. Comparison of the structure with those of other P{sub II} proteins shows that the overall fold is tightly conserved across the whole population of related proteins, in particular the positions of the residues implicated in ATP binding. It is proposed that the Neisseria P{sub II} protein shares functions with GlnB/GlnK of enteric bacteria.

Effects of multi-walled carbon nanotubes (MWCNT under Neisseria meningitidis transformation process

Directory of Open Access Journals (Sweden)

Mattos Ives B

2011-11-01

Full Text Available Abstract Background This study aimed at verifying the action of multi-walled carbon nanotubes (MWCNT under the naturally transformable Neisseria meningitidis against two different DNA obtained from isogenic mutants of this microorganism, an important pathogen implicated in the genetic horizontal transfer of DNA, causing the escape of the principal vaccination measured worldwide by the capsular switching process. Materials and methods The bacterium receptor strain C2135 was cultivated and had its mutant DNA donor M2 and M6, which received a receptor strain and MWCNT at three different concentrations. The inhibition effect of DNAse on the DNA in contact with nanoparticles was evaluated. Results The results indicated an in increase in the transformation capacity of N. meninigtidis in different concentrations of MWCNT when compared with negative control without nanotubes. A final analysis of the interaction between DNA and MWCNT was carried out using Raman Spectroscopy. Conclusion These increases in the transformation capacity mediated by MWCNT, in meningococci, indicate the interaction of these particles with the virulence acquisition of these bacteria, as well as with the increase in the vaccination escape process.

Enfermedad por meningococo, Neisseria meningitidis: perspectiva epidemiológica, clínica y preventiva Meningococcal disease caused by Neisseria meningitidis: epidemiological, clinical, and preventive perspectives

Directory of Open Access Journals (Sweden)

Lourdes Almeida-González

2004-10-01

Full Text Available La meningitis bacteriana continúa siendo uno de los grandes problemas de la salud pública mundial. En particular, la infección por Neisseria meningitidis afecta tanto a países desarrollados como subdesarrollados, y se presenta en formas endémicas y epidémicas. La enfermedad meningocóccica se puede manifestar clínicamente no sólo como meningitis, sino con cuadros fulminantes de meningococcemia. La persistencia de N. meningitidis se debe al gran porcentaje de portadores y a la dinámica de transmisión de la bacteria. Aproximadamente 500 millones de personas en el mundo son portadoras de N. meningitidis en la nasofaringe. Los factores de transmisiblidad identificados han sido el tabaquismo activo o pasivo, la presencia de infecciones virales del tracto respiratorio superior, épocas de sequía, y el hacinamiento. Por lo anterior, se han descrito brotes de enfermedad meningocóccica en cuarteles militares, escuelas, cárceles y dormitorios. Algunos determinantes que permiten la invasión sistémica incluyen daños en la mucosa nasofaríngea de portadores, cepas virulentas con formación de cápsula, ausencia de anticuerpos bactericidas y deficiencias del sistema del complemento. El control de la enfermedad meningocóccica en circunstancias endémicas y epidémicas se logra por el tratamiento de casos con antibióticos adecuados (penicilina, ceftriaxona o cloranfenicol, la quimioprofilaxis de contactos cercanos (ciprofloxacina, rifampicina o ceftriaxona, y la vigilancia clínica de éstos. Sin embargo, es fundamental subrayar que la clave para el control efectivo de la enfermedad meningocóccica es la inmunoprofilaxis. Las vacunas disponibles incluyen las de polisacáridos monovalentes o bivalentes (serogrupos A y C, tetravalentes (A, C, Y, W-135, la conjugada (C o la combinada de proteínas de membrana celular y polisacárido (B y C. Recientemente nos hemos visto forzados a establecer planes nacionales de respuesta que incluyen la

IgA1 antibodies specific for outer membrane protein PorA modulate the interaction between Neisseria meningitidis and the epithelium

NARCIS (Netherlands)

Horton, R. E.; Vidarsson, G.; Virji, M.; Williams, N. A.; Heyderman, R. S.

2009-01-01

Despite high carriage rates of Neisseria meningitidis, incidence of meningococcal disease remains low, partially due to development of natural immunity. We have previously demonstrated an inverse relationship between salivary anti-meningococcal IgA and disease incidence, but little is known about

Enfoques mucosales en vacunologia de Neisseria

Directory of Open Access Journals (Sweden)

Pérez O

2009-08-01

Full Text Available Meningococcal B strains accounts for some 72% and 28% of meningococcal diseases in infants and toddlers in Europe and the USA, respectively. Nevertheless, meningococcal diseases are rare in Cuba owing to the wide spread program on antimeningococcal vaccination in the country. Finlay Institute is one of the pioneering organizations in Neisseria Vaccinology mainly by its contribution to N. meningitidis serogroup B outer membrane-based bivalent vaccine, VA-MENGOC-BC™. This vaccine was given intramuscularly in more than 60 million doses corresponding 10.7 millions of them to Cuban young adults, children, and infants. However, most dangerous or commensally Neisseria strains enter and establish in the mucosa, where the secretory (S IgA is the main specific guardian and is mainly induced by mucosal routes. However, few mucosal vaccines exist principally due to the absent of mucosal adjuvants. We develop a Finlay Adjuvant (AF platform based in outer membrane vesicles (Proteoliposome, PL and its derivate Cochleate (Co. AFPL1 derived from serogroup B N. meningitidis is a potent Th1/CTL driving parenteral adjuvant. AFCo1 is a potent mucosal adjuvant. Therefore, we sought to go deeper in the possible mucosal cross recognition between N. meningitidis serogroups and Neisseria species and explore a concurrent mucosal and parenteral immunization strategy (SinTimVaS in order to develop suitable mucosal vaccines. Experiments were conducted in Balb/c or C57Bl6 mice with mucosal and systemic immunization using AFCo1 and AFPL1. Human sera and saliva were also analyzed for cross cognition. Mucosal cross recognition at SIgA level in human saliva between N. meningitidis serogroups B, A, C, Y, and W135 were observed. This SIgA cross recognition response was also observed between pathogenic (N. meningitidis serogroup B, N. gonorrhoeae and non-pathogenic strains (N. flava, N. lactamica. The possible influence of meningococcal vaccination against Gonorrhea was also

Crystal structure of the iron-regulated outer membrane lipoprotein FrpD (NMB0584) from Neisseria meningitidis

Czech Academy of Sciences Publication Activity Database

Sviridova, E.; Bumba, Ladislav; Řezáčová, Pavlína; Šebo, Peter; Kutá-Smatanová, Ivana

2012-01-01

Roč. 12, č. 1 (2012), s. 49-49 ISSN 1210-8529. [10th Discussions in Structural Molecular Biology. 22.03.2012-24.03.2012, Nové Hrady] R&D Projects: GA ČR(CZ) GAP207/11/0717 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z60870520; CEZ:AV0Z50200510 Keywords : Neisseria meningitidis * FrpD Subject RIV: EE - Microbiology, Virology

Vigilancia de Neisseria meningitidis en Argentina, 1993-2005: distribución de serogrupos, serotipos y serosubtipos causantes de enfermedad invasiva

OpenAIRE

Chiavetta, L.; Chávez, E.; Ruzic, A.; Mollerach, M.; Regueira, M.

2007-01-01

Neisseria meningitidis es agente causal de enfermedades severas como meningitis, bacteriemia y síndrome de shock séptico. Se presenta la distribución en serogrupos, serotipos y serosubtipos de 2244 aislamientos de N. meningitidis obtenidos de cuadros de meningitis y/o meningococcemia durante el período 1993-2005 y analizados en el Laboratorio Nacional de Referencia del INEI-ANLIS "Dr. Carlos G. Malbrán". Estos aislamientos eran provenientes de 33 hospitales de todo el país, conformados en una...

Phenotypic and genotypic changes in a new clone complex of Neisseria meningitidis causing disease in The Netherlands, 1958-1990

NARCIS (Netherlands)

Scholten, R. J.; Poolman, J. T.; Valkenburg, H. A.; Bijlmer, H. A.; Dankert, J.; Caugant, D. A.

1994-01-01

To characterize the phenotypic and genotypic changes that occurred in a new clone lineage of Neisseria meningitidis (lineage III) in the Netherlands, the electrophoretic type (ET) was determined for 79 serogroup B isolates of serotype 4 or subtype P1.4 (or both) obtained between 1958 and 1990 from

Interlaboratory comparison of agar dilution and Etest methods for determining the MICs of antibiotics used in management of Neisseria meningitidis infections

NARCIS (Netherlands)

Vázquez, Julio A.; Arreaza, Luisa; Block, Colin; Ehrhard, Ingrid; Gray, Stephen J.; Heuberger, Sigrid; Hoffmann, Steen; Kriz, Paula; Nicolas, Pierre; Olcen, Per; Skoczynska, Anna; Spanjaard, Lodewijk; Stefanelli, Paola; Taha, Muhamed-Kheir; Tzanakaki, Georgina

2003-01-01

Previous studies have shown that there is considerable variation in the methods and media used to determine the susceptibility of Neisseria meningitidis to antimicrobial agents in different countries. In this study, national and regional reference laboratories used a standardized methodology to

Role of penA polymorphisms for penicillin susceptibility in Neisseria lactamica and Neisseria meningitidis.

Science.gov (United States)

Karch, André; Vogel, Ulrich; Claus, Heike

2015-10-01

In meningococci, reduced penicillin susceptibility is associated with five specific mutations in the transpeptidase region of penicillin binding protein 2 (PBP2). We showed that the same set of mutations was present in 64 of 123 Neisseria lactamica strains obtained from a carriage study (MIC range: 0.125-2.0mg/L). The PBP2 encoding penA alleles in these strains were genetically similar to those found in intermediate resistant meningococci suggesting frequent interspecies genetic exchange. Fifty-six N. lactamica isolates with mostly lower penicillin MICs (range: 0.064-0.38mg/L) exhibited only three of the five mutations. The corresponding penA alleles were unique to N. lactamica and formed a distinct genetic clade. PenA alleles with no mutations on the other hand were unique to meningococci. Under penicillin selective pressure, genetic transformation of N. lactamica penA alleles in meningococci was only possible for alleles encoding five mutations, but not for those encoding three mutations; the transfer resulted in MICs comparable to those of meningococci harboring penA alleles that encoded PBP2 with five mutations, but considerably lower than those of the corresponding N. lactamica donor strains. Due to a transformation barrier the complete N. lactamica penA could not be transformed into N. meningitidis. In summary, penicillin MICs in N. lactamica were associated with the number of mutations in the transpeptidase region of PBP2. Evidence for interspecific genetic transfer was only observed for penA alleles associated with higher MICs, suggesting that alleles encoding only three mutations in the transpeptidase region are biologically not effective in N. meningitidis. Factors other than PBP2 seem to be responsible for the high levels of penicillin resistance in N. lactamica. A reduction of penicillin susceptibility in N. meningitidis by horizontal gene transfer from N. lactamica is unlikely to happen. Copyright © 2015 Elsevier GmbH. All rights reserved.

First genome report on novel sequence types of Neisseria meningitidis: ST12777 and ST12778.

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Veeraraghavan, Balaji; Lal, Binesh; Devanga Ragupathi, Naveen Kumar; Neeravi, Iyyan Raj; Jeyaraman, Ranjith; Varghese, Rosemol; Paul, Miracle Magdalene; Baskaran, Ashtawarthani; Ranjan, Ranjini

2018-03-01

Neisseria meningitidis is an important causative agent of meningitis and/or sepsis with high morbidity and mortality. Baseline genome data on N. meningitidis, especially from developing countries such as India, are lacking. This study aimed to investigate the whole genome sequences of N. meningitidis isolates from a tertiary care centre in India. Whole-genome sequencing was performed using an Ion Torrent™ Personal Genome Machine™ (PGM) with 400-bp chemistry. Data were assembled de novo using SPAdes Genome Assembler v.5.0.0.0. Sequence annotation was performed through PATRIC, RAST and the NCBI PGAAP server. Downstream analysis of the isolates was performed using the Center for Genomic Epidemiology databases for antimicrobial resistance genes and sequence types. Virulence factors and CRISPR were analysed using the PubMLST database and CRISPRFinder, respectively. This study reports the whole genome shotgun sequences of eight N. meningitidis isolates from bloodstream infections. The genome data revealed two novel sequence types (ST12777 and ST12778), along with ST11, ST437 and ST6928. The virulence profile of the isolates matched their sequence types. All isolates were negative for plasmid-mediated resistance genes. To the best of our knowledge, this is the first report of ST11 and ST437 N. meningitidis isolates in India along with two novel sequence types (ST12777 and ST12778). These results indicate that the sequence types circulating in India are diverse and require continuous monitoring. Further studies strengthening the genome data on N. meningitidis are required to understand the prevalence, spread, exact resistance and virulence mechanisms along with serotypes. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Two Neisseria meningitidis strains with different ability to stimulate toll-like receptor 4 through the MyD88-independent pathway

DEFF Research Database (Denmark)

Mogensen, T.H.; Paludan, Søren Riis; Kilian, Mogens

2006-01-01

Neisseria meningitidis causes acute severe diseases, including sepsis and meningitis, and more benign manifestations such as chronic meningococcemia or colonization of the upper respiratory tract. The inflammatory response, which contributes to the pathogenesis of meningococcal disease......, is initiated by pattern recognition receptors, among which Toll-like receptors (TLR)s have been ascribed a particularly important role. We have previously demonstrated that N. meningitidis induce proinflammatory cytokine expression through TLR2 and TLR4. Here we characterize the molecular basis...... for differential activation of the inflammatory response by two N. meningitidis strains. This difference was due to differential ability to activate signal transduction through TLR4, as HEK293 cells expressing TLR4 produced significantly different levels of interleukin-8 in response to these strains. At the level...

Neisseria meningitidis: a neglected cause of infectious haemorrhagic fever in the amazon rainforest.

Science.gov (United States)

Barroso, David E; Silva, Luciete A

2007-12-01

Neisseria meningitidis has not been seen as a significant cause of infectious haemorrhagic fever in the Amazon inlands; most reported cases are from the city of Manaus, the capital of the State of Amazonas. This picture is sustained by the lack of reliable microbiology laboratories, the perception of the health care workers, and the difficult to reach medical assistance; thus the number of confirmed cases is even lower with no reference of the strains phenotype. We report here the investigation of a case of suspected meningococcemia and his close contacts in a rural community in the Coari Lake, up the Amazon River.

Behavioural, emotional, and post-traumatic stress problems in children and adolescents, long term after septic shock caused by Neisseria meningitidis

NARCIS (Netherlands)

Vermunt, L. C. A. C.; Buysse, C. M. P.; Joosten, K. F. M.; Hazelzet, J. A.; Verhulst, F. C.; Utens, E. M. W. J.

2008-01-01

To assess the occurrence of a wide range of behavioural, emotional, and post-traumatic stress problems in children and adolescents, long term after septic shock caused by Neisseria meningitidis (MSS). This study included 6- to 17-year-old patients who survived MSS and were admitted to the PICU of

Strong positive selection and recombination drive the antigenic variation of the PilE protein of the human pathogen Neisseria meningitidis.

Science.gov (United States)

Andrews, T Daniel; Gojobori, Takashi

2004-01-01

The PilE protein is the major component of the Neisseria meningitidis pilus, which is encoded by the pilE/pilS locus that includes an expressed gene and eight homologous silent fragments. The silent gene fragments have been shown to recombine through gene conversion with the expressed gene and thereby provide a means by which novel antigenic variants of the PilE protein can be generated. We have analyzed the evolutionary rate of the pilE gene using the nucleotide sequence of two complete pilE/pilS loci. The very high rate of evolution displayed by the PilE protein appears driven by both recombination and positive selection. Within the semivariable region of the pilE and pilS genes, recombination appears to occur within multiple small sequence blocks that lie between conserved sequence elements. Within the hypervariable region, positive selection was identified from comparison of the silent and expressed genes. The unusual gene conversion mechanism that operates at the pilE/pilS locus is a strategy employed by N. meningitidis to enhance mutation of certain regions of the PilE protein. The silent copies of the gene effectively allow "parallelized" evolution of pilE, thus enabling the encoded protein to rapidly explore a large area of sequence space in an effort to find novel antigenic variants.

Use of restriction fragment length polymorphisms to investigate strain variation within Neisseria meningitidis

Energy Technology Data Exchange (ETDEWEB)

Williams, S.D.

1989-01-01

Similarity within bacterial populations is difficult to assess due to the limited number of characters available for evaluation and the heterogeneity of bacterial species. Currently, the preferred method used to evaluate the structure of bacterial populations is multilocus enzyme electrophoresis. However, this method is extremely cumbersome and only offers an indirect measure of genetic similarities. The development of a more direct and less cumbersome method for this purpose is warranted. Restriction fragment length polymorphism analysis was evaluated as a tool for use in the study of bacterial population structures and in the epidemiology and surveillance of infectious disease. A collection of Neisseria meningitidis was available for use in the investigation of this technique. Neisseria meningitidis is the causative agent of epidemic cerebrospinal meningitis and septicemia as well as a variety of other clinical manifestations. Each isolate in the collection was defined in terms of serogroup specificity, clinical history, geographic source, and date of isolation. Forty-six strains were chosen for this study. The DNA from each strain was restricted with Pst1 and EcoR1 and electrophoresed on agarose gels. The DNA was transferred to nylon filters and hybridized with P{sup 32} labeled DNA probes. Two randomly generated probes and a gene-specific probe were used to estimate the genetic similarities between and among the strains in the study population. A total of 28 different restriction fragment migration types were detected by the probes used. Data obtained from the RFLP analysis was analyzed by cluster analysis and multivariate statistical methods. A total of 7 clones groups were detected. Two of these appear to be major clones that comprise 35% of the population.

Use of restriction fragment length polymorphisms to investigate strain variation within Neisseria meningitidis

International Nuclear Information System (INIS)

Williams, S.D.

1989-01-01

Similarity within bacterial populations is difficult to assess due to the limited number of characters available for evaluation and the heterogeneity of bacterial species. Currently, the preferred method used to evaluate the structure of bacterial populations is multilocus enzyme electrophoresis. However, this method is extremely cumbersome and only offers an indirect measure of genetic similarities. The development of a more direct and less cumbersome method for this purpose is warranted. Restriction fragment length polymorphism analysis was evaluated as a tool for use in the study of bacterial population structures and in the epidemiology and surveillance of infectious disease. A collection of Neisseria meningitidis was available for use in the investigation of this technique. Neisseria meningitidis is the causative agent of epidemic cerebrospinal meningitis and septicemia as well as a variety of other clinical manifestations. Each isolate in the collection was defined in terms of serogroup specificity, clinical history, geographic source, and date of isolation. Forty-six strains were chosen for this study. The DNA from each strain was restricted with Pst1 and EcoR1 and electrophoresed on agarose gels. The DNA was transferred to nylon filters and hybridized with P 32 labeled DNA probes. Two randomly generated probes and a gene-specific probe were used to estimate the genetic similarities between and among the strains in the study population. A total of 28 different restriction fragment migration types were detected by the probes used. Data obtained from the RFLP analysis was analyzed by cluster analysis and multivariate statistical methods. A total of 7 clones groups were detected. Two of these appear to be major clones that comprise 35% of the population

Neisseria meningitidis: a neglected cause of infectious haemorrhagic fever in the amazon rainforest

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David E. Barroso

Full Text Available Neisseria meningitidis has not been seen as a significant cause of infectious haemorrhagic fever in the Amazon inlands; most reported cases are from the city of Manaus, the capital of the State of Amazonas. This picture is sustained by the lack of reliable microbiology laboratories, the perception of the health care workers, and the difficult to reach medical assistance; thus the number of confirmed cases is even lower with no reference of the strains phenotype. We report here the investigation of a case of suspected meningococcemia and his close contacts in a rural community in the Coari Lake, up the Amazon River.

Detección de cepas de Neisseria meningitidis resistentes a rifampicina en el Uruguay Detection of rifampicin-resistant strains of Neisseria meningitidis in Uruguay

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Gabriel Pérez Giffoni

2011-12-01

Full Text Available El objetivo de este trabajo fue caracterizar fenotípica y genotípicamente dos aislamientos de Neisseria meningitidis resistentes a rifampicina relacionados con dos eventos independientes de transmisión de enfermedad meningocócica grave que se presentaron en septiembre y octubre de 2010 en Montevideo, Uruguay. Se revisó también la base de datos de la vigilancia nacional de resistencia a los antimicrobianos de los últimos 10 años, para estimar la frecuencia de la particularidad de los meningococos caracterizados. La resistencia a rifampicina se estudió por el método epsilométrico. El serotipo y serosubtipo de los aislamientos se determinaron por ELISA y la caracterización genotípica se realizó por digestión del ADN con NheI y electroforesis en gel con campo pulsátil. Ambos aislamientos eran idénticos, B:2a:P1.5, y su fenotipo no figuraba en la colección de 408 cepas de N. meningitidis aisladas en el Uruguay en los últimos 10 años, con la excepción de dos aislamientos sensibles a rifampicina. Los dos aislamientos estudiados también compartían un pulsotipo único, diferente del de otros dos aislamientos resistentes a rifampicina obtenidos en 2003 y 2007. Por lo tanto, ambos eventos de transmisión fueron causados por una única cepa resistente a rifampicina, que podría haberse introducido al país desde otras regiones o haberse originado por un cambio del serogrupo C al B, como producto de la presión selectiva ejercida por vacunas administradas a la población. Es necesario mantener y extremar la vigilancia. No obstante, en vista de que hasta el momento este tipo de hallazgo ha sido esporádico, no se justifica cambiar el fármaco antimicrobiano que se administra a los contactos para la profilaxis, a menos que se identifique un caso secundario.The objective of this study was to characterize the phenotype and genotype of two isolates of rifampicin-resistant Neisseria meningitidis associated with two independent events

[Neisseria meningitidis urethritis: Two case reports].

Science.gov (United States)

Dubois, C; Liegeon, A-L; Fabbro, C; Truchetet, F

2017-10-01

Neisseria meningitidis (NM) is a commensal bacteria present in the oropharyngeal flora that causes invasive infections. There have been rarer reports of presence in the genital region. Herein, we present two cases of acute NM urethritis. Two men aged 30 and 31years, one of whom is homosexual and seropositive for HIV infection, presented urethral discharge which was diagnosed as acute urethritis. The unit through samples indicated the presence of NM of serogroups B and C. One of the antibiotic sensitivity tests revealed intermediate susceptibility to penicillin G and to amoxicillin. The clinical presentation of acute NM urethritis is non-specific, because of which urethral samples should be taken wherever acute urethritis is suspected. NM urethritis is infrequent and primarily affects men who have sex with men (MSM). Its current increase is due to unprotected oral-genital sexual practices. Due to the emergence of resistance to NM, antibiotic susceptibility testing should be carried out routinely to ensure appropriate therapy and prophylaxis. Cases of invasive serogroup C meningococcal infections have been recorded within the MSM population with hypothetical sexual port of entry. Thus, the French High Public Health Authority recommends vaccination against meningitis C in this population. Copyright © 2017. Published by Elsevier Masson SAS.

Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005–2012 in Turkey

Science.gov (United States)

Ceyhan, Mehmet; Gürler, Nezahat; Ozsurekci, Yasemin; Keser, Melike; Aycan, Ahmet Emre; Gurbuz, Venhar; Salman, Nuran; Camcioglu, Yildiz; Dinleyici, Ener Cagri; Ozkan, Sengul; Sensoy, Gulnar; Belet, Nursen; Alhan, Emre; Hacimustafaoglu, Mustafa; Celebi, Solmaz; Uzun, Hakan; Faik Oner, Ahmet; Kurugol, Zafer; Ali Tas, Mehmet; Aygun, Denizmen; Oncel, Eda Karadag; Celik, Melda; Yasa, Olcay; Akin, Fatih; Coşkun, Yavuz

2014-01-01

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤ 18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey. PMID:25483487

The gonococcal genetic island and type IV secretion in the pathogenic Neisseria

Directory of Open Access Journals (Sweden)

Meghan E Ramsey

2011-04-01

Full Text Available Eighty percent of Neisseria gonorrhoeae strains and some Neisseria meningitidis strains encode a 57 kb gonococcal genetic island (GGI. The GGI was horizontally acquired and is inserted in the chromosome at the replication terminus. The GGI is flanked by direct repeats, and site-specific recombination at these sites results in excision of the GGI and may be responsible for its original acquisition. Although the role of the GGI in N. meningitidis is unclear, the GGI in N. gonorrhoeae encodes a type IV secretion system (T4SS. Type IV secretion systems are versatile multi-protein complexes and include both conjugation systems as well as effector systems that translocate either proteins or DNA-protein complexes. In N. gonorrhoeae, the T4SS secretes single-stranded chromosomal DNA into the extracellular milieu in a contact-independent manner. Importantly, the DNA secreted through the T4SS is effective in natural transformation and therefore contributes to the spread of genetic information through Neisseria populations. Mutagenesis experiments have identified genes for DNA secretion including those encoding putative structural components of the apparatus, peptidoglycanases which may act in assembly, and relaxosome components for processing the DNA and delivering it to the apparatus. The T4SS may also play a role in infection by N. gonorrhoeae. During intracellular infection, N. gonorrhoeae requires the Ton complex for iron acquisition and survival. However, N. gonorrhoeae strains that do not express the Ton complex can survive intracellularly if they express structural components of the T4SS. These data provide evidence that the T4SS is expressed during intracellular infection and suggest that the T4SS may provide an advantage for intracellular survival. Here we review our current understanding of how the GGI and type IV secretion affect natural transformation and pathogenesis in N. gonorrhoeae and N. meningitidis.

A Neisseria meningitidis fbpABC mutant is incapable of using nonheme iron for growth.

Science.gov (United States)

Khun, H H; Kirby, S D; Lee, B C

1998-05-01

The neisserial fbpABC locus has been proposed to act as an iron-specific ABC transporter system. To confirm this assigned function, we constructed an fbpABC mutant in Neisseria meningitidis by insertional inactivation of fbpABC with a selectable antibiotic marker. The mutant was unable to use iron supplied from human transferrin, human lactoferrin, or iron chelates. However, the use of iron from heme and human hemoglobin was unimpaired. These results support the obligatory participation of fbpABC in neisserial periplasmic iron transport and do not indicate a role for this genetic locus in the heme iron pathway.

Genetic diversity of Neisseria meningitidis serogroup C ST-4821 in China based on multiple-locus variable number tandem repeat analysis.

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Xiaoying Shan

Full Text Available Neisseria meningitidis sequence type (ST-4821 was first reported in China in 2003, and a new hyper-virulent lineage has been designated as the ST-4821 complex. A large number of N. meningitidis ST-4821 strains have been identified in China since 2003; however, the microevolution characteristics of this complex are unclear. Different combinations of variable number of tandem repeats (VNTR loci were used in multiple-locus VNTR analysis (MLVA to analyze 118 N. meningitidis serogroup C ST-4821 strains isolated from seventeen provinces between 2003 and 2012. Additionally, MLVA with five VNTR loci was performed due to its high discriminatory power. One hundred and eighteen isolates were found to comprise 112 subtypes based on MLVA, and 16 outbreak-associated strains were clustered into one group. These data indicate a high level of diversity for N. meningitidis ST-4821 due to microevolution in the last decade. In addition, the results revealed high similarity between isolates from the same geographic origins, which is helpful when monitoring the spread of N. meningitidis serogroup C ST-4821 and will provide valuable information for the control and prevention of bacterial meningitis in China.

Necrotising fasciitis as atypical presentation of infection with emerging Neisseria meningitidis serogroup W (MenW) clonal complex 11, the Netherlands, March 2017

NARCIS (Netherlands)

Russcher, Anne; Fanoy, Ewout; van Olden, Ger D. J.; Graafland, Antonie D.; van der Ende, Arie; Knol, Mirjam J.

2017-01-01

In March 2017, a patient with necrotising fasciitis caused by Neisseria meningitidis serogroup W (MenW) clonal complex 11 was diagnosed in the Netherlands. Unusual and severe presentations of MenW infections are common in the current European epidemic. In the Netherlands, the incidence of MenW

Recombinant outer membrane secretin PilQ(406-770) as a vaccine candidate for serogroup B Neisseria meningitidis.

Science.gov (United States)

Haghi, Fakhri; Peerayeh, Shahin Najar; Siadat, Seyed Davar; Zeighami, Habib

2012-02-21

Secretin PilQ is an antigenically conserved outer membrane protein which is present on most meningococci. This protein naturally expressed at high levels and is essential for meningococcal pilus expression at the cell surface. A 1095 bp fragment of C-terminal of secretin pilQ from serogroup B Neisseria meningitidis was cloned into prokaryotic expression vector pET-28a. Recombinant protein was overexpressed with IPTG and affinity-purified by Ni-NTA agarose. BALB/c mice were immunized subcutaneously with purified rPilQ(406-770) mixed with Freund's adjuvant. Serum antibody responses to serogroups A and B N. meningitidis whole cells or purified rPilQ(406-770) and functional activity of antibodies were determined by ELISA and SBA, respectively. The output of rPilQ(406-770) was approximately 50% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with PilQ(406-770) mixed with Freund's adjuvant in comparison with control groups. Antisera produced against rPilQ(406-770) demonstrated strong surface reactivity to serogroups A and B N. meningitidis tested by whole-cell ELISA. Surface reactivity to serogroup B N. meningitidis was higher than serogroup A. The sera from PilQ(406-770) immunized animals were strongly bactericidal against serogroups A and B. These results suggest that rPilQ(406-770) is a potential vaccine candidate for serogroup B N. meningitidis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Notes from the Field: Increase in Neisseria meningitidis-Associated Urethritis Among Men at Two Sentinel Clinics - Columbus, Ohio, and Oakland County, Michigan, 2015.

Science.gov (United States)

Bazan, Jose A; Peterson, Amy S; Kirkcaldy, Robert D; Briere, Elizabeth C; Maierhofer, Courtney; Turner, Abigail Norris; Licon, Denisse B; Parker, Nicole; Dennison, Amanda; Ervin, Melissa; Johnson, Laura; Weberman, Barbara; Hackert, Pamela; Wang, Xin; Kretz, Cecilia B; Abrams, A Jeanine; Trees, David L; Del Rio, Carlos; Stephens, David S; Tzeng, Yih-Ling; DiOrio, Mary; Roberts, Mysheika Williams

2016-06-03

Neisseria meningitidis (Nm) urogenital infections, although less common than infections caused by Neisseria gonorrhoeae (Ng), have been associated with urethritis, cervicitis, proctitis, and pelvic inflammatory disease. Nm can appear similar to Ng on Gram stain analysis (gram-negative intracellular diplococci) (1-5). Because Nm colonizes the nasopharynx, men who receive oral sex (fellatio) can acquire urethral Nm infections (1,3,5). This report describes an increase in Nm-associated urethritis in men attending sexual health clinics in Columbus, Ohio, and Oakland County, Michigan.

Portadores nasofaríngeos de Neisseria meningitidis en trabajadores con riesgo ocupacional

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Isabel Martínez

2010-04-01

Full Text Available Los portadores de Neisseria meningitidis constituyen la principal fuente de infección y transmisión de la enfermedad meningocócica. Conocer su prevalencia, las características de las cepas aisladas y los factores de riesgos asociados con el estado de portador, aportan datos valiosos al control y vigilancia epidemiológica de esta entidad clínica. Para cumplimentar los objetivos propuestos se realizó un estudio transversal descriptivo de portadores de N. meningitidis en 112 trabajadores de un centro de producción de biofarmacéuticos de La Habana, con edades comprendidas entre 18_60 años. Previo a su realización se cumplió con las exigencias bioéticas requeridas para este tipo de estudio. A todos se les realizó un exudado nasofaríngeo y una encuesta, donde se indagó sobre factores de riesgo (edad, sexo, hacinamiento, hábito de fumar, consumo de bebidas alcohólicas, amigdalectomía y antecedentes de infección respiratoria que favorecen la condición del portador. La identificación de las cepas de N. meningitidis se realizó según métodos convencionales, la clasificación de los serogrupos se hizo por aglutinación en láminas portaobjetos con antisueros comerciales y para la identificación de los serotipos y subtipos se empleó un ensayo inmunoenzimático (ELISA de células enteras con anticuerpos monoclonales. Se detectó un 8% de portadores de N. meningitidis con predominio del serogrupo B (77,8% y el fenotipo más frecuente fue el B:4:P1.4 (33,3%. Al analizar el estado de portador y su asociación con los factores de riesgo, la edad (p = 0,05 y el sexo (p = 0,013 mostraron diferencias significativas. Se demostró la posibilidad del riesgo ocupacional en aquellos individuos que por su profesión están en contacto con microorganismos patógenos

The structure of lactoferrin-binding protein B from Neisseria meningitidis suggests roles in iron acquisition and neutralization of host defences

Science.gov (United States)

Brooks, Cory L.; Arutyunova, Elena; Lemieux, M. Joanne

2014-01-01

Pathogens have evolved a range of mechanisms to acquire iron from the host during infection. Several Gram-negative pathogens including members of the genera Neisseria and Moraxella have evolved two-component systems that can extract iron from the host glycoproteins lactoferrin and transferrin. The homologous iron-transport systems consist of a membrane-bound transporter and an accessory lipoprotein. While the mechanism behind iron acquisition from transferrin is well understood, relatively little is known regarding how iron is extracted from lactoferrin. Here, the crystal structure of the N-terminal domain (N-lobe) of the accessory lipoprotein lactoferrin-binding protein B (LbpB) from the pathogen Neisseria meningitidis is reported. The structure is highly homologous to the previously determined structures of the accessory lipoprotein transferrin-binding protein B (TbpB) and LbpB from the bovine pathogen Moraxella bovis. Docking the LbpB structure with lactoferrin reveals extensive binding interactions with the N1 subdomain of lactoferrin. The nature of the interaction precludes apolactoferrin from binding LbpB, ensuring the specificity of iron-loaded lactoferrin. The specificity of LbpB safeguards proper delivery of iron-bound lactoferrin to the transporter lactoferrin-binding protein A (LbpA). The structure also reveals a possible secondary role for LbpB in protecting the bacteria from host defences. Following proteolytic digestion of lactoferrin, a cationic peptide derived from the N-terminus is released. This peptide, called lactoferricin, exhibits potent antimicrobial effects. The docked model of LbpB with lactoferrin reveals that LbpB interacts extensively with the N-terminal lactoferricin region. This may provide a venue for preventing the production of the peptide by proteolysis, or directly sequestering the peptide, protecting the bacteria from the toxic effects of lactoferricin. PMID:25286931

SENSITIVITAS KUMAN NEISSERIA MENINGITIDIS YANG DIISOLASI DARI JAMAAH HAJI INDONESIA TERHADAP BEBERAPA ANTIBIOTIK

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Muljati Prijanto

2012-09-01

Full Text Available The meningitis meningococcal disease caused by Neisseriae meningitidis is an infection of meninges and cerebrospinal fluid (CSF of the brain and the spinal cord. N. meningitidis is classified into 13 serogroups based on the immunologic reactivity of the capsular polysaccharide. Since 1993 the number of cases and carriers of haj pilgrims from Indonesia have increased. In 1996 the carrier rate was 9,4%, and case fatality rate of Indonesian haj pilgrims in Saudi Arabia was 71,4%. The dominant serogroup was serogroup B. The meningitis vaccine of serogroup B is not available yet. Until now there is not enough information of the laboratory results from the hospital in Saudi Arabia, regarding the strain that caused the infection of haj pilgrims from Indonesia. To prevent transmission of the disease among Haj pilgrims, since 1997, chemoprophylaxis with ciprofloxacine has been given to close contact persons of haj pilgrim patient. The objectives of this study are: First, to know the effectiveness of ciprofloxacin in decreasing the carrier rate of meningitis meningococcus in haj pilgrims. Second, to identify the serogroup of N. meningitidis isolated from carrier or patient and thirdly to know the sensitivity of bacteria to several antibiotics recommended by WHO. Nasofaringeal swabs were taken from 914 haj pilgrims from group of contact person of cases or suspected cases and 311 haj pilgrims from control group at embarkation in Jakarta. Ciprofloxacin was given to the study group in Saudi Arabia. Isolation and serogrouping were carried out for serogroup A, B, C. The result shows that the effectiveness of ciprofloxacin to N. meningitidis in the treated group were 98.58% and control were 85.54%, respectively. The serogroup of N. meningitidis is isolated from 13 carriers of treated group 69,23% could not be classified as serogroup A, B, or C. In the control group, 45 isolated strains from carriers consist of serogroup B 40%, serogroup C 28,9%, serogroup A 20

Structural and Biochemical Characterization of the Oxidoreductase NmDsbA3 from Neisseria meningitidis

Energy Technology Data Exchange (ETDEWEB)

Vivian, Julian P.; Scoullar, Jessica; Robertson, Amy L.; Bottomley, Stephen P.; Horne, James; Chin, Yanni; Wielens, Jerome; Thompson, Philip E.; Velkov, Tony; Piek, Susannah; Byres, Emma; Beddoe, Travis; Wilce, Matthew C.J.; Kahler, Charlene M.; Rossjohn, Jamie; Scanlon, Martin J. (UWA); (Monash)

2009-09-02

DsbA is an enzyme found in the periplasm of Gram-negative bacteria that catalyzes the formation of disulfide bonds in a diverse array of protein substrates, many of which are involved in bacterial pathogenesis. Although most bacteria possess only a single essential DsbA, Neisseria meningitidis is unusual in that it possesses three DsbAs, although the reason for this additional redundancy is unclear. Two of these N. meningitidis enzymes (NmDsbA1 and NmDsbA2) play an important role in meningococcal attachment to human epithelial cells, whereas NmDsbA3 is considered to have a narrow substrate repertoire. To begin to address the role of DsbAs in the pathogenesis of N. meningitidis, we have determined the structure of NmDsbA3 to 2.3-{angstrom} resolution. Although the sequence identity between NmDsbA3 and other DsbAs is low, the NmDsbA3 structure adopted a DsbA-like fold. Consistent with this finding, we demonstrated that NmDsbA3 acts as a thiol-disulfide oxidoreductase in vitro and is reoxidized by Escherichia coli DsbB (EcDsbB). However, pronounced differences in the structures between DsbA3 and EcDsbA, which are clustered around the active site of the enzyme, suggested a structural basis for the unusual substrate specificity that is observed for NmDsbA3.

Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB

Energy Technology Data Exchange (ETDEWEB)

Tanabe, Mikio; Nimigean, Crina M.; Iverson, T.M. (Weill-Med); (Vanderbilt)

2010-06-25

PorB is the second most prevalent outer membrane protein in Neisseria meningitidis. PorB is required for neisserial pathogenesis and can elicit a Toll-like receptor mediated host immune response. Here, the x-ray crystal structure of PorB has been determined to 2.3 {angstrom} resolution. Structural analysis and cocrystallization studies identify three putative solute translocation pathways through the channel pore: One pathway transports anions nonselectively, one transports cations nonselectively, and one facilitates the specific uptake of sugars. During infection, PorB likely binds host mitochondrial ATP, and cocrystallization with the ATP analog AMP-PNP suggests that binding of nucleotides regulates these translocation pathways both by partial occlusion of the pore and by restricting the motion of a putative voltage gating loop. PorB is located on the surface of N. meningitidis and can be recognized by receptors of the host innate immune system. Features of PorB suggest that Toll-like receptor mediated recognition outer membrane proteins may be initiated with a nonspecific electrostatic attraction.

A probable prehistoric case of meningococcal disease from San Francisco Bay: Next generation sequencing of Neisseria meningitidis from dental calculus and osteological evidence.

Science.gov (United States)

Eerkens, Jelmer W; Nichols, Ruth V; Murray, Gemma G R; Perez, Katherine; Murga, Engel; Kaijankoski, Phil; Rosenthal, Jeffrey S; Engbring, Laurel; Shapiro, Beth

2018-05-25

Next Generation Sequencing (NGS) of ancient dental calculus samples from a prehistoric site in San Francisco Bay, CA-SCL-919, reveals a wide range of potentially pathogenic bacteria. One older adult woman, in particular, had high levels of Neisseria meningitidis and low levels of Haemophilus influenzae, species that were not observed in the calculus from three other individuals. Combined with the presence of incipient endocranial lesions and pronounced meningeal grooves, we interpret this as an ancient case of meningococcal disease. This disease afflicts millions around the globe today, but little is known about its (pre)history. With additional sampling, we suggest NGS of calculus offers an exciting new window into the evolutionary history of these bacterial species and their interactions with humans. Copyright © 2018 Elsevier Inc. All rights reserved.

Host iron binding proteins acting as niche indicators for Neisseria meningitidis.

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Philip W Jordan

Full Text Available Neisseria meningitidis requires iron, and in the absence of iron alters its gene expression to increase iron acquisition and to make the best use of the iron it has. During different stages of colonization and infection available iron sources differ, particularly the host iron-binding proteins haemoglobin, transferrin, and lactoferrin. This study compared the transcriptional responses of N. meningitidis, when grown in the presence of these iron donors and ferric iron, using microarrays.Specific transcriptional responses to the different iron sources were observed, including genes that are not part of the response to iron restriction. Comparisons between growth on haemoglobin and either transferrin or lactoferrin identified changes in 124 and 114 genes, respectively, and 33 genes differed between growth on transferrin or lactoferrin. Comparison of gene expression from growth on haemoglobin or ferric iron showed that transcription is also affected by the entry of either haem or ferric iron into the cytoplasm. This is consistent with a model in which N. meningitidis uses the relative availability of host iron donor proteins as niche indicators.Growth in the presence of haemoglobin is associated with a response likely to be adaptive to survival within the bloodstream, which is supported by serum killing assays that indicate growth on haemoglobin significantly increases survival, and the response to lactoferrin is associated with increased expression of epithelial cell adhesins and oxidative stress response molecules. The transferrin receptor is the most highly transcribed receptor and has the fewest genes specifically induced in its presence, suggesting this is the favoured iron source for the bacterium. Most strikingly, the responses to haemoglobin, which is associated with unrestricted growth, indicates a low iron transcriptional profile, associated with an aggressive phenotype that may be adaptive to access host iron sources but which may also

Meningococcal disease in The Netherlands, 1958-1990: a steady increase in the incidence since 1982 partially caused by new serotypes and subtypes of Neisseria meningitidis

NARCIS (Netherlands)

Scholten, R. J.; Bijlmer, H. A.; Poolman, J. T.; Kuipers, B.; Caugant, D. A.; van Alphen, L.; Dankert, J.; Valkenburg, H. A.

1993-01-01

In order to explain a threefold increase in the incidence of meningococcal disease in the Netherlands during the 1980s, we serotyped and subtyped Neisseria meningitidis isolates recovered between 1958 and 1990 from > 3,000 patients with systemic disease. No single strain could be held responsible

Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

Science.gov (United States)

Abdeldaim, Guma M K; Strålin, Kristoffer; Korsgaard, Jens; Blomberg, Jonas; Welinder-Olsson, Christina; Herrmann, Björn

2010-12-03

Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR) for detection of S. pneumoniae (9802 gene fragment), H. influenzae (omp P6 gene) and N. meningitidis (ctrA gene). The method was evaluated on bronchoalveolar lavage (BAL) samples from 156 adults with lower respiratory tract infection (LRTI) and 31 controls, and on 87 cerebrospinal fluid (CSF) samples from meningitis patients. The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis) in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 10⁵ genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively.In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both bacteria. The PCR provides increased

Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis

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Welinder-Olsson Christina

2010-12-01

Full Text Available Abstract Background Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR for detection of S. pneumoniae (9802 gene fragment, H. influenzae (omp P6 gene and N. meningitidis (ctrA gene. The method was evaluated on bronchoalveolar lavage (BAL samples from 156 adults with lower respiratory tract infection (LRTI and 31 controls, and on 87 cerebrospinal fluid (CSF samples from meningitis patients. Results The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 105 genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively. In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both

Use of sodC versus ctrA for real-time polymerase chain reaction-based detection of Neisseria meningitidis in sterile body fluids

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Fábio Takenori Higa

2013-04-01

Full Text Available We evaluated the use of a newly described sodC-based real-time-polymerase chain reaction (RT-PCR assay for detecting Neisseria meningitidis in normally sterile sites, such as cerebrospinal fluid and serum. The sodC-based RT-PCR assay has an advantage over ctrA for detecting nongroupable N. meningitidis isolates, which are commonly present in asymptomatic pharyngeal carriage. However, in our study, sodC-based RT-PCR was 7.5% less sensitive than ctrA. Given the public health impact of possible false-negative results due to the use of the sodC target gene alone, sodC-based RT-PCR for the diagnosis of meningococcal meningitis should be used with caution.

The role of glyceraldehyde 3-phosphate dehydrogenase (GapA-1 in Neisseria meningitidis adherence to human cells

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Wooldridge Karl G

2010-11-01

Full Text Available Abstract Background Glyceraldehyde 3-phosphate dehydrogenases (GAPDHs are cytoplasmic glycolytic enzymes, which although lacking identifiable secretion signals, have also been found localized to the surface of several bacteria (and some eukaryotic organisms; where in some cases they have been shown to contribute to the colonization and invasion of host tissues. Neisseria meningitidis is an obligate human nasopharyngeal commensal which can cause life-threatening infections including septicaemia and meningitis. N. meningitidis has two genes, gapA-1 and gapA-2, encoding GAPDH enzymes. GapA-1 has previously been shown to be up-regulated on bacterial contact with host epithelial cells and is accessible to antibodies on the surface of capsule-permeabilized meningococcal cells. The aims of this study were: 1 to determine whether GapA-1 was expressed across different strains of N. meningitidis; 2 to determine whether GapA-1 surface accessibility to antibodies was dependant on the presence of capsule; 3 to determine whether GapA-1 can influence the interaction of meningococci and host cells, particularly in the key stages of adhesion and invasion. Results In this study, expression of GapA-1 was shown to be well conserved across diverse isolates of Neisseria species. Flow cytometry confirmed that GapA-1 could be detected on the cell surface, but only in a siaD-knockout (capsule-deficient background, suggesting that GapA-1 is inaccessible to antibody in in vitro-grown encapsulated meningococci. The role of GapA-1 in meningococcal pathogenesis was addressed by mutational analysis and functional complementation. Loss of GapA-1 did not affect the growth of the bacterium in vitro. However, a GapA-1 deficient mutant showed a significant reduction in adhesion to human epithelial and endothelial cells compared to the wild-type and complemented mutant. A similar reduction in adhesion levels was also apparent between a siaD-deficient meningococcal strain and an

Immunogenicity of recombinant class 1 protein from Neisseria meningitidis refolded into phospholipid vesicles and detergent.

Science.gov (United States)

Niebla, O; Alvarez, A; Martín, A; Rodríguez, A; Delgado, M; Falcón, V; Guillén, G

2001-05-14

The possibility of eliciting bactericidal antibodies against a recombinant class 1 protein (P1) from Neisseria meningitidis, joined to the first 45 amino acids of the neisserial LpdA protein (PM82), was examined. P1 was produced in Escherichia coli as intracellular inclusion bodies, from which it was purified and reconstituted by (a) inclusion into phospholipid vesicles and detergent and (b) refolding in 0.1% SDS. When Balb/c mice were immunised, high titres of subtype-specific bactericidal antibodies against P1 were obtained in both cases. These results suggest that in spite of being a denaturing agent, it is possible to use SDS to reconstitute the P1 protein in a conformation that exposes the immunodominat regions.

Intercontinental spread of a genetically distinctive complex of clones of Neisseria meningitidis causing epidemic disease.

Science.gov (United States)

Caugant, D A; Frøholm, L O; Bøvre, K; Holten, E; Frasch, C E; Mocca, L F; Zollinger, W D; Selander, R K

1986-07-01

Strains of Neisseria meningitidis responsible for an epidemic of meningococcal disease occurring in Norway since the mid-1970s and for recent increases in the incidence of disease in several other parts of Europe have been identified by multilocus enzyme electrophoresis as members of a distinctive group of 22 closely related clones (the ET-5 complex). Clones of this complex have also colonized South Africa, Chile, Cuba, and Florida, where they have been identified as the causative agents of recent outbreaks of meningococcal disease. There is strong circumstantial evidence that outbreaks of disease occurring in Miami in 1981 and 1982 were caused in large part by bacteria that reached Florida via human immigrants from Cuba.

Asymtomatic carriage of Neisseria meningitidis and Neisseria lactamica in relation to Streptococcus pneumoniae and Haemophilus influenzae colonization in healthy children: Apropos of 1400 children sampled

International Nuclear Information System (INIS)

Bakir, Mustafa; Yagci, Aysegul; Ulger, Nurver; Akbenlioglu, Cengiz; Ilki, Arzu; Soyletir, Guner

2001-01-01

Meningococcal disease is one of the most important causes of morbidity and mortality among children in many parts of the world. Main reservoir of carriage and site of meningococcal dissemination appears to be the upper respiratory tract. Colonization of Neisseria meningitidis and lactamica and factors affecting this carriage were determined in a group of healthy children aged 0-10 years. Meningococcus and N. lactamica carriage were detected in 17 (1.23%) and 245 (17.7%) of 1382 subjects, respectively. Number (%) of serogroups for meningococci was 1 (6), 5 (29), 0 (0), 1 (6), 1 (6), and 9 (53) for A, B, C, D, W135, and Y, respectively. Having more than three household members, elementary school attendance, pharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae were associated with carriage of meningococci, whereas age less than 24-month was associated with carriage of N. lactamica. There was a reverse carriage rate between N. meningitidis and N. lactamica by age which may suggest a possible protective role of N. lactamica against meningococcal colonization among pre-school children

Nasopharyngeal Carriage Rate and Serogroups of Neisseria meningitidis in Turkish recruits upon entry to the military

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Ahmet Basustaoglu

2011-08-01

Full Text Available Aim: The aim of this study was to determine nasopharyngeal carriage rate and serogroup of Neisseria meningitidis strains isolated from Turkish recruits upon entry to the military. Material and Methods: Nasopharyngeal swab samples were obtained from 1995 soldiers and were inoculated immediately on BBL-modified Thayer-Martin medium plates. The plates were examined for the presence of colonies showing the typical morphology of N. meningitidis. Suspect colonies were screened for oxidase reactivity, and positive colonies were Gram stained. If Gram-negative diplococci were present, a biochemical profile by the API NH system was used for confirmation. Serogrouping of the meningococcal isolates was performed by a slide agglutination technique. Findings: The nasopharyngeal carriage rate of N. meningitidis was found to be 4.2% (n=83. Of these meningococci, 15.6% (n=13 were serogroup Y, 10.8% (n=9 were serogroup W-135, 9.6% (n=8 were serogroup C, 6.1% (n=5 were serogroup B, 2.4% (n=2 were serogroup A. The 46 isolates (55.4% were detected as nonserogroupable. Conclusion: Since serogroup Y and W-135 are predominant in this study population, it was suggest that Turkish recruits should be vaccinated by quadrivalent vaccine (A,C,Y, and W-135 upon the military instead of A+C polysaccharide vaccine and now quadrivalent vaccine has been carried out. [TAF Prev Med Bull 2011; 10(4.000: 447-450

Inhibition of the dapE-Encoded N-Succinyl-L,L-diaminopimelic Acid Desuccinylase from Neisseria meningitidis by L-Captopril

OpenAIRE

Starus, Anna; Nocek, Boguslaw; Bennett, Brian; Larrabee, James A.; Shaw, Daniel L.; Sae-Lee, Wisath; Russo, Marie T.; Gillner, Danuta M.; Makowska-Grzyska, Magdalena; Joachimiak, Andrzej; Holz, Richard C.

2015-01-01

Binding of the competitive inhibitor L-captopril to the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Neisseria meningitidis (NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods. L-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE) with an IC50 of 3.3 μM and a measured Ki of 1.8 μM and displayed a dose-responsive antibiotic activity toward Esch...

Carrier state of Haemophilus influenzae type b (Hib, Streptococcus pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children in Pokhara, Nepal

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Dharm Raj Bhatta

2014-02-01

Full Text Available Objective: To determine the incidence of carrier state of Haemophilus influenzae type b, Streptococcus pneumoniae (S. pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children. Methods: Specimen from posterior pharyngeal wall and tonsils were collected on calcium alginate coated swabs from 1 02 participants. Processing of specimen and antimicrobial susceptibility testing was done by standard procedures. Results: Potential pathogens isolated in our study were S. pneumoniae (14.7%, Staphylococcus aureus (12.7%, Corynebacterium diphtheriae (3.9%, Streptococcus pyogenes (3.9% and Haemophilus influenzae (1.9%. Important findings in antibiogram include high resistance of S. pneumoniae to penicillin (73% and resistance of Staphylococcus aureus to oxacillin (23%. Conclusions: Pharyngeal colonization by S. pneumoniae among school children was found high and there is need of introduction of pneumococcal vaccines among children. Despite expected universal vaccination, pharyngeal colonization by Corynebacterium diphtheriae is possible and there is possibility of transmission.

Pneumonia caused by Neisseria meningitidis: report of a case and review of the literature

International Nuclear Information System (INIS)

Acosta M, Rafael E; Rada E, Robin A

2010-01-01

Pneumonia caused by Neisseria meningitidis, a gram-negative diplococcus affecting only humans, is a rare disease that was first recognized more than 60 years ago. The infection is usually manifested as meningitis and septicemia with cutaneous manifestations. Involvement of the lower respiratory tract is much less frequently diagnosed, partly because this microorganism can be present in the oropharyngeal flora of up to 10% of asymptomatic people. The serotypes most frequently involved in lung infections are: B, Y, and W-135. Serotype Y has been held to be most important. In cases of pneumonia, diagnosis has to be reached by isolation of the microorganism in blood and/or pleural fluid. Mortality is low, and person-to-person transmission, although documented, is rare. Complications such as pulmonary abscess, pleural effusion, and pericarditis are infrequent.

Adjuvantes:Un componente esencial de las vacunas de Neisseria

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Reinaldo Acevedo

2009-08-01

Full Text Available Adjuvants may be classified into delivery systems and immune potentiator or modulator molecules based on their mechanism of action. Neisseria vaccines containing traditional adjuvants such as aluminium salts have existed for long time, but meningitis caused by Neisseria meningitidis serogroups, particularly serogroup B, continues to be a global health problem. Novel strategies have applied in silico and recombinant technologies to develop "universal" antigens (e.g. proteins, peptides and plasmid DNA for vaccines, but these antigens have been shown to be poorly immunogenic even when alum adjuvanted, implying a need for better vaccine design. In this work we review the use of natural, detoxified, or synthetic molecules in combination with antigens to activate the innate immune system and to modulate the adaptive immune responses. In the main, antigenic and imune potentiator signals are delivered using nano-, micro-particles, alum, or emulsions. The importance of interaction between adjuvants and antigens to activate and target dendritic cells, the bridge between the innate and adaptive immune systems, will be discussed. In addition, nasal vaccine strategies based on the development of mucosal adjuvants and Neisseria derivatives to eliminate the pathogen at the site of infection provide promising adjuvants effective not only against respiratory pathogens, but also against pathogens responsible for enteric and sexually transmitted diseases.

A virulence-associated filamentous bacteriophage of Neisseria meningitidis increases host-cell colonisation.

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Emmanuelle Bille

2017-07-01

Full Text Available Neisseria meningitidis is a commensal of human nasopharynx. In some circumstances, this bacteria can invade the bloodstream and, after crossing the blood brain barrier, the meninges. A filamentous phage, designated MDAΦ for Meningococcal Disease Associated, has been associated with invasive disease. In this work we show that the prophage is not associated with a higher virulence during the bloodstream phase of the disease. However, looking at the interaction of N. meningitidis with epithelial cells, a step essential for colonization of the nasopharynx, we demonstrate that the presence of the prophage, via the production of viruses, increases colonization of encapsulated meningococci onto monolayers of epithelial cells. The analysis of the biomass covering the epithelial cells revealed that meningococci are bound to the apical surface of host cells by few layers of heavily piliated bacteria, whereas, in the upper layers, bacteria are non-piliated but surrounded by phage particles which (i form bundles of filaments, and/or (ii are in some places associated with bacteria. The latter are likely to correspond to growing bacteriophages during their extrusion through the outer membrane. These data suggest that, as the biomass increases, the loss of piliation in the upper layers of the biomass does not allow type IV pilus bacterial aggregation, but is compensated by a large production of phage particles that promote bacterial aggregation via the formation of bundles of phage filaments linked to the bacterial cell walls. We propose that MDAΦ by increasing bacterial colonization in the mucosa at the site-of-entry, increase the occurrence of diseases.

Vigilancia de Neisseria meningitidis en Argentina, 1993-2005: distribución de serogrupos, serotipos y serosubtipos causantes de enfermedad invasiva Surveillance of Neisseria meningitidis in Argentina, 1993-2005: Distribution of serogroups, serotypes and serosubtypes isolated from invasive disease

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L. Chiavetta

2007-03-01

Full Text Available Neisseria meningitidis es agente causal de enfermedades severas como meningitis, bacteriemia y síndrome de shock séptico. Se presenta la distribución en serogrupos, serotipos y serosubtipos de 2244 aislamientos de N. meningitidis obtenidos de cuadros de meningitis y/o meningococcemia durante el período 1993-2005 y analizados en el Laboratorio Nacional de Referencia del INEI-ANLIS "Dr. Carlos G. Malbrán". Estos aislamientos eran provenientes de 33 hospitales de todo el país, conformados en una red nacional de laboratorios para el estudio de meningitis bacteriana. Durante el período 1993-1995 prevaleció el serogrupo B (66%, mientras que entre los años 1995 y 2001 prevaleció el serogrupo C (65%; a partir de esta fecha se restableció la prevalencia de B. En los últimos 5 años los serogrupos Y y W135 representaron en su conjunto el 15,6%, mientras que hasta el año 2000 no superaron el 4,7%. Se registró mayor diversidad en la distribución de serotipos y serosubtipos dentro del serogrupo B que dentro del serogrupo C. Los aislamientos no subtipables durante todo el período de estudio representaron el 52,8%; este elevado porcentaje evidencia la limitada capacidad de la serología para la determinación de subtipos de meningococo.Neisseria meningitidis is an important cause of meningitis, bacteremia and septic shock syndrome. We herein present the distribution of serogroups, serotypes and serosubtypes of 2244 isolates of N. meningitidis from patients with meningitis or meningococcemia, received within the period 1993-2005, in the National Reference Laboratory, INEI-ANLIS "Dr. Carlos G. Malbrán", from 33 Argentine hospitals that are included in a National Network devoted to for the study of bacterial meningitis. Between 1993-1995, serogroup B was prevalent (66% whereas in the period from 1995-2001, serogroup C prevailed (65%. However, following but after that period, the prevalence of serogroup B was recovered. In the last 5 years of the

Antigen sequence typing of outer membrane protein (fetA gene of Neisseria meningitidis serogroup A from Delhi & adjoining areas

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S Dwivedi

2014-01-01

Full Text Available Background & objectives: Meningitis caused by Neisseria meningitidis is a fatal disease. Meningococcal meningitis is an endemic disease in Delhi and irregular pattern of outbreaks has been reported in India. All these outbreaks were associated with serogroup A. Detailed molecular characterization of N. meningitidis is required for the management of this fatal disease. In this study, we characterized antigenic diversity of surface exposed outer membrane protein (OMP FetA antigen of N. meningitidis serogroup A isolates obtained from cases of invasive meningococcal meningitis in Delhi, India. Methods: Eight isolates of N. meningitidis were collected from cerebrospinal fluid during October 2008 to May 2011 from occasional cases of meningococcal meningitis. Seven isolates were from outbreaks of meningococcal meningitis in 2005-2006 in Delhi and its adjoining areas. These were subjected to molecular typing of fetA gene, an outer membrane protein gene. Results: All 15 N. meningitides isolates studied were serogroup A. This surface exposed porin is putatively under immune pressure. Hence as a part of molecular characterization, genotyping was carried out to find out the diversity in outer membrane protein (FetA gene among the circulating isolates of N. meningitidis. All 15 isolates proved to be of the same existing allele type of FetA variable region (VR when matched with global database. The allele found was F3-1 for all the isolates. Interpretation & conclusions: There was no diversity reported in the outer membrane protein FetA in the present study and hence this protein appeared to be a stable molecule. More studies on molecular characterization of FetA antigen are required from different serogroups circulating in different parts of the world.

A cross-sectional study assessing the pharyngeal carriage of Neisseria meningitidis in subjects aged 1-24 years in the city of Embu das Artes, São Paulo, Brazil.

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Weckx, Lily Yin; Puccini, Rosana Fiorini; Machado, Antónia; Gonçalves, Maria Gisele; Tuboi, Suely; de Barros, Eliana; Devadiga, Raghavendra; Ortega-Barria, Eduardo; Colindres, Romulo

Meningococcal carriage is a prerequisite for invasive infection. This cross-sectional study assessed the pharyngeal carriage prevalence in healthy subjects aged 1-24 years in Embu das Artes city, São Paulo, Brazil. Pharyngeal swabs were examined for the presence of Neisseria meningitidis. The isolates were tested for different serogroups using agglutination and polymerase chain reaction. A logistic regression model assessed any independent association between Neisseria meningitidis carriage and various risk factors. A total of 87/967 subjects (9%, 95% Confidence Interval (CI): 7.3-11.0) tested positive for N. meningitidis: 6.2% (95% CI: 3.8-9.4) in 1-4 years, 8.5% (95% CI: 5.1-13.0) in 5-9 years, 12.5% (95% CI: 7.8-18.6) in 10-14 years, 12.6% (95% CI: 7.4-19.7) in 15-19 years and 9% (95% CI: 4.9-14.9) in 20-24 years age groups. Highest carriage prevalence was observed in adolescents 10-19 years old. Serogroup C was predominant (18.4%) followed by serogroup B (12.6%). The 15-19 years age group showed a significant association between number of household members and carriers of N. meningitidis. This cross-sectional study is the first in Brazil to evaluate meningococcal carriage prevalence and associated factors in a wide age range. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Neisseria meningitidis RTX protein FrpC induced high levels of serum antibodies during invasive disease: polymorphism of frpC alleles and purification of recombinant FrpC

Czech Academy of Sciences Publication Activity Database

Osička, Radim; Kalmusová, J.; Křížová, P.; Šebo, Peter

2001-01-01

Roč. 69, č. 9 (2001), s. 5509-5519 ISSN 0019-9567 R&D Projects: GA ČR GV310/96/K102; GA MŠk ME 167 Institutional research plan: CEZ:AV0Z5020903 Keywords : Neisseria meningitidis * meningococcal infections Subject RIV: EE - Microbiology, Virology Impact factor: 4.212, year: 2001

Expression, purification and preliminary X-ray analysis of the Neisseria meningitidis outer membrane protein PorB

Energy Technology Data Exchange (ETDEWEB)

Tanabe, Mikio; Iverson, Tina M.; (Vanderbilt)

2010-01-28

The Neisseria meningitidis outer membrane protein PorB was expressed in Escherichia coli and purified from inclusion bodies by denaturation in urea followed by refolding in buffered LDAO on a size-exclusion column. PorB has been crystallized in three different crystal forms: C222, R32 and P6{sub 3}. The C222 crystal form may contain either one or two PorB monomers in the asymmetric unit, while both the R32 and P6{sub 3} crystal forms contained one PorB monomer in the asymmetric unit. Of the three, the P6{sub 3} crystal form had the best diffraction quality, yielding data extending to 2.3 {angstrom} resolution.

In vivo adaptation and persistence of Neisseria meningitidis within the nasopharyngeal mucosa.

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Kay O Johswich

Full Text Available Neisseria meningitidis (Nme asymptomatically colonizes the human nasopharynx, yet can initiate rapidly-progressing sepsis and meningitis in rare instances. Understanding the meningococcal lifestyle within the nasopharyngeal mucosa, a phase of infection that is prerequisite for disease, has been hampered by the lack of animal models. Herein, we compare mice expressing the four different human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs that can bind the neisserial Opa protein adhesins, and find that expression of human CEACAM1 is necessary and sufficient to establish intranasal colonization. During infection, in vivo selection for phase variants expressing CEACAM1-specific Opa proteins occurs, allowing mucosal attachment and entry into the subepithelial space. Consistent with an essential role for Opa proteins in this process, Opa-deficient meningococci were unable to colonize the CEACAM1-humanized mice. While simple Opa-mediated attachment triggered an innate response regardless of meningococcal viability within the inoculum, persistence of viable Opa-expressing bacteria within the CEACAM1-humanized mice was required for a protective memory response to be achieved. Parenteral immunization with a capsule-based conjugate vaccine led to the accumulation of protective levels of Nme-specific IgG within the nasal mucus, yet the sterilizing immunity afforded by natural colonization was instead conferred by Nme-specific IgA without detectable IgG. Considered together, this study establishes that the availability of CEACAM1 helps define the exquisite host specificity of this human-restricted pathogen, displays a striking example of in vivo selection for the expression of desirable Opa variants, and provides a novel model in which to consider meningococcal infection and immunity within the nasopharyngeal mucosa.

Structural alterations in a component of cytochrome c oxidase and molecular evolution of pathogenic Neisseria in humans.

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Marina Aspholm

2010-08-01

Full Text Available Three closely related bacterial species within the genus Neisseria are of importance to human disease and health. Neisseria meningitidis is a major cause of meningitis, while Neisseria gonorrhoeae is the agent of the sexually transmitted disease gonorrhea and Neisseria lactamica is a common, harmless commensal of children. Comparative genomics have yet to yield clear insights into which factors dictate the unique host-parasite relationships exhibited by each since, as a group, they display remarkable conservation at the levels of nucleotide sequence, gene content and synteny. Here, we discovered two rare alterations in the gene encoding the CcoP protein component of cytochrome cbb(3 oxidase that are phylogenetically informative. One is a single nucleotide polymorphism resulting in CcoP truncation that acts as a molecular signature for the species N. meningitidis. We go on to show that the ancestral ccoP gene arose by a unique gene duplication and fusion event and is specifically and completely distributed within species of the genus Neisseria. Surprisingly, we found that strains engineered to express either of the two CcoP forms conditionally differed in their capacity to support nitrite-dependent, microaerobic growth mediated by NirK, a nitrite reductase. Thus, we propose that changes in CcoP domain architecture and ensuing alterations in function are key traits in successive, adaptive radiations within these metapopulations. These findings provide a dramatic example of how rare changes in core metabolic proteins can be connected to significant macroevolutionary shifts. They also show how evolutionary change at the molecular level can be linked to metabolic innovation and its reversal as well as demonstrating how genotype can be used to infer alterations of the fitness landscape within a single host.

Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and modulates dendritic cell function.

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Steeghs, Liana; van Vliet, Sandra J; Uronen-Hansson, Heli; van Mourik, Andries; Engering, Anneke; Sanchez-Hernandez, Martha; Klein, Nigel; Callard, Robin; van Putten, Jos P M; van der Ley, Peter; van Kooyk, Yvette; van de Winkel, Jan G J

2006-02-01

Neisseria meningitidis lipopolysaccharide (LPS) has been identified as a major determinant of dendritic cell (DC) function. Here we report that one of a series of meningococcal mutants with defined truncations in the lacto-N-neotetraose outer core of the LPS exhibited unique strong adhesion and internalization properties towards DC. These properties were mediated by interaction of the GlcNAc(beta1-3)-Gal(beta1-4)-Glc-R oligosaccharide outer core of lgtB LPS with the dendritic-cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) lectin receptor. Activation of DC-SIGN with this novel oligosaccharide ligand skewed T-cell responses driven by DC towards T helper type 1 activity. Thus, the use of lgtB LPS may provide a powerful instrument to selectively induce the desired arm of the immune response and potentially increase vaccine efficacy.

Resistance to β-Lactams in Neisseria ssp Due to Chromosomally Encoded Penicillin-Binding Proteins.

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Zapun, André; Morlot, Cécile; Taha, Muhamed-Kheir

2016-09-28

Neisseria meningitidis and Neisseria gonorrhoeae are human pathogens that cause a variety of life-threatening systemic and local infections, such as meningitis or gonorrhoea. The treatment of such infection is becoming more difficult due to antibiotic resistance. The focus of this review is on the mechanism of reduced susceptibility to penicillin and other β-lactams due to the modification of chromosomally encoded penicillin-binding proteins (PBP), in particular PBP2 encoded by the penA gene. The variety of penA alleles and resulting variant PBP2 enzymes is described and the important amino acid substitutions are presented and discussed in a structural context.

How the Knowledge of Interactions between Meningococcus and the Human Immune System Has Been Used to Prepare Effective Neisseria meningitidis Vaccines

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R. Gasparini

2015-01-01

Full Text Available In the last decades, tremendous advancement in dissecting the mechanisms of pathogenicity of Neisseria meningitidis at a molecular level has been achieved, exploiting converging approaches of different disciplines, ranging from pathology to microbiology, immunology, and omics sciences (such as genomics and proteomics. Here, we review the molecular biology of the infectious agent and, in particular, its interactions with the immune system, focusing on both the innate and the adaptive responses. Meningococci exploit different mechanisms and complex machineries in order to subvert the immune system and to avoid being killed. Capsular polysaccharide and lipooligosaccharide glycan composition, in particular, play a major role in circumventing immune response. The understanding of these mechanisms has opened new horizons in the field of vaccinology. Nowadays different licensed meningococcal vaccines are available and used: conjugate meningococcal C vaccines, tetravalent conjugate vaccines, an affordable conjugate vaccine against the N. menigitidis serogroup A, and universal vaccines based on multiple antigens each one with a different and peculiar function against meningococcal group B strains.

Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan

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Chang Hsiu-Li

2006-02-01

Full Text Available Abstract Background Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001–2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern. Methods Neisseria meningitidis isolates from patients with meningococcal disease from 1996 to 2002 were collected and characterized by serogrouping, pulsed-field gel electrophoresis (PFGE and multilocus sequence typing (MLST. The genetic relatedness and clonal relationship between the isolates were analyzed by using the PFGE patterns and the allelic profiles of the sequence types (STs. Results Serogroups A, B, C, W135, Y, and non-serogroupable Neisseria meningitidis were, respectively, responsible for 2%, 50%, 2%, 35%, 9%, and 2% of 158 culture-confirmed cases of meningococcal disease in 1996–2002. Among 100 N. meningitidis isolates available for PFGE and MLST analyses, 51 different PFGE patterns and 30 STs were identified with discriminatory indices of 0.95 and 0.87, respectively. Of the 30 STs, 21 were newly identified and of which 19 were found in serogroup B isolates. A total of 40 PFGE patterns were identified in 52 serogroup B isolates with the patterns distributed over several distinct clusters. In contrast, the isolates within each of the serogroups A, C, W135, and Y shared high levels of PFGE pattern similarity. Analysis of the allelic profile of the

Parameter and state estimation in a Neisseria meningitidis model: A study case of Niger

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Bowong, S.; Mountaga, L.; Bah, A.; Tewa, J. J.; Kurths, J.

2016-12-01

Neisseria meningitidis (Nm) is a major cause of bacterial meningitidis outbreaks in Africa and the Middle East. The availability of yearly reported meningitis cases in the African meningitis belt offers the opportunity to analyze the transmission dynamics and the impact of control strategies. In this paper, we propose a method for the estimation of state variables that are not accessible to measurements and an unknown parameter in a Nm model. We suppose that the yearly number of Nm induced mortality and the total population are known inputs, which can be obtained from data, and the yearly number of new Nm cases is the model output. We also suppose that the Nm transmission rate is an unknown parameter. We first show how the recruitment rate into the population can be estimated using real data of the total population and Nm induced mortality. Then, we use an auxiliary system called observer whose solutions converge exponentially to those of the original model. This observer does not use the unknown infection transmission rate but only uses the known inputs and the model output. This allows us to estimate unmeasured state variables such as the number of carriers that play an important role in the transmission of the infection and the total number of infected individuals within a human community. Finally, we also provide a simple method to estimate the unknown Nm transmission rate. In order to validate the estimation results, numerical simulations are conducted using real data of Niger.

Shifts in the Antibiotic Susceptibility, Serogroups, and Clonal Complexes of Neisseria meningitidis in Shanghai, China: A Time Trend Analysis of the Pre-Quinolone and Quinolone Eras.

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Chen, Mingliang; Guo, Qinglan; Wang, Ye; Zou, Ying; Wang, Gangyi; Zhang, Xi; Xu, Xiaogang; Zhao, Miao; Hu, Fupin; Qu, Di; Chen, Min; Wang, Minggui

2015-06-01

Fluoroquinolones have been used broadly since the end of the 1980s and have been recommended for Neisseria meningitidis prophylaxis since 2005 in China. The aim of this study was to determine whether and how N. meningitidis antimicrobial susceptibility, serogroup prevalence, and clonal complex (CC) prevalence shifted in association with the introduction and expanding use of quinolones in Shanghai, a region with a traditionally high incidence of invasive disease due to N. meningitidis. A total of 374 N. meningitidis isolates collected by the Shanghai Municipal Center for Disease Control and Prevention between 1965 and 2013 were studied. Shifts in the serogroups and CCs were observed, from predominantly serogroup A CC5 (84%) in 1965-1973 to serogroup A CC1 (58%) in 1974-1985, then to serogroup C or B CC4821 (62%) in 2005-2013. The rates of ciprofloxacin nonsusceptibility in N. meningitidis disease isolates increased from 0% in 1965-1985 to 84% (31/37) in 2005-2013 (p convenience isolates from 1965-1985 were available. The increasing prevalence of ciprofloxacin resistance since 2005 in Shanghai was associated with the spread of hypervirulent lineages CC4821 and CC5. Two resistant meningococcal clones ChinaCC4821-R1-C/B and ChinaCC5-R14-A have emerged in Shanghai during the quinolone era. Ciprofloxacin should be utilized with caution for the chemoprophylaxis of N. meningitidis in China.

Encuesta de portadores de Neisseria meningitidis en el Área de Salud de Gran Canaria

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García Rojas Amós

2000-01-01

Full Text Available FUNDAMENTOS: Se plantea A Conocer la tasa de portadores y los tipos circulantes de Neisseria Meningitidis en la población residente en el área de salud de Gran Canaria. B Conocer el patrón de distribución de estos portadores. MÉTODOS: Se realizó un diseño descriptivo transversal, con un muestreo aleatorio en etapas múltiples y por conglomerados. Se determinó un tamaño muestral mínimo de 707 personas para una prevalencia esperada del 8,6 %, con una confianza del 95,6 % y precisión de 0,02. Asumiendo que un 15 % de las personas no quisieran colaborar, se incrementó el tamaño muestral a 831 personas, distribuidas en cada conglomerado de manera proporcional a la población existente. Este tamaño se distribuyó a su vez, en cuatro grandes grupos de edad y sexo, proporcionalmente a su importancia en cada zona básica de salud seleccionada aleatoriamente. Los individuos de la muestra se identificaban entre los que acudían a las unidades de extracción, y una vez superados los criterios de exclusión se les solicitaba su colaboración voluntaria en el estudio. Si aceptaban, se les cumplimentaba un cuestionario que englobaba diferentes variables de interés epidemiológico y se les realizaba un frotis faríngeo. Al haber seleccionado los equipos de Atención Primaria con muestreo aleatorio simple y seguir el mismo método para elegir los individuos dentro de ellos, la estimación de la prevalencia se realizó mediante estimador no sesgado. RESULTADOS: Se obtuvieron un total de 828 muestras, lo que supuso un 99,6% de las previstas. Salvo tres, todos los individuos seleccionados participaron voluntariamente en el estudio, lo que le confiere una alta representatividad. Todas las cepas obtenidas correspondían a N. Meningitidis Serogrupo B, salvo una identificada como N. Meningitidis Serogrupo C Sero/Subtipo 4:P1.2,5. Las cepas de N. Meningitidis serogrupo B identificadas, correspondían a 25 serosubtipos diferentes. La prevalencia puntual

[Surveillance of Neisseria meningitidis in Argentina, 1993-2005: distribution of serogroups, serotypes and serosubtypes isolated from invasive disease].

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Chiávetta, L; Chávez, E; Ruzic, A; Mollerach, M; Regueira, M

2007-01-01

Neisseria meningitidis is an important cause of meningitis, bacteremia and septic shock syndrome. We herein present the distribution of serogroups, serotypes and serosubtypes of 2244 isolates of N. meningitidis from patients with meningitis or meningococcemia, received within the period 1993-2005, in the National Reference Laboratory, INEI-ANLIS "Dr. Carlos G. Malbrán", from 33 Argentine hospitals that are included in a National Network devoted to for the study of bacterial meningitis. Between 1993-1995, serogroup B was prevalent (66%) whereas in the period from 1995-2001, serogroup C prevailed (65%). However, following but after that period, the prevalence of serogroup B was recovered. In the last 5 years of the studied period, the serogroups Y and W135 represented as a whole a 15.6% as a whole whereas up to the year 2000 during the first 6 years they accounted for it was of 4.7%. Higher diversity in the distribution of serotypes and serosubtypes was observed within serogroup B. The nonsubtypable isolates throughout the period of study represented the 52.8%, this high percentage demonstrates the limited capacity of the serotyping for the determination of meningococcal/meningococcus subtypes. of meningococco.

Nucleotide sequence composition and method for detection of neisseria gonorrhoeae

International Nuclear Information System (INIS)

Lo, A.; Yang, H.L.

1990-01-01

This patent describes a composition of matter that is specific for Neisseria gonorrhoeae. It comprises: at least one nucleotide sequence for which the ratio of the amount of the sequence which hybridizes to chromosomal DNA of Neisseria gonorrhoeae to the amount of the sequence which hybridizes to chromosomal DNA of Neisseria meningitidis is greater than about five. The ratio being obtained by a method described

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

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Laura Morelli

2014-10-01

Full Text Available A vaccine to prevent infections from the emerging Neisseria meningitidis X (MenX is becoming an urgent issue. Recently MenX capsular polysaccharide (CPS fragments conjugated to CRM197 as carrier protein have been confirmed at preclinical stage as promising candidates for vaccine development. However, more insights about the minimal epitope required for the immunological activity of MenX CPS are needed. We report herein the chemical conjugation of fully synthetic MenX CPS oligomers (monomer, dimer, and trimer to CRM197. Moreover, improvements in some crucial steps leading to the synthesis of MenX CPS fragments are described. Following immunization with the obtained neoglycoconjugates, the conjugated trimer was demonstrated as the minimal fragment possessing immunogenic activity, even though significantly lower than a pentadecamer obtained from the native polymer and conjugated to the same protein. This finding suggests that oligomers longer than three repeating units are possibly needed to mimic the activity of the native polysaccharide.

Mucosal immunization using proteoliposome and cochleate structures from Neisseria meningitidis serogroup B induce mucosal and systemic responses.

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Campo, Judith Del; Zayas, Caridad; Romeu, Belkis; Acevedo, Reinaldo; González, Elizabeth; Bracho, Gustavo; Cuello, Maribel; Cabrera, Osmir; Balboa, Julio; Lastre, Miriam

2009-12-01

Most pathogens either invade the body or establish infection in mucosal tissues and represent an enormous challenge for vaccine development by the absence of good mucosal adjuvants. A proteoliposome-derived adjuvant from Neisseria meningitidis serogroup B (AFPL1, Adjuvant Finlay Proteoliposome 1) and its derived cochleate form (Co, AFCo1) contain multiple pathogen-associated molecular patterns as immunopotentiators, and can also serve as delivery systems to elicit a Th1-type immune response. The present studies demonstrate the ability of AFPL1and AFCo1 to induce mucosal and systemic immune responses by different mucosal immunizations routes and significant adjuvant activity for antibody responses of both structures: a microparticle and a nanoparticle with a heterologous antigen. Therefore, we used female mice immunized by intragastric, intravaginal, intranasal or intramuscular routes with both structures alone or incorporated with ovalbumin (OVA). High levels of specific IgG antibody were detected in all sera and in vaginal washes, but specific IgA antibody in external secretions was only detected in mucosally immunized mice. Furthermore, antigen specific IgG1 and IgG2a isotypes were all induced. AFPL1 and AFCo1 are capable of inducing IFN-gamma responses, and chemokine secretions, like MIP-1alpha and MIP-1beta. However, AFCo1 is a better alternative to induce immune responses at mucosal level. Even when we use a heterologous antigen, the AFCo1 response was better than with AFPL1 in inducing mucosal and systemic immune responses. These results support the use of AFCo1 as a potent Th1 inducing adjuvant particularly suitable for mucosal immunization.

Nucleotide sequence composition and method for detection of neisseria gonorrhoeae

Energy Technology Data Exchange (ETDEWEB)

Lo, A.; Yang, H.L.

1990-02-13

This patent describes a composition of matter that is specific for {ital Neisseria gonorrhoeae}. It comprises: at least one nucleotide sequence for which the ratio of the amount of the sequence which hybridizes to chromosomal DNA of {ital Neisseria gonorrhoeae} to the amount of the sequence which hybridizes to chromosomal DNA of {ital Neisseria meningitidis} is greater than about five. The ratio being obtained by a method described.

Expansion of a urethritis-associated Neisseria meningitidis clade in the United States with concurrent acquisition of N. gonorrhoeae alleles.

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Retchless, Adam C; Kretz, Cécilia B; Chang, How-Yi; Bazan, Jose A; Abrams, A Jeanine; Norris Turner, Abigail; Jenkins, Laurel T; Trees, David L; Tzeng, Yih-Ling; Stephens, David S; MacNeil, Jessica R; Wang, Xin

2018-03-02

Increased reports of Neisseria meningitidis urethritis in multiple U.S. cities during 2015 have been attributed to the emergence of a novel clade of nongroupable N. meningitidis within the ST-11 clonal complex, the "U.S. NmNG urethritis clade". Genetic recombination with N. gonorrhoeae has been proposed to enable efficient sexual transmission by this clade. To understand the evolutionary origin and diversification of the U.S. NmNG urethritis clade, whole-genome phylogenetic analysis was performed to identify its members among the N. meningitidis strain collection from the Centers for Disease Control and Prevention, including 209 urogenital and rectal N. meningitidis isolates submitted by U.S. public health departments in eleven states starting in 2015. The earliest representatives of the U.S. NmNG urethritis clade were identified from cases of invasive disease that occurred in 2013. Among 209 urogenital and rectal isolates submitted from January 2015 to September 2016, the clade accounted for 189/198 male urogenital isolates, 3/4 female urogenital isolates, and 1/7 rectal isolates. In total, members of the clade were isolated in thirteen states between 2013 and 2016, which evolved from a common ancestor that likely existed during 2011. The ancestor contained N. gonorrhoeae-like alleles in three regions of its genome, two of which may facilitate nitrite-dependent anaerobic growth during colonization of urogenital sites. Additional gonococcal-like alleles were acquired as the clade diversified. Notably, one isolate contained a sequence associated with azithromycin resistance in N. gonorrhoeae, but no other gonococcal antimicrobial resistance determinants were detected. Interspecies genetic recombination contributed to the early evolution and subsequent diversification of the U.S. NmNG urethritis clade. Ongoing acquisition of N. gonorrhoeae alleles by the U.S. NmNG urethritis clade may facilitate the expansion of its ecological niche while also increasing the

Live Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis activate the inflammatory response trhough Toll-like receptors 2, 4, and 9 in species-specific patterns

DEFF Research Database (Denmark)

Mogensen, T.H.; Paludan, Søren Riis; Kilian, Mogens

2006-01-01

activation by live bacteria. Here, we demonstrate that live Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis, the three principal causes of bacterial meningitis, use distinct sets of TLRs to trigger the inflammatory response. Using human embryonic kidney 293 cell lines......, each overexpressing one type of TLR, we found that S. pneumoniae triggered activation of the transcription factor nuclear factor-kappaB and expression of interleukin-8, only in cells expressing TLR2 or -9. The same response was evoked by H. influenzae in cells expressing TLR2 or -4 and by N...... and confirmed the essential role of these TLRs and also identified differential functions of TLRs in activation of the inflammatory response. Collectively, we here demonstrate that S. pneumoniae, H. influenzae, and N. meningitidis each activate several TLRs in species-specific patterns and show that infection...

Antimicrobial drug susceptibility of Neisseria meningitidis strains isolated from carriers

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Dayamí García

2000-06-01

Full Text Available When it is necessary to determine the susceptibility of Neisseria meningitidis (Nm strains to antimicrobial drugs, it is important to consider that it should be analyzed in a double context. One of them related to the use of drugs in a specific medical treatment; and the other; to chemoprophylatic drugs, both with the same purpose: the accurate selection of the “in vivo” antimicrobial agent. This requires the study of the sensitivity and resistance of strains isolated in both carriers and patients. With the aim of further studying the behavior of the strains that currently circulate in Cuba, an antimicrobial drug susceptibility study was conducted in 90 strains isolated from carriers during the first half of 1998. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs to: penicillin, ampicillin, rifampin, sulfadiazine, chloramphenicol, ciprofloxacin, ceftriaxone, cefotaxime. The study of the three latter drugs was done for the first time in our country. The search for β- lactamase-producer strains was also performed. There was a predominance of penicillin sensitive strains (82,2% with an intermediate sensitivity to ampicillin (57,8%, while 70% of the strains were sensitive to sulfadiazine. Regarding the rest of the antimicrobial drugs, 100% of the strains were sensitive. The paper shows the MICs for each drug as well as the phenotypic characteristics of the strains with the penicillin and sulfadiazine sensitivity and resistance patterns. No β-lactamase-producer strains were found.

Aplicación de una biblioteca de anticuerpos lineales humanos frente al polisacárido capsular de Neisseria meningitidis serogrupo B

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Emigdio León-Toirac

2013-12-01

Full Text Available Neisseria meningitidis serogrupo B produce aún morbimortalidad significativa. Su polisacárido capsular muestra similitud estructural con proteínas humanas y pobre inmunogenicidad, obstaculizando así el desarrollo de vacunas y anticuerpos monoclonales (AcM y policlonales contra esta bacteria. Recientemente se han creado bibliotecas artificiales de anticuerpos humanos expresados en bacteriófagos que reconocen específicamente a moléculas diana existentes, con la ventaja sobre los AcM convencionales por su rápida obtención, sin utilización de animales de laboratorio, lo que emerge como alternativa atractiva para la producción de AcM contra antígenos peculiares o complejos. Se realizó un trabajo de investigación básica, utilizando una biblioteca de fagos filamentosos que expresan constitutivamente regiones variables de anticuerpos humanos, que se enfrentó al polisacárido capsular de N. meningitidis serogrupo B. Los resultados que se obtuvieron mediante ELISA policlonal sugieren la existencia de anticuerpos humanos expresados en fagos que lo reconocen.

Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

OpenAIRE

Bielecka, Magdalena K.; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E.; Christodoulides, Myron

2014-01-01

A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human protein...

Genomic Epidemiology of Hypervirulent Serogroup W, ST-11 Neisseria meningitidis.

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Mustapha, Mustapha M; Marsh, Jane W; Krauland, Mary G; Fernandez, Jorge O; de Lemos, Ana Paula S; Dunning Hotopp, Julie C; Wang, Xin; Mayer, Leonard W; Lawrence, Jeffrey G; Hiller, N Luisa; Harrison, Lee H

2015-10-01

Neisseria meningitidis is a leading bacterial cause of sepsis and meningitis globally with dynamic strain distribution over time. Beginning with an epidemic among Hajj pilgrims in 2000, serogroup W (W) sequence type (ST) 11 emerged as a leading cause of epidemic meningitis in the African 'meningitis belt' and endemic cases in South America, Europe, Middle East and China. Previous genotyping studies were unable to reliably discriminate sporadic W ST-11 strains in circulation since 1970 from the Hajj outbreak strain (Hajj clone). It is also unclear what proportion of more recent W ST-11 disease clusters are caused by direct descendants of the Hajj clone. Whole genome sequences of 270 meningococcal strains isolated from patients with invasive meningococcal disease globally from 1970 to 2013 were compared using whole genome phylogenetic and major antigen-encoding gene sequence analyses. We found that all W ST-11 strains were descendants of an ancestral strain that had undergone unique capsular switching events. The Hajj clone and its descendants were distinct from other W ST-11 strains in that they shared a common antigen gene profile and had undergone recombination involving virulence genes encoding factor H binding protein, nitric oxide reductase, and nitrite reductase. These data demonstrate that recent acquisition of a distinct antigen-encoding gene profile and variations in meningococcal virulence genes was associated with the emergence of the Hajj clone. Importantly, W ST-11 strains unrelated to the Hajj outbreak contribute a significant proportion of W ST-11 cases globally. This study helps illuminate genomic factors associated with meningococcal strain emergence and evolution.

Whole genome typing of the recently emerged Canadian serogroup W Neisseria meningitidis sequence type 11 clonal complex isolates associated with invasive meningococcal disease

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Raymond S.W. Tsang

2018-04-01

Full Text Available Objectives: This study was performed to analyze the Canadian invasive serogroup W Neisseria meningitidis (MenW sequence type 11 (ST-11 clonal complex (CC isolates by whole genome typing and to compare Canadian isolates with similar isolates from elsewhere. Methods: Whole genome typing of 30 MenW ST-11 CC, 20 meningococcal group C (MenC ST-11 CC, and 31 MenW ST-22 CC isolates was performed on the Bacterial Isolate Genome Sequence database platform. Canadian MenW ST-11 CC isolates were compared with the 2000 MenW Hajj outbreak strain, as well as with MenW ST-11 CC from other countries. Results: Whole genome typing showed that the Canadian MenW ST-11 CC isolates were distinct from the traditional MenW ST-22 CC; they were not capsule-switched contemporary MenC strains that incorporated MenW capsules. While some recent MenW disease cases in Canada were caused by MenW ST-11 CC isolates showing relatedness to the 2000 MenW Hajj strain, many were non-Hajj isolates similar to current MenW ST-11 isolates found globally. Geographical and temporal variations in genotypes and surface protein antigen genes were found among the MenW ST-11 CC isolates. Conclusions: The current MenW ST-11 isolates did not arise by capsule switching from contemporary MenC ST-11 isolates. Both the Hajj-related and non-Hajj MenW ST-11 CC strains were associated with invasive meningococcal disease in Canada. Keywords: Neisseria meningitidis, Invasive meningococcal disease, Whole genome typing

Distribution of the type III DNA methyltransferases modA, modB and modD among Neisseria meningitidis genotypes: implications for gene regulation and virulence.

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Tan, Aimee; Hill, Dorothea M C; Harrison, Odile B; Srikhanta, Yogitha N; Jennings, Michael P; Maiden, Martin C J; Seib, Kate L

2016-02-12

Neisseria meningitidis is a human-specific bacterium that varies in invasive potential. All meningococci are carried in the nasopharynx, and most genotypes are very infrequently associated with invasive meningococcal disease; however, those belonging to the 'hyperinvasive lineages' are more frequently associated with sepsis or meningitis. Genome content is highly conserved between carriage and disease isolates, and differential gene expression has been proposed as a major determinant of the hyperinvasive phenotype. Three phase variable DNA methyltransferases (ModA, ModB and ModD), which mediate epigenetic regulation of distinct phase variable regulons (phasevarions), have been identified in N. meningitidis. Each mod gene has distinct alleles, defined by their Mod DNA recognition domain, and these target and methylate different DNA sequences, thereby regulating distinct gene sets. Here 211 meningococcal carriage and >1,400 disease isolates were surveyed for the distribution of meningococcal mod alleles. While modA11-12 and modB1-2 were found in most isolates, rarer alleles (e.g., modA15, modB4, modD1-6) were specific to particular genotypes as defined by clonal complex. This suggests that phase variable Mod proteins may be associated with distinct phenotypes and hence invasive potential of N. meningitidis strains.

Carriage of Neisseria Species in Communities with Different Rates of Meningococcal Disease

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Nicole Le Saux

1992-01-01

Full Text Available A single clone, Neisseria meningitidis serogroup C (C:2a:P1.2, was isolated from seven patients during a cluster of cases of meningococcal disease in Ontario in 1989. To determine whether the clone was present in asymptomatic individuals in the same population, pharyngeal swabs were taken from 7% (644 of 9125 of residents who were vaccinated during the outbreak. Rates of isolation of Neisseria species were also compared to those in two other geographical areas which did not have an elevated incidence of meningococcal disease. The rate of carriage of N meningitidis in the asymptomatic individuals sampled was between 1.9% and 5.4%. The clone isolated from patients was not present among the carrier strains as determined by sero- and subtyping and electrophoretic analysis of metabolic enzymes. Age greater than six years was the only factor associated with colonization with N meningitidis.

Whole-Genome Characterization of Epidemic Neisseria meningitidis Serogroup C and Resurgence of Serogroup W, Niger, 2015

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Kretz, Cecilia B.; Retchless, Adam C.; Sidikou, Fati; Issaka, Bassira; Ousmane, Sani; Schwartz, Stephanie; Tate, Ashley H.; Pana, Assimawè; Njanpop-Lafourcade, Berthe-Marie; Nzeyimana, Innocent; Nse, Ricardo Obama; Deghmane, Ala-Eddine; Hong, Eva; Brynildsrud, Ola Brønstad; Novak, Ryan T.; Meyer, Sarah A.; Oukem-Boyer, Odile Ouwe Missi; Ronveaux, Olivier; Caugant, Dominique A.; Taha, Muhamed-Kheir

2016-01-01

In 2015, Niger reported the largest epidemic of Neisseria meningitidis serogroup C (NmC) meningitis in sub-Saharan Africa. The NmC epidemic coincided with serogroup W (NmW) cases during the epidemic season, resulting in a total of 9,367 meningococcal cases through June 2015. To clarify the phylogenetic association, genetic evolution, and antibiotic determinants of the meningococcal strains in Niger, we sequenced the genomes of 102 isolates from this epidemic, comprising 81 NmC and 21 NmW isolates. The genomes of 82 isolates were completed, and all 102 were included in the analysis. All NmC isolates had sequence type 10217, which caused the outbreaks in Nigeria during 2013–2014 and for which a clonal complex has not yet been defined. The NmC isolates from Niger were substantially different from other NmC isolates collected globally. All NmW isolates belonged to clonal complex 11 and were closely related to the isolates causing recent outbreaks in Africa. PMID:27649262

Metabolismo intermedio e patogenicità microbica: studio della regolazione e dell’espressione differenziale del gene gdhA, codificante la L-glutammato deidrogenasi NADP-specifica, in isolati clinici di Neisseria meningitidis

OpenAIRE

Colicchio, Roberta

2006-01-01

Neisseria meningitidis (meningococco) è un batterio a ristretto spettro d’ospite e presenta “stili di vita” alternativi: commensale-patogeno, intracellulare-extracellulare. Un fattore cruciale per tale comportamento risiede nella capacità di sintetizzare ed utilizzare nutrienti essenziali per la propria sopravvivenza nei diversi microambienti dell’ospite durante un naturale ciclo infettivo. Dati di letteratura indicano che gdhA, codificante la L-glutammato deidrogenasi NADP-specifica (NADP...

Susceptibility to invasive meningococcal disease: polymorphism of complement system genes and Neisseria meningitidis factor H binding protein.

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Declan T Bradley

Full Text Available Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH is associated with altered risk of invasive meningococcal disease (IMD. We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP affected the risk association.We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test.Rs12085435 A in C8B was associated with odds ratio (OR of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction. A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10⁻⁴. There was no bacterial load (CtrA cycle threshold difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025.The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become

Genome wide expression profiling reveals suppression of host defence responses during colonisation by Neisseria meningitides but not N. lactamica.

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Hazel En En Wong

Full Text Available Both Neisseria meningitidis and the closely related bacterium Neisseria lactamica colonise human nasopharyngeal mucosal surface, but only N. meningitidis invades the bloodstream to cause potentially life-threatening meningitis and septicaemia. We have hypothesised that the two neisserial species differentially modulate host respiratory epithelial cell gene expression reflecting their disease potential. Confluent monolayers of 16HBE14 human bronchial epithelial cells were exposed to live and/or dead N. meningitidis (including capsule and pili mutants and N. lactamica, and their transcriptomes were compared using whole genome microarrays. Changes in expression of selected genes were subsequently validated using Q-RT-PCR and ELISAs. Live N. meningitidis and N. lactamica induced genes involved in host energy production processes suggesting that both bacterial species utilise host resources. N. meningitidis infection was associated with down-regulation of host defence genes. N. lactamica, relative to N. meningitidis, initiates up-regulation of proinflammatory genes. Bacterial secreted proteins alone induced some of the changes observed. The results suggest N. meningitidis and N. lactamica differentially regulate host respiratory epithelial cell gene expression through colonisation and/or protein secretion, and that this may contribute to subsequent clinical outcomes associated with these bacteria.

Clinical evaluation of a loop-mediated isothermal amplification (LAMP) assay for rapid detection of Neisseria meningitidis in cerebrospinal fluid.

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Lee, DoKyung; Kim, Eun Jin; Kilgore, Paul E; Kim, Soon Ae; Takahashi, Hideyuki; Ohnishi, Makoto; Anh, Dang Duc; Dong, Bai Qing; Kim, Jung Soo; Tomono, Jun; Miyamoto, Shigehiko; Notomi, Tsugunori; Kim, Dong Wook; Seki, Mitsuko

2015-01-01

Neisseria meningitidis (Nm) is a leading causative agent of bacterial meningitis in humans. Traditionally, meningococcal meningitis has been diagnosed by bacterial culture. However, isolation of bacteria from patients' cerebrospinal fluid (CSF) is time consuming and sometimes yields negative results. Recently, polymerase chain reaction (PCR)-based diagnostic methods of detecting Nm have been considered the gold standard because of their superior sensitivity and specificity compared with culture. In this study, we developed a loop-mediated isothermal amplification (LAMP) method and evaluated its ability to detect Nm in cerebrospinal fluid (CSF). We developed a meningococcal LAMP assay (Nm LAMP) that targets the ctrA gene. The primer specificity was validated using 16 strains of N. meningitidis (serogroup A, B, C, D, 29-E, W-135, X, Y, and Z) and 19 non-N. meningitidis species. Within 60 min, the Nm LAMP detected down to ten copies per reaction with sensitivity 1000-fold more than that of conventional PCR. The LAMP assays were evaluated using a set of 1574 randomly selected CSF specimens from children with suspected meningitis collected between 1998 and 2002 in Vietnam, China, and Korea. The LAMP method was shown to be more sensitive than PCR methods for CSF samples (31 CSF samples were positive by LAMP vs. 25 by PCR). The detection rate of the LAMP method was substantially higher than that of the PCR method. In a comparative analysis of the PCR and LAMP assays, the clinical sensitivity, specificity, positive predictive value, and negative predictive value of the LAMP assay were 100%, 99.6%, 80.6%, and 100%, respectively. Compared to PCR, LAMP detected Nm with higher analytical and clinical sensitivity. This sensitive and specific LAMP method offers significant advantages for screening patients on a population basis and for diagnosis in clinical settings.

Clinical evaluation of a loop-mediated isothermal amplification (LAMP assay for rapid detection of Neisseria meningitidis in cerebrospinal fluid.

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DoKyung Lee

Full Text Available Neisseria meningitidis (Nm is a leading causative agent of bacterial meningitis in humans. Traditionally, meningococcal meningitis has been diagnosed by bacterial culture. However, isolation of bacteria from patients' cerebrospinal fluid (CSF is time consuming and sometimes yields negative results. Recently, polymerase chain reaction (PCR-based diagnostic methods of detecting Nm have been considered the gold standard because of their superior sensitivity and specificity compared with culture. In this study, we developed a loop-mediated isothermal amplification (LAMP method and evaluated its ability to detect Nm in cerebrospinal fluid (CSF.We developed a meningococcal LAMP assay (Nm LAMP that targets the ctrA gene. The primer specificity was validated using 16 strains of N. meningitidis (serogroup A, B, C, D, 29-E, W-135, X, Y, and Z and 19 non-N. meningitidis species. Within 60 min, the Nm LAMP detected down to ten copies per reaction with sensitivity 1000-fold more than that of conventional PCR. The LAMP assays were evaluated using a set of 1574 randomly selected CSF specimens from children with suspected meningitis collected between 1998 and 2002 in Vietnam, China, and Korea. The LAMP method was shown to be more sensitive than PCR methods for CSF samples (31 CSF samples were positive by LAMP vs. 25 by PCR. The detection rate of the LAMP method was substantially higher than that of the PCR method. In a comparative analysis of the PCR and LAMP assays, the clinical sensitivity, specificity, positive predictive value, and negative predictive value of the LAMP assay were 100%, 99.6%, 80.6%, and 100%, respectively.Compared to PCR, LAMP detected Nm with higher analytical and clinical sensitivity. This sensitive and specific LAMP method offers significant advantages for screening patients on a population basis and for diagnosis in clinical settings.

Potential Capsule Switching from Serogroup Y to B: The Characterization of Three such Neisseria meningitidis Isolates Causing Invasive Meningococcal Disease in Canada

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Raymond SW Tsang

2005-01-01

Full Text Available Three group B Neisseria meningitidis isolates, recovered from meningococcal disease cases in Canada and typed as B:2c:P1.5, were characterized. Multilocus sequence typing showed that all three isolates were related because of an identical sequence type (ST 573. Isolates typed as 2c:P1.5 are common in serogroup Y meningococci but rare in isolates from serogroups B or C. Although no serogroup Y isolates have been typed as ST-573, eight isolates showed five to six housekeeping gene alleles that were identical to that of ST-573. This suggested that the B:2c:P1.5 isolates may have originated from serogroup Y organisms, possibly by capsule switching.

Neisseria meningitidis antigen NMB0088: sequence variability, protein topology and vaccine potential.

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Sardiñas, Gretel; Yero, Daniel; Climent, Yanet; Caballero, Evelin; Cobas, Karem; Niebla, Olivia

2009-02-01

The significance of Neisseria meningitidis serogroup B membrane proteins as vaccine candidates is continually growing. Here, we studied different aspects of antigen NMB0088, a protein that is abundant in outer-membrane vesicle preparations and is thought to be a surface protein. The gene encoding protein NMB0088 was sequenced in a panel of 34 different meningococcal strains with clinical and epidemiological relevance. After this analysis, four variants of NMB0088 were identified; the variability was confined to three specific segments, designated VR1, VR2 and VR3. Secondary structure predictions, refined with alignment analysis and homology modelling using FadL of Escherichia coli, revealed that almost all the variable regions were located in extracellular loop domains. In addition, the NMB0088 antigen was expressed in E. coli and a procedure for obtaining purified recombinant NMB0088 is described. The humoral immune response elicited in BALB/c mice was measured by ELISA and Western blotting, while the functional activity of these antibodies was determined in a serum bactericidal assay and an animal protection model. After immunization in mice, the recombinant protein was capable of inducing a protective response when it was administered inserted into liposomes. According to our results, the recombinant NMB0088 protein may represent a novel antigen for a vaccine against meningococcal disease. However, results from the variability study should be considered for designing a cross-protective formulation in future studies.

Lipoprotein NMB0928 from Neisseria meningitidis serogroup B as a novel vaccine candidate.

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Delgado, Maité; Yero, Daniel; Niebla, Olivia; González, Sonia; Climent, Yanet; Pérez, Yusleydis; Cobas, Karem; Caballero, Evelín; García, Darien; Pajón, Rolando

2007-12-05

Polysaccharide-based vaccines for serogroup B Neisseria meningitidis have failed to induce protective immunity. As a result, efforts to develop vaccines for serogroup B meningococcal disease have mostly focused on outer membrane proteins (OMP). Vaccine candidates based on meningococcal OMP have emerged in the form of outer membrane vesicles (OMVs) or, more recently, purified recombinant proteins, as alternative strategies for serogroup B vaccine development. In our group, the protein composition of the Cuban OMVs-based vaccine VA-MENGOC-BC was elucidated using two-dimensional gel electrophoresis and mass spectrometry. The proteomic map of this product allowed the identification of new putative protective proteins not previously reported as components of an antimeningococcal vaccine. In the present study, we have determined the immunogenicity and protective capacity of NMB0928, one of those proteins present in the OMVs. The antigen was obtained as a recombinant protein in Escherichia coli, purified and used to immunize mice. The antiserum produced against the protein was capable to recognize the natural protein in different meningococcal strains by whole-cell ELISA and Western blotting. After immunization, recombinant NMB0928 induced bactericidal antibodies, and when the protein was administered inserted into liposomes, the elicited antibodies were protective in the infant rat model. These results suggest that NMB0928 is a novel antigen worth to be included in a broadly protective meningococcal vaccine.

21 CFR 866.2410 - Culture medium for pathogenic Neisseria spp.

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2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Culture medium for pathogenic Neisseria spp. 866.2410 Section 866.2410 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2410...

THE SECOND BLIND SPOT: SMALL RETINAL VESSEL VASCULOPATHY AFTER VACCINATION AGAINST NEISSERIA MENINGITIDIS AND YELLOW FEVER.

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Moysidis, Stavros N; Koulisis, Nicole; Patel, Vivek R; Kashani, Amir H; Rao, Narsing A; Humayun, Mark S; Rodger, Damien C

2017-01-01

To describe a case of small retinal vessel vasculopathy postvaccination. We report the case of a 41-year-old white man who presented with a "second blind spot," describing a nasal scotoma in the right eye that started 4 days after vaccinations against Neisseria meningitidis and the yellow fever virus, and after a 2-month period of high stress and decreased sleep. Clinical examination, Humphrey visual field testing, and multimodal imaging with fundus photographs, autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography and angiography were performed. Clinical examination revealed a well-circumscribed, triangular area of retinal graying of about 1-disk diameter in size, located at the border of the temporal macula. This corresponded to a deep scotoma similar in size to the physiologic blind spot on Humphrey visual field 24-2 testing. There was mild hypoautofluoresence of this lesion on autofluorescence, hypofluorescence on fluorescein angiography, and focal attenuation of a small artery just distal to the bifurcation of an artery supplying the involved area. Spectral domain optical coherence tomography through the lesion conveyed hyperreflectivity most prominent in the inner and outer plexiform layers, with extension of the hyperreflectivity into the ganglion cell and inner nuclear layers. Spectral domain optical coherence tomography angiography demonstrated arteriolar and capillary dropout, more pronounced in the superficial retinal layer compared to the deeper retinal layer. At 1-month follow-up, his scotoma improved with monitoring, with reduction from -32 dB to -7 dB on Humphrey visual field testing. There was clinical resolution of the area of graying and decreased hyperreflectivity on spectral domain optical coherence tomography, with atrophy of the inner retina. Spectral domain optical coherence tomography angiography showed progression of arteriolar and capillary dropout, more so in the superficial than in the deep capillary

Differential expression of hemoglobin receptor, HmbR, between carriage and invasive isolates of Neisseria meningitidis contributes to virulence: lessons from a clonal outbreak.

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Sevestre, Julien; Diene, Seydina M; Aouiti-Trabelsi, Myriam; Deghmane, Ala-Eddine; Tournier, Isabelle; François, Patrice; Caron, François; Taha, Muhamed-Kheir

2018-04-11

Carriage and invasion balance in the pathogenesis of Neisseria meningitidis was analyzed during a recent clonal outbreak of meningococcal B in Normandy, France, that offered the opportunity to compare six isolates undistinguable by conventional typing (B:P1.7,16:F3-3/ST-32) isolated from invasive disease or pharyngeal asymptomatic carriage. Data from animal model (transgenic mice rendered susceptible to N. meningitidis infection) showed an absence of virulence for two non-capsulated carriage isolates, an intermediate virulence for two capsulated carriage isolates and a marked virulence for two capsulated invasive isolates. This differential pathogenesis well correlated with whole genome sequencing analysis that clustered together both isolates of each group together, forming their own arm within the Norman cluster. Gene-by-gene analysis specified that genes involved in iron acquisition were among the elements differentially represented in cluster of invasive isolates compared to cluster of capsulated carriage isolates. The hemoglobin receptor encoding gene hmbR was in an ON-phase in the capsulated invasive isolates while carriage capsulated isolates were in an OFF-phase. An ON-phase variant of a capsulated carriage isolate showed enhanced virulence. These data underline the role of phase variation (ON/OFF) of HmbR in the balance between disease isolates/carriage isolates.

Standardization of Neisseria meningitidis Serogroup B Colorimetric Serum Bactericida Assay

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Rodríguez, Tamara; Lastre, Miriam; Cedré, Barbara; Campo, Judith del; Bracho, Gustavo; Zayas, Caridad; Taboada, Carlos; Díaz, Miriam; Sierra, Gustavo; Pérez, Oliver

2002-01-01

The correlate of protection for serogroup B meningococci is not currently known, but for serogroup C it is believed to be the serum bactericidal assay (SBA). The current SBAs are labor intensive and the variations in protocols among different laboratories make interpretation of results difficult. A colorimetric SBA (cSBA), based on the ability of Neisseria meningitidis serogroup B to consume glucose, leading to acid production, was standardized by using group B strain Cu385-83 as the target. The cSBA results were compared to those obtained for a traditional colony-counting microassay (mSBA). Glucose and bromocresol purple pH indicator were added to the medium in order to estimate growth of cSBA target cell survivors through color change. Different variants of the assay parameters were optimized: growth of target cells (Mueller Hinton agar plates), target cell number (100 CFU/per well), and human complement source used at a final concentration of 25%. After the optimization, three other group B strains (H44/76, 490/91, and 511/91) were used as targets for the cSBA. The selection of the assay parameters and the standardization of cSBA were done with 13 sera from vaccinated volunteers. The titers were determined as the higher serum dilution that totally inhibited the bacterial growth marked by the color invariability of the pH indicator. This was detected visually as well as spectrophotometrically and was closely related to a significant difference in the growth of target cell survivors determined using Student’s t test. Intralaboratory reproducibility was ±1 dilution. The correlation between bactericidal median titers and specific immunoglobulin G serum concentration by enzyme immunoassay was high (r = 0.910, P < 0.01). The bactericidal titers generated by the cSBA and the mSBA were nearly identical, and there was a high correlation between the two assays (r = 0.974, P < 0.01). The standardized cSBA allows easy, fast, and efficient evaluation of samples. PMID

The Design of New Adjuvants for Mucosal Immunity to Neisseria meningitidis B in Nasally Primed Neonatal Mice for Adult Immune Response

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Tatiane Ferreira

2012-01-01

Full Text Available The aim of this study was to determine the value of detoxified Shiga toxins Stx1 and Stx2 (toxoids of Escherichia coli as mucosal adjuvants in neonatal mice for immunogenicity against the outer membrane proteins (OMPs of Neisseria meningitidis B. Mucosal immunization has been shown to be effective for the induction of antigen-specific immune responses in both the systemic and mucosal compartments. Systemic antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, and IgA and mucosal IgM and IgA were measured by ELISA using an N. meningitidis as an antigen. In addition, IFN-γ and IL-6 production were measured after stimulated proliferation of immune cells. Intranasal administration elicited a higher anti-OMP IgA response in both saliva and vaginal fluids. Our results suggest that both Stx1 and Stx2 toxoids are effective mucosal adjuvants for the induction of Ag-specific IgG, IgM, and IgA antibodies. The toxoids significantly enhanced the IgG and IgM response against OMPs with a potency equivalent to CT, with the response being characterized by both IgG1 and IgG2a isotypes, and increased IFN-gamma production. Additionally, bactericidal activity was induced with IgG and IgM antibodies of high avidity. These results support the use of the new toxoids as potent inducing adjuvants that are particularly suitable for mucosal immunization.

Outer membrane biogenesis in Escherichia coli, Neisseria meningitidis, and Helicobacter pylori: paradigm deviations in H. pylori.

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Liechti, George; Goldberg, Joanna B

2012-01-01

The bacterial pathogen Helicobacter pylori is capable of colonizing the gastric mucosa of the human stomach using a variety of factors associated with or secreted from its outer membrane (OM). Lipopolysaccharide (LPS) and numerous OM proteins have been shown to be involved in adhesion and immune stimulation/evasion. Many of these factors are essential for colonization and/or pathogenesis in a variety of animal models. Despite this wide array of potential targets present on the bacterial surface, the ability of H. pylori to vary its OM profile limits the effectiveness of vaccines or therapeutics that target any single one of these components. However, it has become evident that the proteins comprising the complexes that transport the majority of these molecules to the OM are highly conserved and often essential. The field of membrane biogenesis has progressed remarkably in the last few years, and the possibility now exists for targeting the mechanisms by which β-barrel proteins, lipoproteins, and LPS are transported to the OM, resulting in loss of bacterial fitness and significant altering of membrane permeability. In this review, the OM transport machinery for LPS, lipoproteins, and outer membrane proteins (OMPs) are discussed. While the principal investigations of these transport mechanisms have been conducted in Escherichia coli and Neisseria meningitidis, here these systems will be presented in the genetic context of ε proteobacteria. Bioinformatic analysis reveals that minimalist genomes, such as that of Helicobacter pylori, offer insight into the smallest number of components required for these essential pathways to function. Interestingly, in the majority of ε proteobacteria, while the inner and OM associated apparatus of LPS, lipoprotein, and OMP transport pathways appear to all be intact, most of the components associated with the periplasmic compartment are either missing or are almost unrecognizable when compared to their E. coli counterparts. Eventual

Immunological evaluation in nonhuman primates of formulations based on the chimeric protein P64k-domain III of dengue 2 and two components of Neisseria meningitidis.

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Valdés, Iris; Hermida, Lisset; Martín, Jorge; Menéndez, Tamara; Gil, Lázaro; Lazo, Laura; Castro, Jorge; Niebla, Olivia; López, Carlos; Bernardo, Lídice; Sánchez, Jorge; Romero, Yaremis; Martínez, Rafael; Guzmán, María G; Guillén, Gerardo

2009-02-11

The main problem in the development of successful vaccines against dengue based on recombinant proteins is the necessity to use potent adjuvants to reach a proper functional immune response. Our group reported the expression, characterization and immunological evaluation of the recombinant protein PD5, which contains the domain III of the Envelope protein from dengue 2 virus fused to the carrier protein P64k. This construct completely protected monkeys against viral challenge when the Freund's adjuvant was employed. Therefore, to define suitable formulations for human use, the present work relies on the evaluation of PD5, produced with a high purity and under GMP conditions, when formulated either with outer membrane vesicles (OMV) or the serogroup A capsular polysaccharide (CPS-A) from Neisseria meningitidis, both adsorbed on aluminium hydroxide. The antibody response to the formulation containing the CPS-A was clearly superior to that of the formulation with OMV. The experiment of in vivo protection supported this evidence, since only the group immunized with PD5 and CPS-A was partially protected upon viral challenge. This is the first study in which the polysaccharide A of N. meningitidis is successfully employed as adjuvant for viral antigens.

Portadores de Neisseria meningitidis, caracterización de las cepas aisladas y respuesta inmune basal a VA-MENGOC-BC

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María J. Valdés

2008-08-01

Full Text Available Con el propósito de conocer la prevalencia de portadores de Neisseria meningitidis en un grupo de adolescentes, los marcadores epidemiológicos de las cepas aisladas, así como los factores de riesgo asociados con el estado de portador y la respuesta inmune basal a VA-MENGOC-BC , se realizó un estudio transversal descriptivo de portadores en 189 estudiantes de 12-19 años de un politécnico de Ciego de Ávila, siguiendo las Normas Bioéticas establecidas. A los estudiantes se les realizó un exudado faríngeo y una extracción de sangre para la obtención de suero, así como una encuesta relacionada con aspectos de la investigación. La identificación de N. meningitidis se hizo por el sistema API NH (bioMérieux. Los serosubtipos e inmunotipos se clasificaron por ELISA de células enteras con anticuerpos monoclonales y la respuesta inmune basal se detectó por el Ensayo Bactericida del Suero. Se determinó la susceptibilidad antimicrobiana de las cepas frente a la penicilina, cloranfenicol, rifampicina, sulfadiacina sódica, ceftriaxona y ciprofloxacina. La prevalencia de portadores de N. meningitidis fue del 17%. Predominaron las cepas no agrupables (84,7%, seguidas por los serogrupos B (12,5% y Z (3,1%, destacándose la ausencia del C. Prevaleció el fenotipo NA:NT:P1.NST:L3,7,9 (12,5%, las cepas resistentes a la sulfadiacina (78,2% y sensibles a penicilina (81,3%, aunque el 18,7% mostró sensibilidad intermedia a este fármaco. Al resto de los antimicrobianos todas fueron sensibles. Se constató una respuesta inmune de memoria a la vacuna antimeningocócica (VAMENGOC-BC®, 12 años después de su aplicación, con títulos bactericidas anti C y B de 25 y 42%, respectivamente, resultados que pudieran estar influenciados por la inmunización sistemática que se realiza en Cuba con esta vacuna desde 1991.

Neisseria meningitidis differentially controls host cell motility through PilC1 and PilC2 components of type IV Pili.

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Philippe C Morand

Full Text Available Neisseria meningitidis is a strictly human pathogen that has two facets since asymptomatic carriage can unpredictably turn into fulminant forms of infection. Meningococcal pathogenesis relies on the ability of the bacteria to break host epithelial or endothelial cellular barriers. Highly restrictive, yet poorly understood, mechanisms allow meningococcal adhesion to cells of only human origin. Adhesion of encapsulated and virulent meningococci to human cells relies on the expression of bacterial type four pili (T4P that trigger intense host cell signalling. Among the components of the meningococcal T4P, the concomitantly expressed PilC1 and PilC2 proteins regulate pili exposure at the bacterial surface, and until now, PilC1 was believed to be specifically responsible for T4P-mediated meningococcal adhesion to human cells. Contrary to previous reports, we show that, like PilC1, the meningococcal PilC2 component is capable of mediating adhesion to human ME180 epithelial cells, with cortical plaque formation and F-actin condensation. However, PilC1 and PilC2 promote different effects on infected cells. Cellular tracking analysis revealed that PilC1-expressing meningococci caused a severe reduction in the motility of infected cells, which was not the case when cells were infected with PilC2-expressing strains. The amount of both total and phosphorylated forms of EGFR was dramatically reduced in cells upon PilC1-mediated infection. In contrast, PilC2-mediated infection did not notably affect the EGFR pathway, and these specificities were shared among unrelated meningococcal strains. These results suggest that meningococci have evolved a highly discriminative tool for differential adhesion in specific microenvironments where different cell types are present. Moreover, the fine-tuning of cellular control through the combined action of two concomitantly expressed, but distinctly regulated, T4P-associated variants of the same molecule (i.e. PilC1 and Pil

Genetic structure of Neisseria meningitidis serogroup C epidemic strains in South Brazil Estrutura genética de cepas epidêmicas de Neisseria meningitidis sorogrupo C do Sul do Brasil

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Claudio Tavares Sacchi

1995-08-01

Full Text Available In the present study we report the results of an analysis, based on serotyping, multilocus enzyme electrophoresis (MEE, and ribotyping of N. meningitidis serogroup C strains isolated from patients with meningococcal disease (MD in Rio Grande do Sul (RS and Santa Catarina (SC States, Brazil, as the Center of Epidemiology Control of Ministry of Health detected an increasing of MD cases due to this serogroup in the last two years (1992-1993. We have demonstrated that the MD due to N.meningitidis serogroup C strains in RS and SC States occurring in the last 4 years were caused mainly by one clone of strains (ET 40, with isolates indistinguishable by serogroup, serotype, subtype and even by ribotyping. One small number of cases that were not due to an ET 40 strains, represent closely related clones that probably are new lineages generated from the ET 40 clone referred as ET 11A complex. We have also analyzed N.meningitidis serogroup C strains isolated in the greater São Paulo in 1976 as representative of the first post epidemic year in that region. The ribotyping method, as well as MEE, could provide useful information about the clonal characteristics of those isolates and also of strains isolated in south Brazil. The strains from 1976 have more similarity with the actual endemic than epidemic strains, by the ribotyping, sulfonamide sensitivity, and MEE results. In conclusion, serotyping with monoclonal antibodies (C:2b:P1.3, MEE (ET 11 and ET 11A complex, and ribotyping by using ClaI restriction enzyme (Rb2, were useful to characterize these epidemic strains of N.meningitidis related to the increased incidence of MD in different States of south Brazil. It is mostly probable that these N.meningitidis serogroup C strains have poor or no genetic corelation with 1971-1975 epidemic serogroup C strains. The genetic similarity of members of the ET 11 and ET 11A complex were confirmed by the ribotyping method by using three restriction endonucleases

Methods for identifying Neisseria meningitidis carriers: a multi-center study in the African meningitis belt.

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Nicole E Basta

Full Text Available Detection of meningococcal carriers is key to understanding the epidemiology of Neisseria meningitidis, yet no gold standard has been established. Here, we directly compare two methods for collecting pharyngeal swabs to identify meningococcal carriers.We conducted cross-sectional surveys of schoolchildren at multiple sites in Africa to compare swabbing the posterior pharynx behind the uvula (U to swabbing the posterior pharynx behind the uvula plus one tonsil (T. Swabs were cultured immediately and analyzed using molecular methods.One thousand and six paired swab samples collected from schoolchildren in four countries were analyzed. Prevalence of meningococcal carriage was 6.9% (95% CI: 5.4-8.6% based on the results from both swabs, but the observed prevalence was lower based on one swab type alone. Prevalence based on the T swab or the U swab alone was similar (5.2% (95% CI: 3.8-6.7% versus 4.9% (95% CI: 3.6-6.4% respectively (p=0.6. The concordance between the two methods was 96.3% and the kappa was 0.61 (95% CI: 0.50-0.73, indicating good agreement.These two commonly used methods for collecting pharyngeal swabs provide consistent estimates of the prevalence of carriage, but both methods misclassified carriers to some degree, leading to underestimates of the prevalence.

Shifts in the Antibiotic Susceptibility, Serogroups, and Clonal Complexes of Neisseria meningitidis in Shanghai, China: A Time Trend Analysis of the Pre-Quinolone and Quinolone Eras.

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Mingliang Chen

2015-06-01

Full Text Available Fluoroquinolones have been used broadly since the end of the 1980s and have been recommended for Neisseria meningitidis prophylaxis since 2005 in China. The aim of this study was to determine whether and how N. meningitidis antimicrobial susceptibility, serogroup prevalence, and clonal complex (CC prevalence shifted in association with the introduction and expanding use of quinolones in Shanghai, a region with a traditionally high incidence of invasive disease due to N. meningitidis.A total of 374 N. meningitidis isolates collected by the Shanghai Municipal Center for Disease Control and Prevention between 1965 and 2013 were studied. Shifts in the serogroups and CCs were observed, from predominantly serogroup A CC5 (84% in 1965-1973 to serogroup A CC1 (58% in 1974-1985, then to serogroup C or B CC4821 (62% in 2005-2013. The rates of ciprofloxacin nonsusceptibility in N. meningitidis disease isolates increased from 0% in 1965-1985 to 84% (31/37 in 2005-2013 (p < 0.001. Among the ciprofloxacin-nonsusceptible isolates, 87% (27/31 were assigned to either CC4821 (n = 20 or CC5 (n = 7. The two predominant ciprofloxacin-resistant clones were designated ChinaCC4821-R1-C/B and ChinaCC5-R14-A. The ChinaCC4821-R1-C/B clone acquired ciprofloxacin resistance by a point mutation, and was present in 52% (16/31 of the ciprofloxacin-nonsusceptible disease isolates. The ChinaCC5-R14-A clone acquired ciprofloxacin resistance by horizontal gene transfer, and was found in 23% (7/31 of the ciprofloxacin-nonsusceptible disease isolates. The ciprofloxacin nonsusceptibility rate was 47% (7/15 among isolates from asymptomatic carriers, and nonsusceptibility was associated with diverse multi-locus sequence typing profiles and pulsed-field gel electrophoresis patterns. As detected after 2005, ciprofloxacin-nonsusceptible strains were shared between some of the patients and their close contacts. A limitation of this study is that isolates from 1986-2004 were not available

Independent evolution of the core and accessory gene sets in the genus Neisseria: insights gained from the genome of Neisseria lactamica isolate 020-06

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White Brian

2010-11-01

Full Text Available Abstract Background The genus Neisseria contains two important yet very different pathogens, N. meningitidis and N. gonorrhoeae, in addition to non-pathogenic species, of which N. lactamica is the best characterized. Genomic comparisons of these three bacteria will provide insights into the mechanisms and evolution of pathogenesis in this group of organisms, which are applicable to understanding these processes more generally. Results Non-pathogenic N. lactamica exhibits very similar population structure and levels of diversity to the meningococcus, whilst gonococci are essentially recent descendents of a single clone. All three species share a common core gene set estimated to comprise around 1190 CDSs, corresponding to about 60% of the genome. However, some of the nucleotide sequence diversity within this core genome is particular to each group, indicating that cross-species recombination is rare in this shared core gene set. Other than the meningococcal cps region, which encodes the polysaccharide capsule, relatively few members of the large accessory gene pool are exclusive to one species group, and cross-species recombination within this accessory genome is frequent. Conclusion The three Neisseria species groups represent coherent biological and genetic groupings which appear to be maintained by low rates of inter-species horizontal genetic exchange within the core genome. There is extensive evidence for exchange among positively selected genes and the accessory genome and some evidence of hitch-hiking of housekeeping genes with other loci. It is not possible to define a 'pathogenome' for this group of organisms and the disease causing phenotypes are therefore likely to be complex, polygenic, and different among the various disease-associated phenotypes observed.

The BER necessities: the repair of DNA damage in human-adapted bacterial pathogens.

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van der Veen, Stijn; Tang, Christoph M

2015-02-01

During colonization and disease, bacterial pathogens must survive the onslaught of the host immune system. A key component of the innate immune response is the generation of reactive oxygen and nitrogen species by phagocytic cells, which target and disrupt pathogen molecules, particularly DNA, and the base excision repair (BER) pathway is the most important mechanism for the repair of such oxidative DNA damage. In this Review, we discuss how the human-specific pathogens Mycobacterium tuberculosis, Helicobacter pylori and Neisseria meningitidis have evolved specialized mechanisms of DNA repair, particularly their BER pathways, compared with model organisms such as Escherichia coli. This specialization in DNA repair is likely to reflect the distinct niches occupied by these important human pathogens in the host.

Immunochemical studies and genetic background of two Neisseria meningitidis isolates expressing unusual capsule polysaccharide antigens with specificities of both serogroup Y and W135.

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Tsang, Raymond S W; Tsai, Chao Ming; Henderson, Averil M; Tyler, Shaun; Law, Dennis K S; Zollinger, Wendell; Jamieson, Frances

2008-03-01

We described 2 unusual Neisseria meningitidis strains isolated from epidemiologically unrelated invasive meningococcal disease cases in Ontario, Canada. Both isolates have features typical of serogroup Y N. meningitidis: are of serotype 2c, are of the multi-locus sequence types typical of the serogroup Y strains in Canada, and are genotyped as serogroup Y based on a previously described PCR-ELISA method that detects the serogroup-Y-specific siaD gene. However, both strains were poly-agglutinable in both anti-Y and anti-W135 antisera. Further studies on 1 of these 2 isolates showed the presence of glucose and galactose as well as sialic acids in its purified capsular polysaccharide, suggesting the presence of both serogroup Y and serogroup W135 polysaccharides. Rabbit antisera produced to this strain contained antibodies to both purified serogroup Y and serogroup W135 capsular polysaccharides. Absorption experiments with either serogroup Y or serogroup W135 bacteria confirmed the presence of antibodies to these 2 different polysaccharides. DNA sequencing of the cps operon from both isolates revealed a siaD gene with 99.7% homology to the published siaD sequence from a serogroup Y strain but with 3 point mutations that all resulted in amino acid changes. How these strains may affect results of routine surveillance, PCR diagnosis, and immuno-protection by vaccination are discussed.

The Biology of Neisseria Adhesins

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Miao-Chiu Hung

2013-07-01

Full Text Available Members of the genus Neisseria include pathogens causing important human diseases such as meningitis, septicaemia, gonorrhoea and pelvic inflammatory disease syndrome. Neisseriae are found on the exposed epithelia of the upper respiratory tract and the urogenital tract. Colonisation of these exposed epithelia is dependent on a repertoire of diverse bacterial molecules, extending not only from the surface of the bacteria but also found within the outer membrane. During invasive disease, pathogenic Neisseriae also interact with immune effector cells, vascular endothelia and the meninges. Neisseria adhesion involves the interplay of these multiple surface factors and in this review we discuss the structure and function of these important molecules and the nature of the host cell receptors and mechanisms involved in their recognition. We also describe the current status for recently identified Neisseria adhesins. Understanding the biology of Neisseria adhesins has an impact not only on the development of new vaccines but also in revealing fundamental knowledge about human biology.

Genetic distribution of noncapsular meningococcal group B vaccine antigens in Neisseria lactamica.

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Lucidarme, Jay; Gilchrist, Stefanie; Newbold, Lynne S; Gray, Stephen J; Kaczmarski, Edward B; Richardson, Lynne; Bennett, Julia S; Maiden, Martin C J; Findlow, Jamie; Borrow, Ray

2013-09-01

The poor immunogenicity of the meningococcal serogroup B (MenB) capsule has led to the development of vaccines targeting subcapsular antigens, in particular the immunodominant and diverse outer membrane porin, PorA. These vaccines are largely strain specific; however, they offer limited protection against the diverse MenB-associated diseases observed in many industrialized nations. To broaden the scope of its protection, the multicomponent vaccine (4CMenB) incorporates a PorA-containing outer membrane vesicle (OMV) alongside relatively conserved recombinant protein components, including factor H-binding protein (fHbp), Neisseria adhesin A (NadA), and neisserial heparin-binding antigen (NHBA). The expression of PorA is unique to meningococci (Neisseria meningitidis); however, many subcapsular antigens are shared with nonpathogenic members of the genus Neisseria that also inhabit the nasopharynx. These organisms may elicit cross-protective immunity against meningococci and/or occupy a niche that might otherwise accommodate pathogens. The potential for 4CMenB responses to impact such species (and vice versa) was investigated by determining the genetic distribution of the primary 4CMenB antigens among diverse members of the common childhood commensal, Neisseria lactamica. All the isolates possessed nhba but were devoid of fhbp and nadA. The nhba alleles were mainly distinct from but closely related to those observed among a representative panel of invasive MenB isolates from the same broad geographic region. We made similar findings for the immunogenic typing antigen, FetA, which constitutes a major part of the 4CMenB OMV. Thus, 4CMenB vaccine responses may impact or be impacted by nasopharyngeal carriage of commensal neisseriae. This highlights an area for further research and surveillance should the vaccine be routinely implemented.

Dinámicas de las interacciones de Neisseria meningitidis con las barreras celulares y los efectores inmunes

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Natalie J. Griffiths

2009-08-01

Full Text Available Neisseria meningitidis outer membrane (OM adhesins, Opa and Opc are known to exert significant influence on bacterial adhesion and invasion properties. They are also likely to affect the dynamics of cellular barrier penetration as they target human receptors that are subject to upregulation under inflammatory conditions. As some of the targeted receptors are also expressed on immune cells, it is possible that the OM proteins, when presented on bacteria or in OM vesicle vaccines, have the additional capacity to modulate host immune responses. In our recent studies, in vitro model systems were used to further explore these possibilities. The studies illustrated that the major human receptors targeted by Opa and Opc, i.e. CEACAMs and integrins, when upregulated by inflammatory cytokines, encourage enhanced cellular adhesion, invasion and barrier traversal. Tissue infiltration by fully capsulate bacteria via Opa proteins was also observed for piliated Opa+ meningococci. Other studies indicate that Opc increases meningococcal resistance to serum-mediated killing by binding to the complement regulatory molecule vitronectin. In addition, although adverse immunomodulatory effects have been reported for Opa-expressing gonococci and meningococcal OMVs, our studies indicate that interactions with CD4+ T cell expressed CEACAM1 does not offer immunomodulatory properties to meningococci.

Purificación de lipopolisacárido de Neisseria meningitidis a partir de una fracción colateral del proceso de producción de VA-MENGOC-BC®

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Julio A. Balboa

2008-04-01

Full Text Available El trabajo tuvo como objetivo purificar lipopolisacáridos (LPS de Neisseria meningitidis a partir de una fracción colateral del proceso de producción de la vacuna antimeningocócica VA-MENGOC-BC®, el sobrenadante que se obtiene del paso de ultracentrifugación durante el proceso de extracción de las proteínas de membrana externa del meningococo. La purificación se realizó mediante precipitación con etanol al 80%, extracción de las proteínas con fenol al 90% entre 65-70 ºC y ultracentrifugación fraccionada a 105,000 g. Se obtuvieron tres lotes de LPS, en total 1,069 g, con un contenido de proteínas, ácidos nucleicos y ácido sálico respecto al LPS de 0,5%, 0,3% y 2,2% (m/m respectivamente. La evaluación por cromatografía mostró una alta integridad molecular, con valores de constante de distribución reproducibles (0,36-0,38 y una posible asociación del ácido siálico al LPS. Se apreció homogeneidad en el perfil electroforético de los tres lotes y alta actividad endotóxica. El LPS purificado fue identificado fundamentalmente como del inmunotipo L3,7,9. El procedimiento de purificación empleado permite aprovechar una fracción colateral del proceso de producción de la vacuna, es escalable, no incluye métodos cromatográficos, y posibilita la obtención de gran cantidad de LPS de Neisseria meningitidis, no disponible en el mercado, con elevada pureza y alta actividad endotóxica.

NeisseriaBase: a specialised Neisseria genomic resource and analysis platform.

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Zheng, Wenning; Mutha, Naresh V R; Heydari, Hamed; Dutta, Avirup; Siow, Cheuk Chuen; Jakubovics, Nicholas S; Wee, Wei Yee; Tan, Shi Yang; Ang, Mia Yang; Wong, Guat Jah; Choo, Siew Woh

2016-01-01

Background. The gram-negative Neisseria is associated with two of the most potent human epidemic diseases: meningococcal meningitis and gonorrhoea. In both cases, disease is caused by bacteria colonizing human mucosal membrane surfaces. Overall, the genus shows great diversity and genetic variation mainly due to its ability to acquire and incorporate genetic material from a diverse range of sources through horizontal gene transfer. Although a number of databases exist for the Neisseria genomes, they are mostly focused on the pathogenic species. In this present study we present the freely available NeisseriaBase, a database dedicated to the genus Neisseria encompassing the complete and draft genomes of 15 pathogenic and commensal Neisseria species. Methods. The genomic data were retrieved from National Center for Biotechnology Information (NCBI) and annotated using the RAST server which were then stored into the MySQL database. The protein-coding genes were further analyzed to obtain information such as calculation of GC content (%), predicted hydrophobicity and molecular weight (Da) using in-house Perl scripts. The web application was developed following the secure four-tier web application architecture: (1) client workstation, (2) web server, (3) application server, and (4) database server. The web interface was constructed using PHP, JavaScript, jQuery, AJAX and CSS, utilizing the model-view-controller (MVC) framework. The in-house developed bioinformatics tools implemented in NeisseraBase were developed using Python, Perl, BioPerl and R languages. Results. Currently, NeisseriaBase houses 603,500 Coding Sequences (CDSs), 16,071 RNAs and 13,119 tRNA genes from 227 Neisseria genomes. The database is equipped with interactive web interfaces. Incorporation of the JBrowse genome browser in the database enables fast and smooth browsing of Neisseria genomes. NeisseriaBase includes the standard BLAST program to facilitate homology searching, and for Virulence Factor

NeisseriaBase: a specialised Neisseria genomic resource and analysis platform

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Wenning Zheng

2016-03-01

Full Text Available Background. The gram-negative Neisseria is associated with two of the most potent human epidemic diseases: meningococcal meningitis and gonorrhoea. In both cases, disease is caused by bacteria colonizing human mucosal membrane surfaces. Overall, the genus shows great diversity and genetic variation mainly due to its ability to acquire and incorporate genetic material from a diverse range of sources through horizontal gene transfer. Although a number of databases exist for the Neisseria genomes, they are mostly focused on the pathogenic species. In this present study we present the freely available NeisseriaBase, a database dedicated to the genus Neisseria encompassing the complete and draft genomes of 15 pathogenic and commensal Neisseria species. Methods. The genomic data were retrieved from National Center for Biotechnology Information (NCBI and annotated using the RAST server which were then stored into the MySQL database. The protein-coding genes were further analyzed to obtain information such as calculation of GC content (%, predicted hydrophobicity and molecular weight (Da using in-house Perl scripts. The web application was developed following the secure four-tier web application architecture: (1 client workstation, (2 web server, (3 application server, and (4 database server. The web interface was constructed using PHP, JavaScript, jQuery, AJAX and CSS, utilizing the model-view-controller (MVC framework. The in-house developed bioinformatics tools implemented in NeisseraBase were developed using Python, Perl, BioPerl and R languages. Results. Currently, NeisseriaBase houses 603,500 Coding Sequences (CDSs, 16,071 RNAs and 13,119 tRNA genes from 227 Neisseria genomes. The database is equipped with interactive web interfaces. Incorporation of the JBrowse genome browser in the database enables fast and smooth browsing of Neisseria genomes. NeisseriaBase includes the standard BLAST program to facilitate homology searching, and for Virulence

Nitrogen consumption during batch cultivation of Neisseria meningitidis (serogroup C in Frantz medium Consumo de nitrogênio durante cultivo descontínuo de Neisseria meningitidis (sorogrupo C em meio de Frantz

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Júlia Baruque-Ramos

2001-12-01

Full Text Available Capsular polysaccharide, extracted from microorganism cultivations, is the principal antigen for elaboration of vaccine against the disease caused by Neisseria meningitidis serogroup C. The final protein content allowed in this vaccine is 1%. In order to find a relationship between nitrogen consumption and cell growth, including polysaccharide production, and cell nitrogen content, cultivations were carried out in an 80 liters bioreactor (total capacity, under the following conditions: Frantz medium; temperature of 35ºC; air flow of 5 L/min (0.125 vvm; agitation frequency of 120 rpm and vessel pressure of 6 psi (kLa = 0.07 min-1. Concentrations of biomass, total polysaccharide, cellular nitrogen, residual organic and inorganic nitrogen in the medium were measured during cultivation. From five cultivations carried out under the same conditions, a mean cell nitrogen percentage of 12.6% (w/w in respect to the dry biomass was found. The inorganic nitrogen in the medium did not change significantly along the cultivation time, whereas the organic nitrogen consumption was linearly related to cell growth, with constant yield factors (average of 8.44. Polysaccharide production kinetics followed the cell growth kinetics until the beginning of the stationary growth phase. A supplemental polysaccharide production was observed until the end of cultivation, but without cell nitrogen absorption. Thus, the results indicate that polysaccharide is produced in two phases, being the first one biomass formation followed by non-associated to growth.Polissacarídeo capsular, extraído de cultivos microbianos, é o principal antígeno para o preparo da vacina contra a doença causada por Neisseria meningitidis sorogrupo C. O conteúdo final de proteína permitido nessa vacina é de 1%. De modo a encontrar uma relação entre o consumo de nitrogênio, o crescimento microbiano (incluindo a produção de polissacarídeo e o conteúdo de nitrogênio celular, cultivos

Neisseria meningitidis elicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model.

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Borkowski, Julia; Li, Li; Steinmann, Ulrike; Quednau, Natascha; Stump-Guthier, Carolin; Weiss, Christel; Findeisen, Peter; Gretz, Norbert; Ishikawa, Hiroshi; Tenenbaum, Tobias; Schroten, Horst; Schwerk, Christian

2014-09-13

The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis worldwide. The blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus (CP), has been suggested as one of the potential entry sites of Nm into the CSF and can contribute to the inflammatory response during infectious diseases of the brain. Toll-like receptors (TLRs) are involved in mediating signal transduction caused by the pathogens. Using a recently established in vitro model of the human BCSFB based on human malignant CP papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain, MC58, employing transcriptome and RT-PCR analysis, cytokine bead array, and enzyme-linked immunosorbent assay (ELISA). In comparison, we analyzed the answer to the closely related unencapsulated carrier isolate Nm α14. The presence of TLRs in HIBCPP and their role during signal transduction caused by Nm was studied by RT-PCR and the use of specific agonists and mutant bacteria. We observed a stronger transcriptional response after infection with strain MC58, in particular with its capsule-deficient mutant MC58siaD-, which correlated with bacterial invasion levels. Expression evaluation and Gene Set Enrichment Analysis pointed to a NFκB-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IκBζ. Infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, including, among others, IL8, CXCL1-3, and the IκBζ target gene product IL6. The expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2/TLR6, rather than TLR4 or TLR2/TLR1, is involved in the cellular reaction following Nm infection. Our data show that Nm can initiate a pro-inflammatory response in human CP epithelial cells probably involving TLR2/TLR6

The structure of a contact-dependent growth-inhibition (CDI) immunity protein from Neisseria meningitidis MC58

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Tan, Kemin; Johnson, Parker M.; Stols, Lucy; Boubion, Bryan; Eschenfeldt, William; Babnigg, Gyorgy; Hayes, Christopher S.; Joachimiak, Andrezj; Goulding, Celia W.

2015-05-20

Contact-dependent growth inhibition (CDI) is an important mechanism of intercellular competition between neighboring Gram-negative bacteria. CDI systems encode large surface-exposed CdiA effector proteins that carry a variety of C-terminal toxin domains (CdiA-CTs). All CDI⁺bacteria also produce CdiI immunity proteins that specifically bind to the cognate CdiA-CT and neutralize its toxin activity to prevent auto-inhibition. Here, the X-ray crystal structure of a CdiI immunity protein fromNeisseria meningitidisMC58 is presented at 1.45 Å resolution. The CdiI protein has structural homology to the Whirly family of RNA-binding proteins, but appears to lack the characteristic nucleic acid-binding motif of this family. Sequence homology suggests that the cognate CdiA-CT is related to the eukaryotic EndoU family of RNA-processing enzymes. A homology model is presented of the CdiA-CT based on the structure of the XendoU nuclease fromXenopus laevis. Molecular-docking simulations predict that the CdiA-CT toxin active site is occluded upon binding to the CdiI immunity protein. Together, these observations suggest that the immunity protein neutralizes toxin activity by preventing access to RNA substrates.

Geotemporal analysis of Neisseria meningitidis clones in the United States: 2000-2005.

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Ann E Wiringa

Full Text Available The detection of meningococcal outbreaks relies on serogrouping and epidemiologic definitions. Advances in molecular epidemiology have improved the ability to distinguish unique Neisseria meningitidis strains, enabling the classification of isolates into clones. Around 98% of meningococcal cases in the United States are believed to be sporadic.Meningococcal isolates from 9 Active Bacterial Core surveillance sites throughout the United States from 2000 through 2005 were classified according to serogroup, multilocus sequence typing, and outer membrane protein (porA, porB, and fetA genotyping. Clones were defined as isolates that were indistinguishable according to this characterization. Case data were aggregated to the census tract level and all non-singleton clones were assessed for non-random spatial and temporal clustering using retrospective space-time analyses with a discrete Poisson probability model.Among 1,062 geocoded cases with available isolates, 438 unique clones were identified, 78 of which had ≥2 isolates. 702 cases were attributable to non-singleton clones, accounting for 66.0% of all geocoded cases. 32 statistically significant clusters comprised of 107 cases (10.1% of all geocoded cases were identified. Clusters had the following attributes: included 2 to 11 cases; 1 day to 33 months duration; radius of 0 to 61.7 km; and attack rate of 0.7 to 57.8 cases per 100,000 population. Serogroups represented among the clusters were: B (n = 12 clusters, 45 cases, C (n = 11 clusters, 27 cases, and Y (n = 9 clusters, 35 cases; 20 clusters (62.5% were caused by serogroups represented in meningococcal vaccines that are commercially available in the United States.Around 10% of meningococcal disease cases in the U.S. could be assigned to a geotemporal cluster. Molecular characterization of isolates, combined with geotemporal analysis, is a useful tool for understanding the spread of virulent meningococcal clones and patterns of

A comparison of the endotoxin biosynthesis and protein oxidation pathways in the biogenesis of the outer membrane of Escherichia coli and Neisseria meningitidis

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Susannah ePiek

2012-12-01

Full Text Available The Gram-negative bacterial cell envelope consists of an inner membrane (IM that surrounds the cytoplasm, and an asymmetrical outer-membrane (OM that forms a protective barrier to the external environment. The OM consists of lipopolysaccahride (LPS, phospholipids, outer membrane proteins (OMPs and lipoproteins. Oxidative protein folding mediated by periplasmic oxidoreductases is required for the correct biogenesis of the protein components, mainly constituents of virulence determinants such as pili, flagella and toxins, of the Gram-negative OM. Recently, periplasmic oxidoreductases have been implicated in LPS biogenesis of Escherichia coli and Neisseria meningitidis. Differences in OM biogenesis, in particular the transport pathways for endotoxin to the OM, the composition and role of the protein oxidation and isomerisation pathways and the regulatory networks that control them have been found in these two Gram-negative species suggesting that although form and function of the OM is conserved, these conserved pathways have been modified to suit the lifestyle of each organism.

Orientia, rickettsia, and leptospira pathogens as causes of CNS infections in Laos

DEFF Research Database (Denmark)

Dittrich, Sabine; Rattanavong, Sayaphet; Lee, Sue J

2015-01-01

BACKGROUND: Scrub typhus (caused by Orientia tsutsugamushi), murine typhus (caused by Rickettsia typhi), and leptospirosis are common causes of febrile illness in Asia; meningitis and meningoencephalitis are severe complications. However, scarce data exist for the burden of these pathogens......, Neisseria meningitidis, Haemophilus influenzae, S suis) and O tsutsugamushi, Rickettsia typhi/Rickettsia spp, and Leptospira spp infections in blood or cerebrospinal fluid (CSF). We analysed and compared causes and clinical and CSF characteristics between patient groups. FINDINGS: 1051 (95%) of 1112...... patients who presented had CSF available for analysis, of whom 254 (24%) had a CNS infection attributable to a bacterial or fungal pathogen. 90 (35%) of these 254 infections were caused by O tsutsugamushi, R typhi/Rickettsia spp, or Leptospira spp. These pathogens were significantly more frequent than...

Outbreak of serotype W135 Neisseria meningitidis in central river ...

African Journals Online (AJOL)

2012-06-21

Jun 21, 2012 ... program on immunization schedule of the Gambia and other countries within the meningitic epidemic belt. Key words: Neisseria ... The African meningitis belt extends from Ethiopia in the. East, to Senegal in the West within ..... surveillance and management system at the national level for effective control of ...

Functional analysis of the interdependence between DNA uptake sequence and its cognate ComP receptor during natural transformation in Neisseria species.

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Jamie-Lee Berry

Full Text Available Natural transformation is the widespread biological process by which "competent" bacteria take up free DNA, incorporate it into their genomes, and become genetically altered or "transformed". To curb often deleterious transformation by foreign DNA, several competent species preferentially take up their own DNA that contains specific DUS (DNA uptake sequence watermarks. Our recent finding that ComP is the long sought DUS receptor in Neisseria species paves the way for the functional analysis of the DUS-ComP interdependence which is reported here. By abolishing/modulating ComP levels in Neisseria meningitidis, we show that the enhancement of transformation seen in the presence of DUS is entirely dependent on ComP, which also controls transformation in the absence of DUS. While peripheral bases in the DUS were found to be less important, inner bases are essential since single base mutations led to dramatically impaired interaction with ComP and transformation. Strikingly, naturally occurring DUS variants in the genomes of human Neisseria commensals differing from DUS by only one or two bases were found to be similarly impaired for transformation of N. meningitidis. By showing that ComPsub from the N. subflava commensal specifically binds its cognate DUS variant and mediates DUS-enhanced transformation when expressed in a comP mutant of N. meningitidis, we confirm that a similar mechanism is used by all Neisseria species to promote transformation by their own, or closely related DNA. Together, these findings shed new light on the molecular events involved in the earliest step in natural transformation, and reveal an elegant mechanism for modulating horizontal gene transfer between competent species sharing the same niche.

Oral administration of recombinant Neisseria meningitidis PorA genetically fused to H. pylori HpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant.

Science.gov (United States)

Vasquez, Abel E; Manzo, Ricardo A; Soto, Daniel A; Barrientos, Magaly J; Maldonado, Aurora E; Mosqueira, Macarena; Avila, Anastasia; Touma, Jorge; Bruce, Elsa; Harris, Paul R; Venegas, Alejandro

2015-01-01

The Neisseria meningitidis outer membrane protein PorA from a Chilean strain was purified as a recombinant protein. PorA mixed with AbISCO induced bactericidal antibodies against N. meningitidis in mice. When PorA was fused to the Helicobacter pylori HpaA antigen gene, the specific response against H. pylori protein increased. Splenocytes from PorA-immunized mice were stimulated with PorA, and an increase in the secretion of IL-4 was observed compared with that of IFN-γ. Moreover, in an immunoglobulin sub-typing analysis, a substantially higher IgG1 level was found compared with IgG2a levels, suggesting a Th2-type immune response. This study revealed a peculiar behavior of the purified recombinant PorA protein per se in the absence of AbISCO as an adjuvant. Therefore, the resistance of PorA to proteolytic enzymes, such as those in the gastrointestinal tract, was analyzed, because this is an important feature for an oral protein adjuvant. Finally, we found that PorA fused to the H. pylori HpaA antigen, when expressed in Lactococcus lactis and administered orally, could enhance the antibody response against the HpaA antigen approximately 3 fold. These observations strongly suggest that PorA behaves as an effective oral adjuvant.

Could the multicomponent meningococcal serogroup B vaccine (4CMenB) control Neisseria meningitidis capsular group X outbreaks in Africa?

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Hong, Eva; Giuliani, Marzia Monica; Deghmane, Ala-Eddine; Comanducci, Maurizio; Brunelli, Brunella; Dull, Peter; Pizza, Mariagrazia; Taha, Muhamed-Kheir

2013-02-04

A new vaccine, 4CMenB, is composed of surface proteins of Neisseria meningitidis and is aimed to target serogroup B (MenB) isolates. The vaccine components are present in meningococcal isolates of other serogroups allowing potential use against meningococcal isolates belonging to non-B serogroups. Isolates of serogroup X (MenX) have been emerged in countries of the African meningitis belt. 4CMenB may offer a vaccine strategy against these isolates as there is no available capsule-based vaccine against MenX. We used the Meningococcal Antigen Typing System (MATS) to determine presence, diversity and levels of expression of 4CMenB antigens among 9 MenX isolates from several African countries in order to estimate the potential coverage of MenX by the 4CMenB vaccine. We performed bactericidal assays against these isolates, using pooled sera from 4CMenB-vaccinated infants, adolescents and adults. The African MenX isolates belonged to the same genotype but showed variation in the vaccine antigens. MATS data and bactericidal assays suggest coverage of the 9 African MenX isolates by 4CMenB but not of two unrelated MenX isolates from France. 4CMenB vaccine can be considered for further investigation to control MenX outbreaks in Africa. Copyright © 2012 Elsevier Ltd. All rights reserved.

Short-term and long-term antibody response by mice after immunization against Neisseria meningitidis B or diphtheria toxoid

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G.P. Silva

2013-02-01

Full Text Available Serogroup B Neisseria meningitidis (MenB is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization. Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine, its use should be restricted to outbreaks of meningococcal disease.

Meningococcal Disease Caused by Neisseria meningitidis Serogroup B Serotype 4 in São Paulo, Brazil, 1990 to 1996

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Sacchi Claudio Tavares

1998-01-01

Full Text Available A large epidemic of serogroup B meningococcal disease (MD, has been occurring in greater São Paulo, Brazil, since 1988.21 A Cuban-produced vaccine, based on outer-membrane-protein (OMP from serogroup B: serotype 4: serosubtype P1.15 (B:4:P1.15 Neisseria meningitidis, was given to about 2.4 million children aged from 3 months to 6 years during 1989 and 1990. The administration of vaccine had little or no measurable effects on this outbreak. In order to detect clonal changes that could explain the continued increase in the incidence of disease after the vaccination, we serotyped isolates recovered between 1990 and 1996 from 834 patients with systemic disease. Strains B:4:P1.15, which was detected in the area as early as 1977, has been the most prevalent phenotype since 1988. These strains are still prevalent in the area and were responsible for about 68% of 834 serogroup B cases in the last 7 years. We analyzed 438 (52% of these strains by restriction fragment length polymorphism (RFLPs of rRNA genes (ribotyping. The most frequent pattern obtained was referred to as Rb1 (68%. We concluded that the same clone of B:4:P1.15-Rb1 strains was the most prevalent strain and responsible for the continued increase of incidence of serogroup B MD cases in greater São Paulo during the last 7 years in spite of the vaccination trial.

Outbreak of Neisseria meningitidis C in workers at a large food-processing plant in Brazil: challenges of controlling disease spread to the larger community.

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Iser, B P M; Lima, H C A V; de Moraes, C; de Almeida, R P A; Watanabe, L T; Alves, S L A; Lemos, A P S; Gorla, M C O; Gonçalves, M G; Dos Santos, D A; Sobel, J

2012-05-01

SUMMARYAn outbreak of meningococcal disease (MD) with severe morbidity and mortality was investigated in midwestern Brazil in order to identify control measures. A MD case was defined as isolation of Neisseria meningitidis, or detection of polysaccharide antigen in a sterile site, or presence of clinical purpura fulminans, or an epidemiological link with a laboratory-confirmed case-patient, between June and August 2008. In 8 out of 16 MD cases studied, serogroup C ST103 complex was identified. Five (31%) cases had neurological findings and five (31%) died. The attack rate was 12 cases/100 000 town residents and 60 cases/100 000 employees in a large local food-processing plant. We conducted a matched case-control study of eight primary laboratory-confirmed cases (1:4). Factors associated with illness in single variable analysis were work at the processing plant [matched odds ratio (mOR) 22, 95% confidence interval (CI) 2·3-207·7, P10 000 plant employees) stopped propagation in the plant, but not in the larger community.

Co-ordinate action of bacterial adhesins and human carcinoembryonic antigen receptors in enhanced cellular invasion by capsulate serum resistant Neisseria meningitidis.

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Rowe, Helen A; Griffiths, Natalie J; Hill, Darryl J; Virji, Mumtaz

2007-01-01

Neisseria meningitidis (Nm) is a human specific opportunistic pathogen that occasionally penetrates mucosal barriers via the action of adhesins and invasins and evades host immune mechanisms during further dissemination via capsule expression. From in vitro studies, the primary adhesion of capsulate bacteria is believed to be mediated by polymeric pili, followed by invasion via outer membrane adhesins such as Opa proteins. As the latter requires the surface capsule to be down-modulated, invading bacteria would be serum sensitive and thus avirulent. However, there is recent evidence that capsulate bacteria may interact via Opa proteins when host cells express high levels of carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), their target receptors. Such a situation may arise following increased circulation of inflammatory cytokines that upregulate certain adhesion molecules on host cells. In this study, using a tetracycline controlled expression system, we have developed cell lines with inducible CEACAM expression to mimic post-inflammation state of target tissues and analysed the interplay between the three surface components capsule, pili and Opa proteins in cellular interactions. With two distinct cell lines, not only the level but also the rate of adhesion of capsulate Opa-expressing Nm increased concurrently with CEACAM density. Moreover, when threshold levels of receptor were reached, cellular invasion ensued in an Opa-dependent manner. In studies with cell lines intrinsically expressing pilus receptors, notable synergism in cellular interactions between pili and Opa of several meningococcal strains was observed and was independent of capsule type. A number of internalized bacteria were shown to express capsule and when directly isolated from host cells, these bacteria were as serum resistant as the inoculated phenotype. Furthermore, we observed that agents that block Opa-CEACAM binding substantially reduced cellular invasion, while maintaining

Optimization of Molecular Approaches to Genogroup Neisseria meningitidis Carriage Isolates and Implications for Monitoring the Impact of New Serogroup B Vaccines.

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Eduardo Rojas

Full Text Available The reservoir for Neisseria meningitidis (Nm is the human oropharynx. Implementation of Nm serogroup C (NmC glycoconjugate vaccines directly reduced NmC carriage. Prophylactic vaccines are now available to prevent disease caused by the five major Nm disease causing serogroups (ABCWY. Nm serogroup B (NmB vaccines are composed of antigens that are conserved across Nm serogroups and therefore have the potential to impact all Nm carriage. To assess the effect of these vaccines on carriage, standardized approaches to identify and group Nm are required. Real-time PCR (rt-PCR capsule grouping assays that were internally controlled to confirm Nm species were developed for eight serogroups associated with carriage (A, B, C, E, W, X, Y and Z. The grouping scheme was validated using diverse bacterial species associated with carriage and then used to evaluate a collection of diverse Nm carriage isolates (n=234. A scheme that also included porA and ctrA probes was able to speciate the isolates, while ctrA also provided insights on the integrity of the polysaccharide loci. Isolates were typed for the Nm vaccine antigen factor H binding protein (fHbp, and were found to represent the known diversity of this antigen. The porA rt-PCR yielded positive results with all 234 of the Nm carriage isolates. Genogrouping assays classified 76.5% (179/234 of these isolates to a group, categorized 53 as nongenogroupable (NGG and two as mixed results. Thirty seven NGG isolates evidenced a disrupted capsular polysaccharide operon judged by a ctrA negative result. Only 28.6% (67/234 of the isolates were serogrouped by slide agglutination (SASG, highlighting the reduced capability of carriage strains to express capsular polysaccharide. These rt-PCR assays provide a comprehensive means to identify and genogroup N. meningitidis in carriage studies used to guide vaccination strategies and to assess the impact of novel fHbp containing vaccines on meningococcal carriage.

Meningococcal outer membrane vesicle composition-dependent activation of the innate immune response

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Zariri, Afshin; Beskers, Joep; van de Waterbeemd, Bas; Hamstra, Hendrik Jan; Bindels, Tim H E; van Riet, Elly; van Putten, Jos P M; van der Ley, Peter

2016-01-01

Meningococcal outer membrane vesicles (OMVs) have been extensively investigated and successfully implemented as vaccines. They contain pathogen associated molecular patterns including lipopolysaccharide (LPS), capable of triggering innate immunity. However, Neisseria meningitidis contains an

Interactions of proteoliposomes from serogroup B Neisseria meningitidis with bone marrow-derived dendritic cells and macrophages: adjuvant effects and antigen delivery.

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Rodríguez, Tamara; Pérez, Oliver; Ménager, Nathalie; Ugrinovic, Sanja; Bracho, Gustavo; Mastroeni, Pietro

2005-01-26

Exposure to proteoliposomes from serogroup B Neisseria meningitidis (PL) induced up-regulation of MHC-II, MHC-I, CD40, CD80 and CD86 expression on the surface of murine bone marrow-derived dendritic cells (DC). CD40, CD80 and CD86 were up-regulated on bone marrow-derived macrophages (MPhi) upon stimulation with PL. Both DC and MPhi released TNFalpha, but only DC produced IL12(p70) in response to PL. A small increase in the expression of MHC-II, CD40 and CD86, as well as production of IL12(p70), was observed on the cell surface of DC, but not MPhi from LPS-non-responder C3H/HeJ after exposure to PL. DC, but not MPhi, incubated with PL containing ovalbumin (PL-OVA) presented OVA-specific peptides to CD4+ and CD8+ OVA-specific T-cell hybridomas. These data clearly indicate that PL exert an immunomodulatory effect on DC and MPhi, with some contribution of non-LPS components besides the main role of LPS. The work also shows the potential of PL as a general system to deliver antigens to DC for presentation to CD4+ and CD8+ T-cells.

Eficácia do moxalactam no tratamento de meningites purulentas causadas por Haemophilus infuenzae e Neisseria meningitidis Efficacy of moxalactam in the treatment of purulent meningitis caused by Haemophilus influenzae and Neisseria meningitidis

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Hagamenon R. da Silva

1984-03-01

Full Text Available Foi avaliada a eficácia do moxalactam no tratamento de meningites em crianças, causadas por H. influenzae (27 casos e N.meningitidis (6 casos. Dos 33 doentes tratados na dose de 100mg/Kg de peso (dose de ataque e 50mg de 12/12 horas por via venosa, 32 curaram-se. A tolerância ao produto foi muito boa, havendo alterações transitórias de transaminases e fosfatase alcalina; em um caso, houve hematoma posapendectomia, provavelmente relacionado ao uso deste antibiotico. Os níveis séricos e liquóricos do produto foram elevados; as concentrações no liquor excederam de muito a concentração bactericida mínima dos germes infectantes. O moxalactam se mostrou seguro e eficaz como terapia primária da meningite causada por H. influenzae e N.meningitidis em crianças.The clinical efficacy and safety of Moxalactam in purulent bacterial meningitis in children caused by H. influenzae (27 patients and N. meningitidis (6 patients was tested in a randon uncontrolled study. Clinical response was considered excelent, with cure of 32 of 33 patients. High levels of Moxalactam were achieved in the blood and cerebro-spinal fluid, with concentrations largely exceeding the minimum bacterial concentration (MIC for the infecting organisms. Tolerance was considered good, with only transient increases of transaminases and alkaline phosphatase in some patients; also, one patient developed a wound hematoma possibly related to Moxalactam therapy.

Clonal Distribution of Disease-Associated and Healthy Carrier Isolates of Neisseria meningitidis between 1983 and 2005 in Cuba ▿

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Climent, Yanet; Yero, Daniel; Martinez, Isabel; Martín, Alejandro; Jolley, Keith A.; Sotolongo, Franklin; Maiden, Martin C. J.; Urwin, Rachel; Pajón, Rolando

2010-01-01

In response to epidemic levels of serogroup B meningococcal disease in Cuba during the 1980s, the VA-MENGOC-BC vaccine was developed and introduced into the National Infant Immunization Program in 1991. Since then the incidence of meningococcal disease in Cuba has returned to the low levels recorded before the epidemic. A total of 420 Neisseria meningitidis strains collected between 1983 and 2005 in Cuba were analyzed by multilocus sequence typing (MLST). The set of strains comprised 167 isolated from disease cases and 253 obtained from healthy carriers. By MLST analysis, 63 sequence types (STs) were identified, and 32 of these were reported to be a new ST. The Cuban isolates were associated with 12 clonal complexes; and the most common were ST-32 (246 isolates), ST-53 (86 isolates), and ST-41/44 (36 isolates). This study also showed that the application of VA-MENGOC-BC, the Cuban serogroup B and C vaccine, reduced the frequency and diversity of hypervirulent clonal complexes ST-32 (vaccine serogroup B type-strain) and ST-41/44 and also affected other lineages. Lineages ST-8 and ST-11 were no longer found during the postvaccination period. The vaccine also affected the genetic composition of the carrier-associated meningococcal isolates. The number of carrier isolates belonging to hypervirulent lineages decreased significantly after vaccination, and ST-53, a sequence type common in carriers, became the predominant ST. PMID:20042619

Immunization and chemical conjugation of Bm95 obtained from Pichia pastoris enhances the immune response against vaccinal protein and Neisseria meningitidis capsular polysaccharide

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Rodriguez-Valle M

2014-03-01

Full Text Available Manuel Rodriguez-Valle,1 Leonardo Canan-Hadden,2 Olivia Niebla2 1Animal Biotechnology Division, 2Analytical Division, Centre for Genetic Engineering and Biotechnology, Havana, Cuba Abstract: The ectoparasite Rhipicephalus (Boophilus microplus causes severe economic losses to the cattle industry in tropical and subtropical regions, and transmits endoparasites, such as Babesia bovis. The glycoprotein Bm95 is homologous to Bm86, a surface membrane protein of gut epithelial cells in R. microplus, and has been shown to efficiently control this ectoparasite in regions of the Americas. The immunostimulant properties of Bm86 have already been demonstrated after its coinjection with hepatitis B surface antigen (HBsAg and the infectious bovine rhinotracheitis virus. This study evaluated the carrier and immunostimulant properties of Bm95 using low immunogenic Neisseria meningitidis capsular C polysaccharide (Men CpS and HBsAg. We produced two polysaccharide-Bm95 conjugates by carbodiimide (MenCpSBm-c and reductive amination (MenCpSBm-ra methods. These conjugates were characterized and evaluated in mice. Antibody titers against Men CpS were significantly higher in mice immunized with MenCpSBm-ra (2,350±250, P<0.01 than in those immunized with MenCpSBm-c (250±75 or Men CpS (570±104. The study data indicate effective immunological memory after booster inoculation in mice immunized with MenCpSBm-ra. Additionally, significant humoral immunity against HBsAg was documented in mice coimmunized via the intranasal route with recombinant Bm95 (11,400±345 and HBsAg (128,000±250 compared with mice immunized only with HBsAg (400±40 or Bm95 (5,461±150, P<0.01. In conclusion, the immunostimulatory properties of recombinant Bm95 make it a useful element for developing safer conjugated vaccines against bacterial pathogens and for evaluation against ticks and tick-borne diseases in the context of a polyvalent veterinary vaccine. Keywords: glycoconjugate, Bm86

Inhibition of the dapE-Encoded N-Succinyl-L,L-diaminopimelic Acid Desuccinylase from Neisseria meningitidis by L-Captopril.

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Starus, Anna; Nocek, Boguslaw; Bennett, Brian; Larrabee, James A; Shaw, Daniel L; Sae-Lee, Wisath; Russo, Marie T; Gillner, Danuta M; Makowska-Grzyska, Magdalena; Joachimiak, Andrzej; Holz, Richard C

2015-08-11

Binding of the competitive inhibitor L-captopril to the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Neisseria meningitidis (NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods. L-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE) with an IC50 of 3.3 μM and a measured Ki of 1.8 μM and displayed a dose-responsive antibiotic activity toward Escherichia coli. L-Captopril is also a competitive inhibitor of NmDapE with a Ki of 2.8 μM. To examine the nature of the interaction of L-captopril with the dinuclear active site of DapE, we have obtained electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) data for the enzymatically hyperactive Co(II)-substituted forms of both HiDapE and NmDapE. EPR and MCD data indicate that the two Co(II) ions in DapE are antiferromagnetically coupled, yielding an S = 0 ground state, and suggest a thiolate bridge between the two metal ions. Verification of a thiolate-bridged dinuclear complex was obtained by determining the three-dimensional X-ray crystal structure of NmDapE in complex with L-captopril at 1.8 Å resolution. Combination of these data provides new insights into binding of L-captopril to the active site of DapE enzymes as well as important inhibitor-active site residue interaction's. Such information is critical for the design of new, potent inhibitors of DapE enzymes.

Origin of the diversity in DNA recognition domains in phasevarion associated modA genes of pathogenic Neisseria and Haemophilus influenzae.

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Gawthorne, Jayde A; Beatson, Scott A; Srikhanta, Yogitha N; Fox, Kate L; Jennings, Michael P

2012-01-01

Phase variable restriction-modification (R-M) systems have been identified in a range of pathogenic bacteria. In some it has been demonstrated that the random switching of the mod (DNA methyltransferase) gene mediates the coordinated expression of multiple genes and constitutes a phasevarion (phase variable regulon). ModA of Neisseria and Haemophilus influenzae contain a highly variable, DNA recognition domain (DRD) that defines the target sequence that is modified by methylation and is used to define modA alleles. 18 distinct modA alleles have been identified in H. influenzae and the pathogenic Neisseria. To determine the origin of DRD variability, the 18 modA DRDs were used to search the available databases for similar sequences. Significant matches were identified between several modA alleles and mod gene from distinct bacterial species, indicating one source of the DRD variability was via horizontal gene transfer. Comparison of DRD sequences revealed significant mosaicism, indicating exchange between the Neisseria and H. influenzae modA alleles. Regions of high inter- and intra-allele similarity indicate that some modA alleles had undergone recombination more frequently than others, generating further diversity. Furthermore, the DRD from some modA alleles, such as modA12, have been transferred en bloc to replace the DRD from different modA alleles.

Improved OMV vaccine against Neisseria meningitidis using genetically engineered strains and a detergent-free purification process

NARCIS (Netherlands)

Waterbeemd, van de B.; Streefland, M.; Ley, de P.; Zomer, B.; Dijken, van H.; Martens, D.E.; Wijffels, R.H.; Pol, van der L.A.

2010-01-01

The use of detergent-extracted outer membrane vesicles (OMVs) is an established approach for development of a multivalent PorA vaccine against N. meningitidis serogroup B. Selective removal of lipopolysaccharide (LPS) decreases toxicity, but promotes aggregation and narrows the immune response.

Differences in the population structure of Neisseria meningitidis in two Australian states: Victoria and Western Australia.

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Shakeel Mowlaboccus

Full Text Available Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD. A recombinant vaccine called Bexsero® incorporates four subcapsular antigens (fHbp, NHBA, NadA and PorA which are used to assign a Bexsero® antigen sequence type (BAST to each meningococcal strain. The vaccine elicits an immune response against combinations of variants of these antigens which have been grouped into specific BAST profiles that have been shown to have different distributions within geographical locations thus potentially affecting the efficacy of the vaccine. In this study, invasive meningococcal disease isolates from the western seaboard of Australia (Western Australia; WA were compared to those from the south-eastern seaboard (Victoria; VIC from 2008 to 2012. Whole-genome sequencing (WGS of 131 meningococci from VIC and 70 meningococci from WA were analysed for MLST, FetA and BAST profiling. Serogroup B predominated in both jurisdictions and a total of 10 MLST clonal complexes (cc were shared by both states. Isolates belonging to cc22, cc103 and cc1157 were unique to VIC whilst isolates from cc60 and cc212 were unique to WA. Clonal complex 41/44 represented one-third of the meningococcal population in each state but the predominant ST was locally different: ST-6058 in VIC and ST-146 in WA. Of the 108 BAST profiles identified in this collection, only 9 BASTs were simultaneously observed in both states. A significantly larger proportion of isolates in VIC harboured alleles for the NHBA-2 peptide and fHbp-1, antigenic variants predicted to be covered by the Bexsero® vaccine. The estimate for vaccine coverage in WA (47.1% [95% CI: 41.1-53.1%] was significantly lower than that in VIC (66.4% [95% CI: 62.3-70.5%]. In conclusion, the antigenic structure of meningococci causing invasive disease in two geographically distinct states of Australia differed significantly during the study period which may affect vaccine effectiveness and highlights the

Identifying optimal vaccination strategies for serogroup A Neisseria meningitidis conjugate vaccine in the African meningitis belt.

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Sara Tartof

Full Text Available The optimal long-term vaccination strategies to provide population-level protection against serogroup A Neisseria meningitidis (MenA are unknown. We developed an age-structured mathematical model of MenA transmission, colonization, and disease in the African meningitis belt, and used this model to explore the impact of various vaccination strategies.The model stratifies the simulated population into groups based on age, infection status, and MenA antibody levels. We defined the model parameters (such as birth and death rates, age-specific incidence rates, and age-specific duration of protection using published data and maximum likelihood estimation. We assessed the validity of the model by comparing simulated incidence of invasive MenA and prevalence of MenA carriage to observed incidence and carriage data.The model fit well to observed age- and season-specific prevalence of carriage (mean pseudo-R2 0.84 and incidence of invasive disease (mean R2 0.89. The model is able to reproduce the observed dynamics of MenA epidemics in the African meningitis belt, including seasonal increases in incidence, with large epidemics occurring every eight to twelve years. Following a mass vaccination campaign of all persons 1-29 years of age, the most effective modeled vaccination strategy is to conduct mass vaccination campaigns every 5 years for children 1-5 years of age. Less frequent campaigns covering broader age groups would also be effective, although somewhat less so. Introducing conjugate MenA vaccine into the EPI vaccination schedule at 9 months of age results in higher predicted incidence than periodic mass campaigns.We have developed the first mathematical model of MenA in Africa to incorporate age structures and progressively waning protection over time. Our model accurately reproduces key features of MenA epidemiology in the African meningitis belt. This model can help policy makers consider vaccine program effectiveness when determining the

COMPARATIVE EVALUATION OF CULTURE MEDIA FOR PATHOGEN ISOLATION OF PURULENT BACTERIAL MENINGITIS

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Ya. V. Podkopaev

2016-01-01

Full Text Available The State Research Center for Applied Microbiology and Biotechnology has designed two nutrient media — chocolate agar and PBM-agar to isolate pathogens of purulent bacterial meningitis (PBM. In our previous research using collected microbial strains the media were shown to be highly susceptible and to provide the growth of Neisseria meningiti-dis, Streptococcus pneumoniae and Haemophilus influenzae strains, when inoculated with microbial suspensions containing single cells. When isolating Haemophilus influenzae, meningococci, and pneumococci the use of selective additives in both media assures selective isolation of required microorganisms, inhibiting contaminants. The objective of this research was to assess the media in bacteriological tests of clinical samples collected from the upper and lower respiratory tract in humans. The bacteriological plating of throat smear specimens (n = 90 from children and adults at the age of 0 to 66 with disorder of the upper respiratory tract on chocolate agar, PBM-agar and on a control medium in the absence of selective additives resulted in the equal amount of microbial cultures isolated. Of 154 isolated cultures 2, 23 and 9 were attributed to Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae, respectively. The plating of throat smears (n = 10 from healthy people at the age of 30 to 55 on the analyzable and control media in the presence of additives allowed us to selectively isolate Haemophilus influenzae and Streptococcus pneumoniae cultures without a quantitative loss, with contaminants inhibited. By their growth characteristics chocolate agar and PBM-agar were highly competitive with reference media being used in clinical practice for isolating main causative agents of purulent bacterial meningitis.

Genomic Investigation Reveals Highly Conserved, Mosaic, Recombination Events Associated with Capsular Switching among Invasive Neisseria meningitidis Serogroup W Sequence Type (ST)-11 Strains.

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Mustapha, Mustapha M; Marsh, Jane W; Krauland, Mary G; Fernandez, Jorge O; de Lemos, Ana Paula S; Dunning Hotopp, Julie C; Wang, Xin; Mayer, Leonard W; Lawrence, Jeffrey G; Hiller, N Luisa; Harrison, Lee H

2016-07-03

Neisseria meningitidis is an important cause of meningococcal disease globally. Sequence type (ST)-11 clonal complex (cc11) is a hypervirulent meningococcal lineage historically associated with serogroup C capsule and is believed to have acquired the W capsule through a C to W capsular switching event. We studied the sequence of capsule gene cluster (cps) and adjoining genomic regions of 524 invasive W cc11 strains isolated globally. We identified recombination breakpoints corresponding to two distinct recombination events within W cc11: A 8.4-kb recombinant region likely acquired from W cc22 including the sialic acid/glycosyl-transferase gene, csw resulted in a C→W change in capsular phenotype and a 13.7-kb recombinant segment likely acquired from Y cc23 lineage includes 4.5 kb of cps genes and 8.2 kb downstream of the cps cluster resulting in allelic changes in capsule translocation genes. A vast majority of W cc11 strains (497/524, 94.8%) retain both recombination events as evidenced by sharing identical or very closely related capsular allelic profiles. These data suggest that the W cc11 capsular switch involved two separate recombination events and that current global W cc11 meningococcal disease is caused by strains bearing this mosaic capsular switch. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Ion torrent personal genome machine sequencing for genomic typing of Neisseria meningitidis for rapid determination of multiple layers of typing information.

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Vogel, Ulrich; Szczepanowski, Rafael; Claus, Heike; Jünemann, Sebastian; Prior, Karola; Harmsen, Dag

2012-06-01

Neisseria meningitidis causes invasive meningococcal disease in infants, toddlers, and adolescents worldwide. DNA sequence-based typing, including multilocus sequence typing, analysis of genetic determinants of antibiotic resistance, and sequence typing of vaccine antigens, has become the standard for molecular epidemiology of the organism. However, PCR of multiple targets and consecutive Sanger sequencing provide logistic constraints to reference laboratories. Taking advantage of the recent development of benchtop next-generation sequencers (NGSs) and of BIGSdb, a database accommodating and analyzing genome sequence data, we therefore explored the feasibility and accuracy of Ion Torrent Personal Genome Machine (PGM) sequencing for genomic typing of meningococci. Three strains from a previous meningococcus serogroup B community outbreak were selected to compare conventional typing results with data generated by semiconductor chip-based sequencing. In addition, sequencing of the meningococcal type strain MC58 provided information about the general performance of the technology. The PGM technology generated sequence information for all target genes addressed. The results were 100% concordant with conventional typing results, with no further editing being necessary. In addition, the amount of typing information, i.e., nucleotides and target genes analyzed, could be substantially increased by the combined use of genome sequencing and BIGSdb compared to conventional methods. In the near future, affordable and fast benchtop NGS machines like the PGM might enable reference laboratories to switch to genomic typing on a routine basis. This will reduce workloads and rapidly provide information for laboratory surveillance, outbreak investigation, assessment of vaccine preventability, and antibiotic resistance gene monitoring.

Validación de un método de determinación del polisacárido B residual en vesículas de membrana externa de Neisseria meningitidis

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Jannete Rico

2010-08-01

Full Text Available La Cromatografía Líquida de Alta Resolución-Fluorescencia ha resultado ser una herramienta sensible para la detección de trazas en productos farmacéuticos y es utilizada frecuentemente para la cuantificación de algunos polisacáridos de origen bacteriano que poseen ácido siálico como unidad repetitiva. En este trabajo nos planteamos como objetivo establecer y validar el método de HPLC_Fluorescencia, para determinar el contenido de polisacárido B residual en vesículas de membrana externa de Neisseria meningitidis. Para ello se realizó el montaje del método HPLC-FL, utilizando una columna de fase reversa C18 (Ultrasphere ODS, Beckman, USA y se evaluaron seis lotes de vesículas de membrana externa de diferentes cepas Cu 385/83 y NZ 228. Se demostró que este método permitió la cuantificación de polisacárido B de una forma específica y exacta, y que cumplía con todos los parámetros de validación establecidos para un método de determinación de trazas mediante HPLC.

A dual role of extracellular DNA during biofilm formation of Neisseria meningitidis

DEFF Research Database (Denmark)

Lappann, M.; Claus, H.; van Alen, T.

2010-01-01

formation, whereas biofilm formation of cc with low point prevalence (ST-8 cc and ST-11 cc) was eDNA-independent. For initial biofilm formation, a ST-32 cc type strain, but not a ST-11 type strain, utilized eDNA. The release of eDNA was mediated by lytic transglycosylase and cytoplasmic N......-acetylmuramyl-l-alanine amidase genes. In late biofilms, outer membrane phospholipase A-dependent autolysis, which was observed in most cc, but not in ST-8 and ST-11 strains, was required for shear force resistance of microcolonies. Taken together, N. meningitidis evolved two different biofilm formation strategies, an e....... On the contrary, spreaders (ST-11 and ST-8 cc) are unable to use eDNA for biofilm formation and might compensate for poor colonization properties by high transmission rates....

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

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Jones Christopher

2005-01-01

Full Text Available Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development. This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.

Biased distribution of DNA uptake sequences towards genome maintenance genes

DEFF Research Database (Denmark)

Davidsen, T.; Rodland, E.A.; Lagesen, K.

2004-01-01

Repeated sequence signatures are characteristic features of all genomic DNA. We have made a rigorous search for repeat genomic sequences in the human pathogens Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae and found that by far the most frequent 9-10mers residing within...... in these organisms. Pasteurella multocida also displayed high frequencies of a putative DUS identical to that previously identified in H. influenzae and with a skewed distribution towards genome maintenance genes, indicating that this bacterium might be transformation competent under certain conditions....

Whole genome typing of the recently emerged Canadian serogroup W Neisseria meningitidis sequence type 11 clonal complex isolates associated with invasive meningococcal disease.

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Tsang, Raymond S W; Ahmad, Tauqeer; Tyler, Shaun; Lefebvre, Brigitte; Deeks, Shelley L; Gilca, Rodica; Hoang, Linda; Tyrrell, Gregory; Van Caeseele, Paul; Van Domselaar, Gary; Jamieson, Frances B

2018-04-01

This study was performed to analyze the Canadian invasive serogroup W Neisseria meningitidis (MenW) sequence type 11 (ST-11) clonal complex (CC) isolates by whole genome typing and to compare Canadian isolates with similar isolates from elsewhere. Whole genome typing of 30 MenW ST-11 CC, 20 meningococcal group C (MenC) ST-11 CC, and 31 MenW ST-22 CC isolates was performed on the Bacterial Isolate Genome Sequence database platform. Canadian MenW ST-11 CC isolates were compared with the 2000 MenW Hajj outbreak strain, as well as with MenW ST-11 CC from other countries. Whole genome typing showed that the Canadian MenW ST-11 CC isolates were distinct from the traditional MenW ST-22 CC; they were not capsule-switched contemporary MenC strains that incorporated MenW capsules. While some recent MenW disease cases in Canada were caused by MenW ST-11 CC isolates showing relatedness to the 2000 MenW Hajj strain, many were non-Hajj isolates similar to current MenW ST-11 isolates found globally. Geographical and temporal variations in genotypes and surface protein antigen genes were found among the MenW ST-11 CC isolates. The current MenW ST-11 isolates did not arise by capsule switching from contemporary MenC ST-11 isolates. Both the Hajj-related and non-Hajj MenW ST-11 CC strains were associated with invasive meningococcal disease in Canada. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival.

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Hebert Echenique-Rivera

2011-05-01

Full Text Available During infection Neisseria meningitidis (Nm encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ≈30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating

Evaluation of an Internally Controlled Multiplex Tth Endonuclease Cleavage Loop-Mediated Isothermal Amplification (TEC-LAMP Assay for the Detection of Bacterial Meningitis Pathogens

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Owen Higgins

2018-02-01

Full Text Available Bacterial meningitis infection is a leading global health concern for which rapid and accurate diagnosis is essential to reduce associated morbidity and mortality. Loop-mediated isothermal amplification (LAMP offers an effective low-cost diagnostic approach; however, multiplex LAMP is difficult to achieve, limiting its application. We have developed novel real-time multiplex LAMP technology, TEC-LAMP, using Tth endonuclease IV and a unique LAMP primer/probe. This study evaluates the analytical specificity, limit of detection (LOD and clinical application of an internally controlled multiplex TEC-LAMP assay for detection of leading bacterial meningitis pathogens: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae. Analytical specificities were established by testing 168 bacterial strains, and LODs were determined using Probit analysis. The TEC-LAMP assay was 100% specific, with LODs for S. pneumoniae, N. meningitidis and H. influenzae of 39.5, 17.3 and 25.9 genome copies per reaction, respectively. Clinical performance was evaluated by testing 65 archived PCR-positive samples. Compared to singleplex real-time PCR, the multiplex TEC-LAMP assay demonstrated diagnostic sensitivity and specificity of 92.3% and 100%, respectively. This is the first report of a single-tube internally controlled multiplex LAMP assay for bacterial meningitis pathogen detection, and the first report of Tth endonuclease IV incorporation into nucleic acid amplification diagnostic technology.

Evaluation of an Internally Controlled Multiplex Tth Endonuclease Cleavage Loop-Mediated Isothermal Amplification (TEC-LAMP) Assay for the Detection of Bacterial Meningitis Pathogens

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Clancy, Eoin; Cormican, Martin; Boo, Teck Wee; Cunney, Robert

2018-01-01

Bacterial meningitis infection is a leading global health concern for which rapid and accurate diagnosis is essential to reduce associated morbidity and mortality. Loop-mediated isothermal amplification (LAMP) offers an effective low-cost diagnostic approach; however, multiplex LAMP is difficult to achieve, limiting its application. We have developed novel real-time multiplex LAMP technology, TEC-LAMP, using Tth endonuclease IV and a unique LAMP primer/probe. This study evaluates the analytical specificity, limit of detection (LOD) and clinical application of an internally controlled multiplex TEC-LAMP assay for detection of leading bacterial meningitis pathogens: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae. Analytical specificities were established by testing 168 bacterial strains, and LODs were determined using Probit analysis. The TEC-LAMP assay was 100% specific, with LODs for S. pneumoniae, N. meningitidis and H. influenzae of 39.5, 17.3 and 25.9 genome copies per reaction, respectively. Clinical performance was evaluated by testing 65 archived PCR-positive samples. Compared to singleplex real-time PCR, the multiplex TEC-LAMP assay demonstrated diagnostic sensitivity and specificity of 92.3% and 100%, respectively. This is the first report of a single-tube internally controlled multiplex LAMP assay for bacterial meningitis pathogen detection, and the first report of Tth endonuclease IV incorporation into nucleic acid amplification diagnostic technology. PMID:29425124

Respuesta de anticuerpos inducidos por la vacuna antimeningocócica cubana VA-MENGOC-BC® frente a la cepa de Neisseria meningitidis B:4:P1.19,15 en adolescentes después de 12 años de inmunizados

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María A. Camaraza

2006-12-01

Full Text Available Se estudió la respuesta de anticuerpos inducida por la vacuna antimeningocócica cubana VA-MENGOC-BC® contra la cepa de Neisseria meningitidis B:4:P1.19,15 mediante el Ensayo Bactericida del Suero (EBS y ELISA de tipo indirecto, para medir anticuerpos contra vesículas de membrana externa (VME de N. meningitidis B a 184 adolescentes de un politécnico de Ciego de Ávila que fueron inmunizados en campañas masivas 12 años antes. Se realizaron extracciones de sangre antes de aplicar la primera dosis (T0, 4 semanas después de ésta (T1 y 4 semanas después de la segunda dosis (T2. Transcurridos 12 años de esta vacunación el 42% de los adolescentes presentó títulos bactericidas ≥ 1:4 frente a la cepa homóloga (B:4:P1.19,15 y el 98% mostró anticuerpos detectables contra las VME. En el EBS; el porcentaje de seroconversión T1/T0 fue del 57% y T2/T0 del 60%. Mediante ELISA la seroconversión fue del 59% y 54%, respectivamente, por lo que se demostró que la aplicación de una sola dosis después de 12 años indujo una respuesta inmune importante que puede sugerir una respuesta anamnésica.

Neisserial surface lipoproteins: structure, function and biogenesis.

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Hooda, Yogesh; Shin, Hyejin E; Bateman, Thomas J; Moraes, Trevor F

2017-03-01

The surface of many Gram-negative bacteria contains lipidated protein molecules referred to as surface lipoproteins or SLPs. SLPs play critical roles in host immune evasion, nutrient acquisition and regulation of the bacterial stress response. The focus of this review is on the SLPs present in Neisseria, a genus of bacteria that colonise the mucosal surfaces of animals. Neisseria contains two pathogens of medical interest, namely Neisseria meningitidis and N. gonorrhoeae. Several SLPs have been identified in Neisseria and their study has elucidated key strategies used by these pathogens to survive inside the human body. Herein, we focus on the identification, structure and function of SLPs that have been identified in Neisseria. We also survey the translocation pathways used by these SLPs to reach the cell surface. Specifically, we elaborate on the strategies used by neisserial SLPs to translocate across the outer membrane with an emphasis on Slam, a novel outer membrane protein that has been implicated in SLP biogenesis. Taken together, the study of SLPs in Neisseria illustrates the widespread roles played by this family of proteins in Gram-negative bacteria. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic transformation of Neisseria gonorrhoeae shows a strand preference

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Duffin, Paul M.; Seifert, H. Steven

2012-01-01

Natural transformation is the main means of horizontal genetic exchange in the obligate human pathogen Neisseria gonorrhoeae. Neisseria spp. have been shown to preferentially take up and transform their own DNA by recognizing a non-palindromic 10 or 12 nucleotide DNA uptake sequence (DUS10 or DUS12). We investigated the ability of the DUS12 to enhance single-stranded DNA (ssDNA) transformation. Given the non-palindromic nature of the DUS12, we tested whether both strands of the DUS equally en...

Three-dimensional structural analysis of the group B polysaccharide of Neisseria meningitidis 6275 by two-dimensional NMR: The polysaccharide is suggested to exist in helical conformations in solution

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Yamasaki, Ryohei; Bacon, B. (Univ. of California, San Francisco (USA) Veterans Administration Medical Center, San Francisco, CA (USA))

1991-01-22

The solution conformations of the group B polysaccharide of Neisseria meningitidis were analyzed by DQF-COSY and pure absorption 2D NOE NMR with three mixing times. The pyranose ring of the sialic acid residue was found to be in the {sup 2}C{sub 5} conformation. The DQF-COSY analysis indicated that the orientations of H6 and H7 and of H7 and H8 are both gauche. In order to overcome the difficulties in analyzing the NOE data due to the two sets of proton overlaps, molecular modeling of {alpha}-2,8-linked sialic acid oligomers was carried out to investigate possible conformers, and theoretical NOE calculations were performed by using CORMA (complete relaxation matrix analysis). The analysis suggests that the polysaccharide adopts helical structures for which the {phi} (defined by O6-C2-O8-C8) and {psi} (C2-O8-C8-C7) angles are in the following ranges: {phi}-60 to 0{degree}, {psi} 115-175{degree} or {phi} 90-120{degree}, {psi}55-175{degree}. The weak affinity of anti-B antibodies for smaller {alpha}-2,8-linked oligosaccharides may be due to the fact that such oligomers are more flexible and may not form an ordered structure as the poly(sialic acid) does.

Variabilidad de las meningoencefalitis bacterianas en el Hospital Pediátrico "Pepe Portilla" Variability of the bacterial meningoencephalitis at "Pepe Portilla" Paediatric Hospital

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Maydelin Fernández González

2009-03-01

Full Text Available Se realizó un estudio retrospectivo y prospectivo longitudinal de las Meningoencefalitis Bacterianas diagnosticadas en el Hospital Pediátrico "Pepe Portilla" en el año 2006 y 2007, con el objetivo de determinar los gérmenes que han aislado en dicha patología, comparándose con años anteriores desde 1992, analizando el impacto de la vacunación contra Neisseria meningitidis y Haemophilus influenzae. Los estudios de líquido cefalorraquídeo se realizaron como indican las normativas para estos casos. Se encontró que en el 2006 solo hubo un caso de meningitis a Neisseria meningitidis y en el 2007 dos casos de meningitis por Streptocuccus pneumoneae, y además que la incidencia de Neisseria meningitidis y Haemophilus influenzae disminuyó después de la aplicación de las vacunas VAMENGO BC y Hib de manera ostensible como lo hizo en el país en general, demostrándose la efectividad de dicha vacuna en nuestro medio.A retrospective-prospective and longitudinal study about Bacterial Meningoencephalitis diagnosed at "Pepe Portilla" Paediatric Hopital was carried out during 2006-2007 aimed at determining the isolated germs of this pathology comparing them with previous years (since 1992 and analyzing the impact of vaccination against Neisseria meningitidis y Haemophilus influenzae. The studies about cerebrospinal fluid were conducted as indicated by the rules towards these cases. Results showed that in 2006 only one case of meningitis a Neisseria meningitidis occurred and two cases of meningitis by Streptocuccus pneumoneae in 2007; besides the incidence of Neisseria meningitidis y Haemophilus influenza diminished after the vaccination with VAMENGON BC and Hib observed in all the country, showing the effectiveness of the vaccine in our environment.

Respuesta inmune mucosal inducida por proteoliposoma y cocleato derivados de N. meningitidis serogrupo B

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Judith del Campo

2009-08-01

Full Text Available Mucosal vaccination offers attractive advantages to conventional systemic vaccination. Most pathogens enter or establish infection at mucosal surfaces. This represents an enormous challenge for vaccine development. Nevertheless, the availability of safe and effective adjuvants that function mucosally is the major limitation. Therefore, we investigated the impact of mucosal immunization with the Neisseria meningitidis B proteoliposome (AFPL1, Adjuvant Finlay Proteoliposome 1 and its-derived cochleate (Co, AFCo1. They contain multiple PAMPs as immunopotentiators and have delivery system ability as well as Th1 polarization activity. Groups of female mice were immunized by nasal, oral, intravaginal, or intramuscular routes with three doses with AFPL1/AFCo1 alone or containing ovalbumin or glycoprotein (g D2 from Herpes Simplex Virus type 2 (HSV-2. High levels of specific IgG antibodies were detected in sera of mice vaccinated with either route. However, specific IgA antibodies were produced in saliva and vaginal wash only following mucosal delivering. The polarization to a Th1 pattern was confirmed by testing the induction of IgG2a/IgG2c antibody, positive delayed-type hypersensitivity reactions, and gIFN production. Additionally, AFCo1gD2 showed practically no vaginal HSV-2 replication and 100% protection against lethal vaginal HSV-2 challenge. In conclusion, the results support the use of AFCo1 as potent Th1 adjuvant for mucosal vaccines, particularly for nasal route.

[Meningococcal vulvovaginitis in a prepubertal girl].

Science.gov (United States)

Nathanson, M; Tisseron, B; de Pontual, L

2005-12-01

Neisseria meningitidis is an uncommon cause of vulvovaginitis in the prepubertal girl. The microorganism must not be mistaken for Neisseria gonorrhoeae, as the consequences of such an error may be serious. Colonization or infection by Neisseria meningitis is not uncommon in adolescents and adults. Vulvitis, even when it is recurrent, is not per se a good indicator of sexual abuse, but some microorganisms found by vaginal swab can make it possible, likely or certain. Sexual transmission of N. meningitidis has not been described in the prepubertal child.

Meningococcal B Vaccination (4CMenB in Infants and Toddlers

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Susanna Esposito

2015-01-01

Full Text Available Neisseria meningitidis is a Gram-negative pathogen that actively invades its human host and leads to the development of life-threatening pathologies. One of the leading causes of death in the world, N. meningitidis can be responsible for nearly 1,000 new infections per 100,000 subjects during an epidemic period. The bacterial species are classified into 12 serogroups, five of which (A, B, C, W, and Y cause the majority of meningitides. The three purified protein conjugate vaccines currently available target serogroups A, C, W, and Y. Serogroup B has long been a challenge but the discovery of the complete genome sequence of an MenB strain has allowed the development of a specific four-component vaccine (4CMenB. This review describes the pathogenetic role of N. meningitidis and the recent literature concerning the new meningococcal vaccine.

The use of high-throughput DNA sequencing in the investigation of antigenic variation: application to Neisseria species.

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John K Davies

Full Text Available Antigenic variation occurs in a broad range of species. This process resembles gene conversion in that variant DNA is unidirectionally transferred from partial gene copies (or silent loci into an expression locus. Previous studies of antigenic variation have involved the amplification and sequencing of individual genes from hundreds of colonies. Using the pilE gene from Neisseria gonorrhoeae we have demonstrated that it is possible to use PCR amplification, followed by high-throughput DNA sequencing and a novel assembly process, to detect individual antigenic variation events. The ability to detect these events was much greater than has previously been possible. In N. gonorrhoeae most silent loci contain multiple partial gene copies. Here we show that there is a bias towards using the copy at the 3' end of the silent loci (copy 1 as the donor sequence. The pilE gene of N. gonorrhoeae and some strains of Neisseria meningitidis encode class I pilin, but strains of N. meningitidis from clonal complexes 8 and 11 encode a class II pilin. We have confirmed that the class II pili of meningococcal strain FAM18 (clonal complex 11 are non-variable, and this is also true for the class II pili of strain NMB from clonal complex 8. In addition when a gene encoding class I pilin was moved into the meningococcal strain NMB background there was no evidence of antigenic variation. Finally we investigated several members of the opa gene family of N. gonorrhoeae, where it has been suggested that limited variation occurs. Variation was detected in the opaK gene that is located close to pilE, but not at the opaJ gene located elsewhere on the genome. The approach described here promises to dramatically improve studies of the extent and nature of antigenic variation systems in a variety of species.

Caracterización fenotípica de cepas invasivas de Neisseria meningitidis aisladas en Cuba durante 20 años

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Isabel Martínez

2006-04-01

Full Text Available Se investigaron los marcadores epidemiológicos (serogrupos, serotipos, subtipos, inmunotipos de 429 cepas invasivas, aisladas en Cuba durante 20 años (1982-2002. Basándonos en el comportamiento de la incidencia de la Enfermedad Meningocócica (EM en el período investigado, las cepas se distribuyeron en dos etapas: epidémica y postepidémica. La epidémica, comprendió 279 cepas aisladas entre 1982-1992 y la ostepidémica, incluyó 150 aislamientos pertenecientes al período comprendido entre 1993-2002. Todas se cultivaron en Agar Mueller Hinton con suero fetal bovino (5% y se incubaron 24-48 horas, 37 0C, en atmósfera húmeda con 5% de C02. La identificación de género, especie y serogrupo, se realizó mediante métodos convencionales; para la caracterización de los sero/subtipos e inmunotipos, se utilizó el ensayo inmunoenzimático (ELISA de células enteras con anticuerpos monoclonales. En ambas etapas predominó el serogrupo B (97,90%: epidémica (96,77% y postepidémica (100%. Sin embargo, el serogrupo C (1,43% y cepas no agrupables (1,8%, sólo se observaron en aislamientos de la etapa epidémica. Los otros marcadores prevalentes fueron: serotipo 4 (86,48%, subtipo P1.19,15 (78,32%, inmunotipo L3,7,9 (90,2% , todos mostraron cifras similares en ambos períodos.Predominó el fenotipo B:4:P1.19,15:L3,7,9 (69,69%, aunque, en la etapa postepidémica (77,34%, el porcentaje fue superior al de la etapa epidémica (65,66% (p<0,05; además, en las cepas de este período, se observó una mayor diversidad de asociaciones fenotípicas. Los resultados obtenidos de esta caracterización fenotípica de las cepas de Neisseria meningitidis aisladas de enfermos aporta datos valiosos al estudio, prevención y control exitoso de la EM en Cuba.

Multilocus Sequence Typing

OpenAIRE

Belén, Ana; Pavón, Ibarz; Maiden, Martin C.J.

2009-01-01

Multilocus sequence typing (MLST) was first proposed in 1998 as a typing approach that enables the unambiguous characterization of bacterial isolates in a standardized, reproducible, and portable manner using the human pathogen Neisseria meningitidis as the exemplar organism. Since then, the approach has been applied to a large and growing number of organisms by public health laboratories and research institutions. MLST data, shared by investigators over the world via the Internet, have been ...

El ácido siálico N-acetilado es inmunogénico e induce anticuerpos protectores contra Neisseria meningitidis

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Gregory R. Moe

2009-08-01

Full Text Available Recently, we showed that monoclonal antibodies (mAbs that are reactive with derivatives of polysialic acid containing de-N-acetylated neuraminic acid (Neu residues are protective against N. meningitidis group B strains (Moe et al. 2005, Infect Immun 73:2123; Flitter et al., in preparation. In addition, we found that fully de-N-acetylated PSA (i.e. poly alpha 2,8 Neu conjugated to tetanus toxoid (DeNAc elicits IgM and IgG antibodies of all subclasses in mice that bind to group B strains, activate human complement deposition, are protective in an infant rat model of meningococcal bacteremia and are bactericidal against group C strains (Moe et al, in press. We show here that anti-DeNAc mAbs, DA1 and DA2 (both IgM, are reactive with polysaccharides containing Neu, bind to group B, C, W135 and Y but not X strains grown in chemically defined media (CDM. However, when the group X strain is grown in CDM supplemented with human plasma, DA2 binds. Also both mAbs mediate bactericidal activity against B, C, W135, and X strains with human complement. The esults suggests that N. meningitidis express and/or acquire zwitterionic de-N-acetyl sialic acid antigens that can be the target of protective antibodies.

Interaction of Microbiology and Pathology in Women Undergoing Investigations for Infertility

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Joseph Debattista

2004-01-01

asymptomatic women undergoing investigation of infertility were correlated with the outcomes of microbiological screening for Chlamydia trachomatis, Mycoplasma pneumoniae, Mycoplasma hominis, ureaplasma species, Neisseria gonorrhoeae, Neisseria meningitidis and Chlamydia pneumoniae.

Respuesta inmune intratecal y características clínicas de la meningoencefalitis por Neisseria meningitidis en pacientes inmunizados con la vacuna cubana VA-MENGOC-BC®

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Elena Noris-García

2008-08-01

Full Text Available La morbimortalidad por la enfermedad meningocócica en Cuba disminuyó notablemente después de la introducción de la vacuna VA-MENGOC-BC®. Sin embargo, años después de ser vacunados se han reportado algunos niños que enfermaron. En este trabajo nos propusimos describir el comportamiento neuroinmunológico y clínico de esta enfermedad en 12 pacientes vacunados que fueron ingresados en el Hospital Pediátrico de San Miguel del Padrón con el diagnóstico de meningoencefalitis producida por Neisseria meningitidis. Se tomaron muestras de forma simultánea de sangre y líquido cefalorraquídeo para la cuantificación de albúmina e inmunoglobulinas mayores por inmunodifusión radial; para el análisis de los resultados se tomó como referencia el registro histórico de los resultados de ocho pacientes no inmunizados que enfermaron antes de incluir esta vacuna en el Esquema Nacional de Vacunación. La respuesta neuroinmunológica y las características clínicas de los pacientes vacunados resultaron diferentes a lo observado previamente en pacientes no vacunados. El grupo vacunado mostró un cuadro menos grave de la enfermedad. El patrón de síntesis intratecal de inmunoglobulinas fue diferente entre los dos grupos. La media de la síntesis intratecal de IgG, IgM e IgA fue significativamente superior en el grupo de los pacientes no vacunados. Este estudio nos permitió concluir que en la muestra estudiada la vacuna modificó la respuesta neuroinmunológica y el cuadro clínico de la enfermedad.

Meningococcal Carriage among College Freshmen in Kashmir, North India- A Single Centre Study

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Nargis K Bali

2017-10-01

Full Text Available Introduction: Data on the community carriage of meningococci in developing countries are sparse. Knowledge about the same would help identify demographic and socio-behavioural risk factors, the need for infection control strategies and the composition of the relevant serogroup for locally effective meningococcal vaccine. Aim: To assess the meningococcal carriage and the major serotypes among fresh college hostellers. Materials and Methods: Charcoal-impregnated nasopharyngeal swabs were collected from 274 consenting fresh college recruits (first year students residing in the college hostel and plated on to Thayer-Martin medium. Oxidase-positive diplococci were taken as presumptive Neisseria species. DNA was extracted from the isolates and Sanger sequencing was performed on the amplified PCR product. Blast analysis of all sequenced samples was performed against the retrieved Neisseria meningitidis sequences from whole NCBI-nr/nt database and within the dataset. Phylogentic analysis was done by Mega-6 professional package comparing published sequences of serogroups against the detected Neisseria meningitidis. Results: Ten (3.6% samples grew oxidase-positive diplococci suggestive of Neisseria. On molecular testing and sequence analysis, 4 samples were found to be N.meningitidis, one (Neisseria spp had close similarity to N.meningitidis and the others included N.perflava (n= 3, N.pharyngis (n=1 and N. flavescens (n=1. N.meningitidis isolates on blast and phylogenetic analysis bore molecular homology to serogroup B. Conclusion: Nasal carriage of N. meningitis (serogroup B was found in about 1.5% (n=4 of the fresh college recruits in the present study. Close proximity amongst the hostellers is likely to result in transmission and such preventive strategies for infection control are desirable. Further, studies of similar kind are mandated to determine the appropriate serogroups required for inclusion in the vaccine.

Activation of Exogenous Fatty Acids to Acyl-Acyl Carrier Protein Cannot Bypass FabI Inhibition in Neisseria*

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Yao, Jiangwei; Bruhn, David F.; Frank, Matthew W.; Lee, Richard E.; Rock, Charles O.

2016-01-01

Neisseria is a Gram-negative pathogen with phospholipids composed of straight chain saturated and monounsaturated fatty acids, the ability to incorporate exogenous fatty acids, and lipopolysaccharides that are not essential. The FabI inhibitor, AFN-1252, was deployed as a chemical biology tool to determine whether Neisseria can bypass the inhibition of fatty acid synthesis by incorporating exogenous fatty acids. Neisseria encodes a functional FabI that was potently inhibited by AFN-1252. AFN-1252 caused a dose-dependent inhibition of fatty acid synthesis in growing Neisseria, a delayed inhibition of growth phenotype, and minimal inhibition of DNA, RNA, and protein synthesis, showing that its mode of action is through inhibiting fatty acid synthesis. Isotopic fatty acid labeling experiments showed that Neisseria encodes the ability to incorporate exogenous fatty acids into its phospholipids by an acyl-acyl carrier protein-dependent pathway. However, AFN-1252 remained an effective antibacterial when Neisseria were supplemented with exogenous fatty acids. These results demonstrate that extracellular fatty acids are activated by an acyl-acyl carrier protein synthetase (AasN) and validate type II fatty acid synthesis (FabI) as a therapeutic target against Neisseria. PMID:26567338

Proteomics of Neisseria gonorrhoeae: the treasure hunt for countermeasures against an old disease

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Benjamin I Baarda

2015-10-01

Full Text Available Neisseria gonorrhoeae is an exquisitely adapted, strictly human pathogen and the causative agent of the sexually transmitted infection gonorrhea. This ancient human disease remains a serious problem, occurring at high incidence globally and having a major impact on reproductive and neonatal health. N. gonorrhoeae is rapidly evolving into a superbug and no effective vaccine exists to prevent gonococcal infections. Untreated or inadequately treated gonorrhea can lead to severe sequelae, including pelvic inflammatory disease and infertility in women, epididymitis in men, and sight- threatening conjunctivitis in infants born to infected mothers. Therefore, there is an immediate need for accelerated research toward the identification of molecular targets for development of drugs with new mechanisms of action and preventive vaccine(s. Global proteomic approaches are ideally suited to guide these studies. Recent quantitative proteomics (SILAC, iTRAQ, and ICAT have illuminated the pathways utilized by N. gonorrhoeae to adapt to different lifestyles and micro-ecological niches within the host, while comparative 2D SDS-PAGE analysis has been used to elucidate spectinomycin resistance mechanisms. Further, high-throughput examinations of cell envelopes and naturally released membrane vesicles have unveiled the ubiquitous and differentially expressed proteins between temporally and geographically diverse N. gonorrhoeae isolates. This review will focus on these different approaches, emphasizing the role of proteomics in the search for vaccine candidates. Although our knowledge of N. gonorrhoeae has been expanded, still far less is known about this bacterium than the closely related N. meningitidis, where genomics- and proteomics-driven studies have led to the successful development of vaccines.

Neisseria meningitidis. Lipopolysakkariders patofysiologiske rolle ved meningokoksygdom og septisk shock

DEFF Research Database (Denmark)

Pedersen, Mie Østergaard; Pedersen, Dan Sonne; Pedersen, Michael

2008-01-01

increased the likelihood of developing an anti-meningococcal immunization strategy based upon the virulence of LPS which may lead to a vaccination against this important pathogen including serogroup B disease. This review summarizes recent findings that may provide a safe, effective prophylaxis and therapy...

Diagnosis of Neisseria gonorrhoeae among pregnant women by culture method and PCR on cppB gene

Directory of Open Access Journals (Sweden)

Jalal Mardaneh

2013-11-01

Full Text Available Background: Neisseria gonorrhoeae is a human obligate pathogen and the etiological agent of gonorrhea. Health irreparable complications resulting from gonorrhea disease occur mainly in pregnant women and neonates. Aim of this study was diagnosis of Neisseria gonorrhoeae among pregnant women with using culture and molecular method by amplification of cppB gene with PCR. Material and Methods: In this cross-sectional study, two endocervical swab specimens were obtained from 1100 pregnant women who referred to Shiraz Hospitals. Culture on nonselective and selective media and nucleic acid amplification test (NAAT were performed for detection of Neisseria gonorrhoeae cppB gene. Results: All endocervical swabs cultures on selective and nonselective media were negative for Neisseria gonorrhoeae. Among examined endocervical swabs, 13samples (1.18% were positive by nucleic acid amplification of Neisseria gonorrgoeae cppB gene. Conclusion: Negative results of culture and positive results of PCR in this study indicate that however culture is gold standard method for detection of Neisseria gonorrhoeae but due to bacterial autolysis, poor sampling techniques and improper specimen storage and transport, its value decline as compared with Nucleic acid amplification test (NAAT.

The role and regulation of catalase in respiratory tract opportunistic bacterial pathogens.

Science.gov (United States)

Eason, Mia M; Fan, Xin

2014-09-01

Respiratory tract bacterial pathogens are the etiologic agents of a variety of illnesses. The ability of these bacteria to cause disease is imparted through survival within the host and avoidance of pathogen clearance by the immune system. Respiratory tract pathogens are continually bombarded by reactive oxygen species (ROS), which may be produced by competing bacteria, normal metabolic function, or host immunological responses. In order to survive and proliferate, bacteria have adapted defense mechanisms to circumvent the effects of ROS. Bacteria employ the use of anti-oxidant enzymes, catalases and catalase-peroxidases, to relieve the effects of the oxidative stressors to which they are continually exposed. The decomposition of ROS has been shown to provide favorable conditions in which respiratory tract opportunistic bacterial pathogens such as Haemophilus influenzae, Mycobacterium tuberculosis, Legionella pneumophila, and Neisseria meningitidis are able to withstand exposure to highly reactive molecules and yet survive. Bacteria possessing mutations in the catalase gene have a decreased survival rate, yet may be able to compensate for the lack of catalatic activity if peroxidatic activity is present. An incomplete knowledge of the mechanisms by which catalase and catalase-peroxidases are regulated still persists, however, in some bacterial species, a regulatory factor known as OxyR has been shown to either up-regulate or down-regulate catalase gene expression. Yet, more research is still needed to increase the knowledge base in relation to this enzyme class. As with this review, we focus on major respiratory tract opportunistic bacterial pathogens in order to elucidate the function and regulation of catalases. The importance of the research could lead to the development of novel treatments against respiratory bacterial infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

Duplex recombinase polymerase amplification assays incorporating competitive internal controls for bacterial meningitis detection.

Science.gov (United States)

Higgins, Owen; Clancy, Eoin; Forrest, Matthew S; Piepenburg, Olaf; Cormican, Martin; Boo, Teck Wee; O'Sullivan, Nicola; McGuinness, Claire; Cafferty, Deirdre; Cunney, Robert; Smith, Terry J

2018-04-01

Recombinase polymerase amplification (RPA) is an isothermal nucleic acid amplification technology that provides rapid and robust infectious disease pathogen detection, ideal for point-of-care (POC) diagnostics in disease-prevalent low-resource countries. We have developed and evaluated three duplex RPA assays incorporating competitive internal controls for the detection of leading bacterial meningitis pathogens. Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae singleplex RPA assays were initially developed and evaluated, demonstrating 100% specificity with limits of detection of 4.1, 8.5 and 3.9 genome copies per reaction, respectively. Each assay was further developed into internally controlled duplex RPA assays via the incorporation of internal amplification control templates. Clinical performance of each internally controlled duplex RPA assay was evaluated by testing 64 archived PCR-positive clinical samples. Compared to real-time PCR, all duplex RPA assays demonstrated 100% diagnostic specificity, with diagnostic sensitivities of 100%, 86.3% and 100% for the S. pneumoniae, N. meningitidis and H. influenzae assays, respectively. This study details the first report of internally controlled duplex RPA assays for the detection of bacterial meningitis pathogens: S. pneumoniae, N. meningitidis and H. influenzae. We have successfully demonstrated the clinical diagnostic utility of each duplex RPA assay, introducing effective diagnostic technology for POC bacterial meningitis identification in disease-prevalent developing countries. Copyright © 2018 Elsevier Inc. All rights reserved.

Meningococcemia crónica Chronic menigococcemia

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Jorge V. Martínez

2008-08-01

Full Text Available La meningococcemia crónica es una forma clínica infrecuente dentro del espectro de infecciones producido por Neisseria meningitidis. Clásicamente esta forma clínica se caracteriza por fiebre, lesiones cutáneas, compromiso articular, y desarrollo en hemocultivo de la bacteria responsable, habitualmente con ausencia de compromiso meníngeo. Generalmente afecta a adultos jóvenes previamente sanos. Se desconoce la razón por la cual estos pacientes, a diferencia de los que presentan meningitis aguda por Neisseria meningitidis y meningococcemia aguda, pueden sobrevivir sin complicaciones durante semanas en ausencia de tratamiento antibiótico útil. Se ha planteado que debido a la alta sensibilidad de esta bacteria a los antibióticos beta-lactámicos, muchos casos podrían ser tratados inadvertidamente. Describimos un caso de meningococcemia crónica en una mujer joven que presenta un cuadro clásico no reconocido inicialmente.Chronic meningococcemia is an unfrequent clinical picture within the spectrum of infections produced by Neisseria meningitidis. It is classically characterized by fever, skin lesions and joint involvement, usually without meningeal involvement, and with blood culture growth of the responsible bacteria. It generally affects previously healthy young people. It is unknown why these patients, unlike patients with Neisseria meningitidis’s acute meningitis and with acute meningococcemia, can survive without complications during weeks, in abscence of an useful antibiotic treatment. It has been hypothesized that owing to high susceptibility to beta-lactam antibiotics of Neisseria meningitidis, many cases may be treated inadvertently. We describe a case of chronic meningococcemia in a young woman who presented a classical clinical picture, not recognized initially.

Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

Science.gov (United States)

Bielecka, Magdalena K.; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E.

2014-01-01

A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human proteins, we immunized mice with recombinant truncated type I rMIP proteins that lacked the globular domain and the signal leader peptide (LP) signal sequence (amino acids 1 to 22) and contained the His purification tag at either the N or C terminus (C-term). The immunogenicity of truncated rMIP proteins was compared to that of full (i.e., full-length) rMIP proteins (containing the globular domain) with either an N- or C-terminal His tag and with or without the LP sequence. By comparing the functional murine antibody responses to these various constructs, we determined that C-term His truncated rMIP (−LP) delivered in liposomes induced high levels of antibodies that bound to the surface of wild-type but not Δmip mutant meningococci and showed bactericidal activity against homologous type I MIP (median titers of 128 to 256) and heterologous type II and III (median titers of 256 to 512) strains, thereby providing at least 82% serogroup B strain coverage. In contrast, in constructs lacking the LP, placement of the His tag at the N terminus appeared to abrogate bactericidal activity. The strategy used in this study would obviate any potential concerns regarding the use of MIP antigens for inclusion in bacterial vaccines. PMID:25452551

Recombinant protein truncation strategy for inducing bactericidal antibodies to the macrophage infectivity potentiator protein of Neisseria meningitidis and circumventing potential cross-reactivity with human FK506-binding proteins.

Science.gov (United States)

Bielecka, Magdalena K; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E; Christodoulides, Myron

2015-02-01

A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human proteins, we immunized mice with recombinant truncated type I rMIP proteins that lacked the globular domain and the signal leader peptide (LP) signal sequence (amino acids 1 to 22) and contained the His purification tag at either the N or C terminus (C-term). The immunogenicity of truncated rMIP proteins was compared to that of full (i.e., full-length) rMIP proteins (containing the globular domain) with either an N- or C-terminal His tag and with or without the LP sequence. By comparing the functional murine antibody responses to these various constructs, we determined that C-term His truncated rMIP (-LP) delivered in liposomes induced high levels of antibodies that bound to the surface of wild-type but not Δmip mutant meningococci and showed bactericidal activity against homologous type I MIP (median titers of 128 to 256) and heterologous type II and III (median titers of 256 to 512) strains, thereby providing at least 82% serogroup B strain coverage. In contrast, in constructs lacking the LP, placement of the His tag at the N terminus appeared to abrogate bactericidal activity. The strategy used in this study would obviate any potential concerns regarding the use of MIP antigens for inclusion in bacterial vaccines. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The prevalence of side-effects: ciprofloxacin 500 mg single dose ...

African Journals Online (AJOL)

Potchefstroom experienced an outbreak of Neisseria meningitidis (N. meningitidis) during May-July 2003. An opportunity for obtaining valuable data arose when mass prophylactic treatment to approximately 28% of the Potchefstroom community was provided by the Department of Health, North-West Province. The aim of ...

Mannose-Binding Lectin Gene, MBL2, Polymorphisms Do Not Increase Susceptibility to Invasive Meningococcal Disease in a Population of Danish Children

DEFF Research Database (Denmark)

Lundbo, Lene F; Sørensen, Henrik T.; Clausen, Louise Nygaard

2015-01-01

of the innate immune system may predispose to invasive meningococcal disease (IMD). In this study, we investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, and its promoter on susceptibility to IMD and IMD-associated mortality among children. Methods.  Children (...Background.  Neisseria meningitidis is the cause of meningococcal bacteremia and meningitis, and nasopharyngeal colonization with this pathogen is common. The incidence of invasive disease is highest in infants, whereas adolescents more often are carriers. Altered regulation or dysfunction...

Caracterización de aislamientos invasivos de S. pneumoniae, H. influenzae y N. meningitidis en América Latina y el Caribe: SIREVA II, 2000-2005 Characterization of invasive isolates of S. pneumoniae, H. influenzae, and N. meningitidis in Latin America and the Caribbean: SIREVA II, 2000-2005

Directory of Open Access Journals (Sweden)

Jean-Marc Gabastou

2008-07-01

Full Text Available OBJETIVOS: Analizar las características fenotípicas y la susceptibilidad a antibióticos de las cepas circulantes de Streptococcus pneumoniae, Haemophilus influenzae y Neisseria meningitidis en América Latina y el Caribe entre 2000 y 2005. Se evaluó la cobertura potencial de las vacunas conjugadas. MÉTODOS: Se estudió por métodos convencionales la distribución de los serotipos o serogrupos de 17 303 cepas de S. pneumoniae, 2 782 cepas de H. influenzae y 6 955 cepas de N. meningitidis aisladas de casos de neumonía, meningitis, sepsis, bacteriemias y otros procesos invasivos. Se evaluó la susceptibilidad a los antibióticos de las cepas estudiadas. Los aislamientos procedían de 453 centros centinelas de 19 países de América Latina y 4 del Caribe, como parte del proyecto SIREVA II. RESULTADOS: El serotipo 14 de S. pneumoniae fue el más frecuentemente aislado (21,1%, especialmente en niños menores de 6 años (29,1%. Las coberturas potenciales de las vacunas conjugadas antineumocócicas hepta, nona, deca y tridecavalentes fueron de 59,0%, 73,4%, 76,5% y 85,9%, respectivamente. De los aislamientos, 63,3% eran sensibles a la penicilina. El serotipo b de H. influenzae estuvo presente en 72,2% de los aislamientos en niños menores de 2 años, mientras 8,6% correspondieron a los serotipos a, c, d, e y f; 19,2% resultaron no serotipables. La proporción de cepas de H. influenzae productoras de betalactamasa en aislamientos en niños menores de 2 años fue de 16,3%. Los serogrupos de N. meningitidis más frecuentes fueron el B (69,0% y el C (25,7%; 65,8% y 99,2% de las cepas fueron sensibles a la penicilina y a la rifampicina, respectivamente. CONCLUSIONES: Estos resultados resaltan la importancia de la vigilancia epidemiológica integral de S. pneumoniae, H. influenzae y N. meningitidis en América Latina y el Caribe. La gran heterogeneidad en la distribución de los serotipos de S. pneumoniae en los países estudiados podría reducir la

NeisseriaBase: a specialised Neisseria genomic resource and analysis platform

OpenAIRE

Wenning Zheng; Naresh V.R. Mutha; Hamed Heydari; Avirup Dutta; Cheuk Chuen Siow; Nicholas S. Jakubovics; Wei Yee Wee; Shi Yang Tan; Mia Yang Ang; Guat Jah Wong; Siew Woh Choo

2016-01-01

Background. The gram-negative Neisseria is associated with two of the most potent human epidemic diseases: meningococcal meningitis and gonorrhoea. In both cases, disease is caused by bacteria colonizing human mucosal membrane surfaces. Overall, the genus shows great diversity and genetic variation mainly due to its ability to acquire and incorporate genetic material from a diverse range of sources through horizontal gene transfer. Although a number of databases exist for the Neisseria genome...

Production of 14C-labeled gas in BACTEC Neisseria Differentiation kits by Neisseria cinerea

International Nuclear Information System (INIS)

Boyce, J.M.; Mitchell, E.B. Jr.; Knapp, J.S.; Buttke, T.M.

1985-01-01

Six strains of Neisseria cinerea were tested in BACTEC Neisseria Differentiation kits (Johnston Laboratories, Inc., Towson, Md.), and all yielded positive glucose growth indices and negative maltose and fructose growth indices. These results were similar to those achieved with Neisseria gonorrhoeae. However, most of the N. cinerea isolates tested yielded 3-h glucose growth indices that were lower than those obtained with gonococci. 14 C-labeled gas was produced significantly faster by N. gonorrhoeae than by N. cinerea. Additional studies suggested that the 14 C-labeled gas produced by N. cinerea was carbon dioxide. N. cinerea strains were similar to Branhamella catarrhalis strains because both species failed to produce detectable acid from glucose, maltose, sucrose, fructose, and lactose in cysteine-tryptic agar media. However, in contrast to N. cinerea strains, B. catarrhalis strains did not metabolize glucose in BACTEC Neisseria Differentiation kits

Influenza interaction with cocirculating pathogens and its impact on surveillance, pathogenesis, and epidemic profile: A key role for mathematical modelling.

Directory of Open Access Journals (Sweden)

Lulla Opatowski

2018-02-01

Full Text Available Evidence is mounting that influenza virus interacts with other pathogens colonising or infecting the human respiratory tract. Taking into account interactions with other pathogens may be critical to determining the real influenza burden and the full impact of public health policies targeting influenza. This is particularly true for mathematical modelling studies, which have become critical in public health decision-making. Yet models usually focus on influenza virus acquisition and infection alone, thereby making broad oversimplifications of pathogen ecology. Herein, we report evidence of influenza virus interactions with bacteria and viruses and systematically review the modelling studies that have incorporated interactions. Despite the many studies examining possible associations between influenza and Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Neisseria meningitidis, respiratory syncytial virus (RSV, human rhinoviruses, human parainfluenza viruses, etc., very few mathematical models have integrated other pathogens alongside influenza. The notable exception is the pneumococcus-influenza interaction, for which several recent modelling studies demonstrate the power of dynamic modelling as an approach to test biological hypotheses on interaction mechanisms and estimate the strength of those interactions. We explore how different interference mechanisms may lead to unexpected incidence trends and possible misinterpretation, and we illustrate the impact of interactions on public health surveillance using simple transmission models. We demonstrate that the development of multipathogen models is essential to assessing the true public health burden of influenza and that it is needed to help improve planning and evaluation of control measures. Finally, we identify the public health, surveillance, modelling, and biological challenges and propose avenues of research for the coming years.

Meningococcal genetic variation mechanisms viewed through comparative analysis of serogroup C strain FAM18.

Directory of Open Access Journals (Sweden)

Stephen D Bentley

2007-02-01

Full Text Available The bacterium Neisseria meningitidis is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Occasionally strains can invade host tissues causing septicaemia and meningitis, making the bacterium a major cause of morbidity and mortality in both the developed and developing world. The species is known to be diverse in many ways, as a product of its natural transformability and of a range of recombination and mutation-based systems. Previous work on pathogenic Neisseria has identified several mechanisms for the generation of diversity of surface structures, including phase variation based on slippage-like mechanisms and sequence conversion of expressed genes using information from silent loci. Comparison of the genome sequences of two N. meningitidis strains, serogroup B MC58 and serogroup A Z2491, suggested further mechanisms of variation, including C-terminal exchange in specific genes and enhanced localised recombination and variation related to repeat arrays. We have sequenced the genome of N. meningitidis strain FAM18, a representative of the ST-11/ET-37 complex, providing the first genome sequence for the disease-causing serogroup C meningococci; it has 1,976 predicted genes, of which 60 do not have orthologues in the previously sequenced serogroup A or B strains. Through genome comparison with Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in N. meningitidis, describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in N. meningitidis. Our analysis provides evidence for the hypothesis that the noncoding repeat arrays in neisserial genomes (neisserial intergenic mosaic elements provide a crucial mechanism for the generation of surface antigen variants. Such variation will have an

Proteoliposome derived cochleate as novel adjuvant.

Science.gov (United States)

Bracho, Gustavo; Lastre, Miriam; del Campo, Judith; Zayas, Caridad; González, Domingo; Gil, Danay; Acevedo, Reinaldo; Taboada, Carlos; Solís, Rosa L; Pérez, Oliver

2006-04-12

Cochleate structures (CS) consist in a highly stable lipid structures that have been reported to be a good antigen delivery system. The incorporation of pathogen associated molecular pattern (PAMP) from bacterial membranes into CS became in a promising approach to develop adjuvants, particularly mucosal adjuvants. Therefore, we prepare CS from proteoliposome (PL) obtained from Neisseria meningitidis B (PLCS) and evaluated it for its capability to stimulate the immune system as well as the adjuvant activity. The ability of PLCS to induce Thl polarization was also explored. The results and the easy capability for new antigen incorporation on CS support its use as adjuvant for immunization with a large variety of pathogen derived antigens and different routes of immunization.

Risk factors for community-acquired bacterial meningitis

DEFF Research Database (Denmark)

Lundbo, Lene Fogt; Benfield, Thomas

2017-01-01

of these are pathogen-specific, while some are shared between different bacteria. METHODS: We searched the database PubMed to identify host risk factors for bacterial meningitis caused by the pathogens Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b, because they are three most common...... causative bacteria beyond the neonatal period. RESULTS: We describe a number of risk factors; including socioeconomic factors, age, genetic variation of the host and underlying medical conditions associated with increased susceptibility to invasive bacterial infections in both children and adults....... CONCLUSIONS: As conjugated vaccines are available for these infections, it is of utmost importance to identify high risk patients to be able to prevent invasive disease....

An unusual case of neonatal meningococcal meningitis complicated ...

African Journals Online (AJOL)

Neisseria meningitidis is a leading cause of pyogenic meningitis worldwide, as well as causing large epidemics in parts of Africa. With the dramatic decline in cases of Haemophilus inuenzae B, N. meningitidis has emerged as one of the most common causes of acute bacterial meningitis in children and adults in South ...

Characteristics of pathogenic Neisseria meningitidis in Moscow: prevalence of 'non-European' strains

NARCIS (Netherlands)

Koroleva, Irina S.; Platonov, Alexander E.; van der Ende, Arie; Kuijper, Ed; Dankert, Jacob

1998-01-01

OBJECTIVE: To investigate the distribution of serogroups, serotypes and subtypes, and susceptibility to antibiotics, of 75 strains isolated from patients with systemic meningococcal disease in Moscow in 1993--95. RESULTS: In contrast to the situation in most European countries, 21% of group A

Safety and immunogenocity of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old.

Science.gov (United States)

Hu, Jian-li; Tao, Hong; Li, Jing-xin; Dai, Wei-ming; Song, Bin; Sun, Jin-fang; Liu, Pei; Tang, Jie; Liu, Wen-yu; Wang, Shi-yuan; Zhu, Feng-cai

2015-01-01

A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6-23 months and in a single dose to children aged 2-5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6-23 months was 46.8% and that in vaccinees aged 2-5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ≥ 1:8 and PRP ≥ 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases.

Surveillance for Neisseria meningitidis Disease Activity and Transmission Using Information Technology.

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S Sohail Ahmed

Full Text Available While formal reporting, surveillance, and response structures remain essential to protecting public health, a new generation of freely accessible, online, and real-time informatics tools for disease tracking are expanding the ability to raise earlier public awareness of emerging disease threats. The rationale for this study is to test the hypothesis that the HealthMap informatics tools can complement epidemiological data captured by traditional surveillance monitoring systems for meningitis due to Neisseria meningitides (N. meningitides by highlighting severe transmissible disease activity and outbreaks in the United States.Annual analyses of N. meningitides disease alerts captured by HealthMap were compared to epidemiological data captured by the Centers for Disease Control's Active Bacterial Core surveillance (ABCs for N. meningitides. Morbidity and mortality case reports were measured annually from 2010 to 2013 (HealthMap and 2005 to 2012 (ABCs.HealthMap N. meningitides monitoring captured 80-90% of alerts as diagnosed N. meningitides, 5-20% of alerts as suspected cases, and 5-10% of alerts as related news articles. HealthMap disease alert activity for emerging disease threats related to N. meningitides were in agreement with patterns identified historically using traditional surveillance systems. HealthMap's strength lies in its ability to provide a cumulative "snapshot" of weak signals that allows for rapid dissemination of knowledge and earlier public awareness of potential outbreak status while formal testing and confirmation for specific serotypes is ongoing by public health authorities.The underreporting of disease cases in internet-based data streaming makes inadequate any comparison to epidemiological trends illustrated by the more comprehensive ABCs network published by the Centers for Disease Control. However, the expected delays in compiling confirmatory reports by traditional surveillance systems (at the time of writing, ABCs data

Estandarización de ensayos inmunoenzimáticos (ELISA para la cuantificación de anticuerpos IgG inducidos por una vacuna de vesículas de membrana externa de los serogrupos A y W135 de Neisseria meningitidis

Directory of Open Access Journals (Sweden)

Aleida Mandiarote

2013-04-01

Full Text Available La enfermedad meningocócica es una afección invasiva, de amplia incidencia mundial, cuyo agente causal es la bacteria gramnegativa Neisseria meningitidis . Existen vacunas polisacarídicas sin conjugar o conjugadas, contra cuatro de los cinco serogrupos responsables del 95% de los casos en el mundo. Para el serogrupo B, cuyo polisacárido es pobremente inmunogénico, se han evaluado varios candidatos vacunales producidos a base de vesículas de membrana externa. La determinación de la actividad bactericida y la cuantificación de IgG por ELISA han sido los métodos más utilizados en la medición de la respuesta inmune generada por vacunas contra la meningitis meningocócica. El segundo de estos métodos es utilizado en el Instituto Finlay como ensayo de inmunogenicidad para la liberación de lotes de VA-MENGOC-BC®. Como parte de una colaboración con investigadores noruegos, se trabaja en la obtención de un candidato vacunal contra los serogrupos A y W135 , basado en vesículas de membrana externa. En el presente trabajo se describe la estandarización de un ELISA para ser utilizado en la evaluación de la respuesta inmune del candidato vacunal bivalente.

ORF Alignment: NC_003116 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available ... - Neisseria meningitidis (strain Z2491 serogroup A) ... Length = 372 ... Query: 1 ... MKIGIPRESLSGETRVACTPAT...VALLGKLGFETVVEXXXXXXXXXXXXXXXXXXXXXXXX 60 ... MKIGIPRESLSGETRVACTPATVALLGKLGFETVVE ... ... ... Sbjct: 1 ... MKIGIPRESLSGETRVACTPATVALLGKLGFETVVESGAGLAASLDDAAYQAAGAT

A comparison of meningococcal carriage by pregnancy status

Directory of Open Access Journals (Sweden)

Knudtson Eric J

2010-08-01

Full Text Available Abstract Neisseria meningitidis is the second leading cause of invasive meningitis. A prerequisite for infection is colonization of the nasopharynx, and asymptomatic carrier rates are widely reported in the range of 10-15%. Recent reports have indicated an increased likelihood that a pediatric admission for Neisseria meningitidis will have a mother who is pregnant in the home. We hypothesized that this association may relate to immunologic changes in pregnancy leading to higher carrier rates. We compared the carrier status by performing nasopharyngeal swabs for Neisseria meningitidis in 100 pregnant and 99 non-pregnant women. Average age of the participants was 28.9 +/- 6.7 years. The average gestational age at specimen collection was 27.5 +/- 9.4 weeks. Non pregnant women were significantly more likely to use tobacco (38% vs 24%, p The meningococcal carrier rate in our population is well below what is widely reported in the literature. Assuming a 1% carrier rate in the pregnant group and a 0.5% carrier rate in the non pregnant group, 4,763 patients would be required to detect a difference of this magnitude, given 80% power and an alpha of 0.05.

ORF Alignment: NC_003112 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available IEFEPFTYAYEEHGGTAQFARLFGKDEHLVIKTIVLQDENGKGLIVLMH 68 ... TPAVRVLRENGIEFEPFTY...AYEEHGGTAQFARLFGKDEHLVIKTIVLQDENGKGLIVLMH Sbjct: 1 ... TPAVRVLRENGIEFEPFTYAYEEHGGTAQFARLFGKDEHLVIKTIVLQDENGKGL...l protein ... NMB1026 [Neisseria meningitidis MC58] ... Length = 139 ... Query: 9 ... TPAVRVLRENG

Seroprevalence and placental transmission of maternal antibodies specific for Neisseria meningitidis Serogroups A, C, Y and W135 and influence of maternal antibodies on the immune response to a primary course of MenACWY-CRM vaccine in the United Kingdom.

Science.gov (United States)

Blanchard-Rohner, Geraldine; Snape, Matthew D; Kelly, Dominic F; O'Connor, Daniel; John, Tessa; Kibwana, Elizabeth; Parks, Hannah; Ford, Karen; Dull, Peter M; Pollard, Andrew J

2013-07-01

Maternal antibodies give neonates some protection against bacterial infection. We measured antibodies against Neisseria meningitidis serogroups A, C, Y and W135 in mothers and their 2-month-old infants at study enrollment. We also assessed the impact of maternal antibody present at 2 months of age on the immune response to a primary course of quadrivalent meningococcal conjugate vaccine (MenACWY-CRM197) given at 2 and 4 months of age. This was a single-center, open-label, randomized study undertaken in Oxford, United Kingdom. Two hundred sixteen healthy infants were enrolled in the study and vaccinated with MenACWY-CRM197 at 2 and 4 months of age. Blood was obtained from all mothers, in a subset of infants at 2 months and all infants at 5 months. Antibody and memory B-cell responses at 5 months were correlated with maternal antibodies. Mothers had low IgG antibodies against serogroups C, W135 and Y polysaccharides, but high serogroup A antibody, whereas 61-78% had protective human complement serum bactericidal activity (hSBA) (≥1:4) for serogroups C, W135 and Y but only 31% for serogroup A. Only 9%, 32%, 45% and 19% of 2-month-old infants had hSBA ≥1:4 for serogroups A, C, W135 and Y, respectively. Maternal antibody had little association on responses to MenACWY-CRM197, except a moderate negative association between MenC-specific bactericidal antibody at 2 and 5 months (r = -0.5, P = 0.006, n = 28) and between carrier-specific IgG antibody at 2 months and MenC-specific hSBA/IgG antibody at 5 months (r = -0.4, P = 0.02 and 0.04, n = 32 and 23). Nonetheless, 90% of infants achieved protective MenC-hSBA titers after vaccination at 2 and 4 months of age. The levels of serogroup-specific meningococcal antibodies were low in mothers and 2-month-old infants. Immunizing mothers before or during pregnancy with meningococcal conjugate vaccines might increase antibody levels in early infancy and provide protection against infection due to N. meningitidis.

A New Family of Capsule Polymerases Generates Teichoic Acid-Like Capsule Polymers in Gram-Negative Pathogens.

Science.gov (United States)

Litschko, Christa; Oldrini, Davide; Budde, Insa; Berger, Monika; Meens, Jochen; Gerardy-Schahn, Rita; Berti, Francesco; Schubert, Mario; Fiebig, Timm

2018-05-29

Group 2 capsule polymers represent crucial virulence factors of Gram-negative pathogenic bacteria. They are synthesized by enzymes called capsule polymerases. In this report, we describe a new family of polymerases that combine glycosyltransferase and hexose- and polyol-phosphate transferase activity to generate complex poly(oligosaccharide phosphate) and poly(glycosylpolyol phosphate) polymers, the latter of which display similarity to wall teichoic acid (WTA), a cell wall component of Gram-positive bacteria. Using modeling and multiple-sequence alignment, we showed homology between the predicted polymerase domains and WTA type I biosynthesis enzymes, creating a link between Gram-negative and Gram-positive cell wall biosynthesis processes. The polymerases of the new family are highly abundant and found in a variety of capsule-expressing pathogens such as Neisseria meningitidis , Actinobacillus pleuropneumoniae , Haemophilus influenzae , Bibersteinia trehalosi , and Escherichia coli with both human and animal hosts. Five representative candidates were purified, their activities were confirmed using nuclear magnetic resonance (NMR) spectroscopy, and their predicted folds were validated by site-directed mutagenesis. IMPORTANCE Bacterial capsules play an important role in the interaction between a pathogen and the immune system of its host. During the last decade, capsule polymerases have become attractive tools for the production of capsule polymers applied as antigens in glycoconjugate vaccine formulations. Conventional production of glycoconjugate vaccines requires the cultivation of the pathogen and thus the highest biosafety standards, leading to tremendous costs. With regard to animal husbandry, where vaccines could avoid the extensive use of antibiotics, conventional production is not sufficiently cost-effective. In contrast, enzymatic synthesis of capsule polymers is pathogen-free and fast, offers high stereo- and regioselectivity, and works with high efficacy

Meningitis - meningococcal

Science.gov (United States)

Meningococcal meningitis; Gram negative - meningococcus ... Meningococcal meningitis is caused by the bacteria Neisseria meningitidis (also known as meningococcus). Meningococcus is the most common cause ...

ORF Alignment: NC_003112 [GENIUS II[Archive

Lifescience Database Archive (English)

Full Text Available otein RecO [Neisseria meningitidis MC58] ... Length = 233 ... Query: 5 ... RVNHEPVFMLASSPWRESSLWVEAFSRRYGRVALLARSARKRQSELRGVLVPFVPV...SVSW 64 ... RVNHEPVFMLASSPWRESSLWVEAFSRRYGRVALLARSARKRQSELRGVLVPFVPVSVSW Sbj...ct: 1 ... RVNHEPVFMLASSPWRESSLWVEAFSRRYGRVALLARSARKRQSELRGVLVPFVPVSVSW 60 ... Query: 1

Epidemiology of paediatric meningitis in central Côte d'Ivoire after the implementation of Haemophilus influenzae type b vaccination.

Science.gov (United States)

Touré, Fidèle S; Kouame, Samson; Tia, Honoré; Monemo, Pacôme; Cissé, Amadou; Diané, Bamourou; Becker, Sören L; Akoua-Koffi, Chantal

2017-07-01

Infectious meningitis accounts for enormous morbidity worldwide, but there is a paucity of data on its regional epidemiology in resource-constrained settings of sub-Saharan Africa. Here, we present a study on the aetiology of paediatric meningitis in central Côte d'Ivoire. Between June 2012 and December 2013, all cerebrospinal fluid (CSF) samples drawn at the University Teaching Hospital Bouaké were examined for the presence of bacterial and fungal pathogens. A causative agent was detected in 31 out of 833 CSF specimens (3.7%), with the most prevalent pathogens being Streptococcus pneumoniae (n=15) and Neisseria meningitidis (n=5). With the exception of neonates, these two bacteria were the most common agents in all age groups. Of note, only a single case of Haemophilus influenzae meningitis was detected. Hence, this study reports a considerable shift in the epidemiology of paediatric meningitis in central Côte d'Ivoire. Following the implementation of a nation-wide childhood vaccination programme against H. influenzae type b, this pathogen was much less frequently reported than in previous studies. The integration of specific vaccines against S. pneumoniae and N. meningitidis into the childhood vaccination programme in Côted'Ivoire holds promise to further reduce the burden due to infectious meningitis.

Regulation of iron metabolism during Neisseria meningitidis infection in mice

Energy Technology Data Exchange (ETDEWEB)

Letendre, E.D.

1984-01-01

Bacterial invasion of vertebrates triggers a marked reduction in the levels of iron associated with the plasma transferrin (Tf) pool. This hypoferremic response has been regarded as a host attempt to withhold essential iron from the invading pathogen. The exact nature of the mechanisms involved remains obscure. The kinetics of iron processing by the RE system were studied by labeling the RE compartments with /sup 59/Fe-labeled denatured red blood cells. Uptake and redistribution of the label indicated the RE-processed iron was not returned to the plasma Tf pool during the hypoferremia. Fractionation of hepatic cellular compartments showed that this impaired release of iron resulted from a preferential incorporation of home-derived iron into the intracellular ferritin pool and this produces the hypoferremia. The role of ceruloplasmin (ferroxidase I,EC.1.16.3.1) (Cp) in iron metabolism during meningococcal infection was investigated. Plasma Cp ferroxidase activity was found to increase greatly in mice during the convalescence phase.

Neisseria meningitidis and Escherichia coli are protected from leukocyte phagocytosis by binding to erythrocyte complement receptor 1 in human blood

DEFF Research Database (Denmark)

Brekke, O. L.; Hellerud, B. C.; Christiansen, D.

2011-01-01

The initial interaction of Gram-negative bacteria with erythrocytes and its implications on leukocyte phagocytosis and oxidative burst in human whole blood were examined. Alexa-labeled Escherichia coli, wild-type H44/76 N. meningitidis and the H44/76lpxA lipopolysaccharide (LPS)-deficient mutant...... antagonist (C5aRa) and a complement receptor 1 (CR1)-blocking antibody (3D9) were examined. Most bacteria (80%) immediately bound to erythrocytes. The binding gradually declined over time, with a parallel increase in phagocytosis. Complement inhibition with compstatin reduced erythrocyte binding...... and bacterial C3 opsonization. In contrast, the C5aRa efficiently reduced phagocytosis, but did not affect the binding of bacteria to erythrocytes. The anti-CR1 blocking mAb dose-dependently reduced bacterial binding to erythrocytes to nil, with subsequent increased phagocytosis and oxidative burst. LPS had...

The structural basis of transferrin sequestration by transferrin-binding protein B

Energy Technology Data Exchange (ETDEWEB)

Calmettes, Charles; Alcantara, Joenel; Yu, Rong-Hua; Schryvers, Anthony B.; Moraes, Trevor F. (Toronto); (Calgary)

2012-03-28

Neisseria meningitidis, the causative agent of bacterial meningitis, acquires the essential element iron from the host glycoprotein transferrin during infection through a surface transferrin receptor system composed of proteins TbpA and TbpB. Here we present the crystal structures of TbpB from N. meningitidis in its apo form and in complex with human transferrin. The structure reveals how TbpB sequesters and initiates iron release from human transferrin.

CEACAM3-mediated phagocytosis of human-specific bacterial pathogens involves the adaptor molecule Nck

OpenAIRE

Peterson, Lisa

2010-01-01

Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are exploited by human-specific pathogens to anchor themselves to or invade host cells. Interestingly, human granulocytes express a specific isoform, CEACAM3, that can direct efficient, opsonin-independent phagocytosis of CEACAM-binding Neisseria, Moraxella and Haemophilus species. As opsonin-independent phagocytosis of CEACAM-binding Neisseria depends on Src-family protein tyrosine kinase (PTK) phosphorylation of the CEACAM3 ...

Browse Title Index

African Journals Online (AJOL)

Clavulanic Acid Antibiotics, Abstract PDF. G Uraz, KOK Turhan, HD Binnet. Vol 9, No 1 (2008), Sero-epidemiological evaluation of clonal diversity and antimicrobial susceptibility patterns among Neisseria meningitidis isolates from ...

Time course of radiometric detection of positive blood cultures in childhood

International Nuclear Information System (INIS)

Meadow, W.L.; Schwartz, I.K.

1986-01-01

We have determined the time course of radiometric detection of microbial growth in 2348 positive blood culture specimens obtained at Wyler Children's Hospital during a 5-year interval. Overall 72 and 88% of isolates were detected within 48 and 72 hours after sampling, respectively. For pathogenic organisms aerobic detection was generally more rapid and more inclusive than anaerobic detection. At 48 hours of incubation the detection of six potential pathogens (Salmonella sp., Haemophilus influenzae, Group D streptococci, Neisseria meningitidis, coagulase-negative staphylococci, Candida sp.) was significantly delayed compared with detection of other pathogenic organisms recovered from blood. At 72 hours of incubation the detection rates remained less than 95% for H. influenzae, Staphylococcus aureus, Klebsiella sp., coagulase-negative staphylococci, Group D streptococci and Candida sp. These data should assist clinical decisions regarding duration of antibiotic therapy for the presumptive diagnosis of bacteremia in children

Time course of radiometric detection of positive blood cultures in childhood

Energy Technology Data Exchange (ETDEWEB)

Meadow, W.L.; Schwartz, I.K.

1986-05-01

We have determined the time course of radiometric detection of microbial growth in 2348 positive blood culture specimens obtained at Wyler Children's Hospital during a 5-year interval. Overall 72 and 88% of isolates were detected within 48 and 72 hours after sampling, respectively. For pathogenic organisms aerobic detection was generally more rapid and more inclusive than anaerobic detection. At 48 hours of incubation the detection of six potential pathogens (Salmonella sp., Haemophilus influenzae, Group D streptococci, Neisseria meningitidis, coagulase-negative staphylococci, Candida sp.) was significantly delayed compared with detection of other pathogenic organisms recovered from blood. At 72 hours of incubation the detection rates remained less than 95% for H. influenzae, Staphylococcus aureus, Klebsiella sp., coagulase-negative staphylococci, Group D streptococci and Candida sp. These data should assist clinical decisions regarding duration of antibiotic therapy for the presumptive diagnosis of bacteremia in children.

Epidemiological profile of acute bacterial meningitis in the state of Rio Grande do Norte, Brazil Perfil epidemiológico da meningite bacteriana aguda no estado do Rio Grande do Norte, Brasil

Directory of Open Access Journals (Sweden)

Wallace Andrino da Silva

2010-08-01

Full Text Available INTRODUCTION: Acute bacterial meningitis (ABM remains a public health problem in Brazil. To evaluate the epidemiology of ABM cases at Giselda Trigueiro Hospital, Rio Grande do Norte, a descriptive retrospective survey was conducted covering 2005 to 2008. METHODS: Clinical and laboratory data were collected from the epidemiology department of the hospital and analyzed. RESULTS: Out of 168 ABM cases, 24.4%, 10.7%, and 2.4% were, respectively, caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenza b, and 5.4% by other bacteria. The mean age was 22.48 ± 18.7 years old. CONCLUSIONS: Streptococcus pneumoniae was the main causative pathogen in the young urban population.INTRODUÇÃO: Meningite bacteriana aguda (MBA permanece um problema de saúde pública no Brasil. Para avaliar a epidemiologia da MBA atendida no Hospital Giselda Trigueiro, Rio Grande do Norte, um estudo retrospectivo-descritivo foi realizado de 2005 a 2008. MÉTODOS: Dados clínicos e laboratoriais foram coletados do departamento de epidemiologia hospitalar e analisados. RESULTADOS: Dos 168 casos de MBA, 24,4%, 10,7% e 2,4% foram, respectivamente, causados por Streptococcus pneumoniae, Neisseria meningitidis e Haemophilus influenzae b e 5,4% por outras bactérias. A média da idade foi 22,48 ± 18,7 anos. CONCLUSÕES: Streptococcus pneumoniae foi o principal patógeno causador na população urbana jovem.

Chronic meningococcemia: a rare presentation of meningococcal disease: case report

Directory of Open Access Journals (Sweden)

Antonio Adolfo Guerra Soares Brandão

2012-03-01

Full Text Available Chronic meningococcemia is a rare clinical presentation within the spectrumof infections due to Neisseria meningitidis, which was first described in 1902.It is defined as a chronic and benign meningococcal bacteremia withoutmeningeal signs or symptoms with at least one week’s duration, characterizedby intermittent or continuous fever, polymorphic cutaneous rash, and migratoryarthropathy. The incidence is believed to be around 1:200,000 inhabitants. Itaffects predominantly young people and adults, and it is equally distributedbetween genders. Diagnosis may be challenging in the early stages of thedisease because of the difficulty in isolating Neisseria meningitidis (it reaches74% of positivity in advanced stages. Recently, the use of PCR for detectingNeisseria sp antigen in skin biopsies specimens has been considered for thoseculture-negative cases. The authors report a case of a 54-year-old femalepatient who sought medical attention for a five-day fever followed by arthralgiaand skin lesions predominantly in the lower limbs. The patient progressed toa toxemic clinical status that improved after the administration of antibiotictherapy, which consisted of oxacillin and ceftriaxone. The diagnosis of chronicmeningococcemia was performed after the isolation of Neisseria meningitidisin two different blood sample cultures. This is, to our knowledge, the firstcase of chronic meningococcemia described in Brazil (up to the writing of thisreport.

Quantitative Proteomics Reveals Distinct Differences in the Protein Content of Outer Membrane Vesicle Vaccines

NARCIS (Netherlands)

Waterbeemd, van de B.; Mommen, G.P.M.; Pennings, J.L.A.; Eppink, M.H.M.; Wijffels, R.H.; Pol, van der L.A.; Jong, de A.P.J.M.

2013-01-01

At present, only vaccines containing outer membrane vesicles (OMV) have successfully stopped Neisseria meningitidis serogroup B epidemics. These vaccines however require detergent-extraction to remove endotoxin, which changes immunogenicity and causes production difficulties. To investigate this in

Control of gdhR Expression in Neisseria gonorrhoeae via Autoregulation and a Master Repressor (MtrR of a Drug Efflux Pump Operon

Directory of Open Access Journals (Sweden)

Corinne E. Rouquette-Loughlin

2017-04-01

Full Text Available The MtrCDE efflux pump of Neisseria gonorrhoeae contributes to gonococcal resistance to a number of antibiotics used previously or currently in treatment of gonorrhea, as well as to host-derived antimicrobials that participate in innate defense. Overexpression of the MtrCDE efflux pump increases gonococcal survival and fitness during experimental lower genital tract infection of female mice. Transcription of mtrCDE can be repressed by the DNA-binding protein MtrR, which also acts as a global regulator of genes involved in important metabolic, physiologic, or regulatory processes. Here, we investigated whether a gene downstream of mtrCDE, previously annotated gdhR in Neisseria meningitidis, is a target for regulation by MtrR. In meningococci, GdhR serves as a regulator of genes involved in glucose catabolism, amino acid transport, and biosynthesis, including gdhA, which encodes an l-glutamate dehydrogenase and is located next to gdhR but is transcriptionally divergent. We report here that in N. gonorrhoeae, expression of gdhR is subject to autoregulation by GdhR and direct repression by MtrR. Importantly, loss of GdhR significantly increased gonococcal fitness compared to a complemented mutant strain during experimental murine infection. Interestingly, loss of GdhR did not influence expression of gdhA, as reported for meningococci. This variance is most likely due to differences in promoter localization and utilization between gonococci and meningococci. We propose that transcriptional control of gonococcal genes through the action of MtrR and GdhR contributes to fitness of N. gonorrhoeae during infection.

Audit of antibiotic therapy in surgical neonates in a tertiary hospital ...

African Journals Online (AJOL)

Polymicrobial postoperative wound infections and sepsis caused by Staphylococcus aureus, Escherichia coli, Neisseria meningitidis, Klebsiella pneumonia, Pseudomonas aeroginosa and anaerobes, were mainly encountered. The most common aerobes isolated from wound cultures were S. aureus and P. aeroginosa ...

Overview of the Spleen

Science.gov (United States)

... Neisseria meningitidis , and Haemophilus influenzae . Because of this risk, people receive vaccinations to help protect them from infection with these organisms. People should also be sure they receive the influenza vaccine every year, as is now ... the Spleen ...

Microbial Pathogens Implicated in Reproductive Health Infections in a Special Treatment Clinic in Ibadan, Nigeria

Directory of Open Access Journals (Sweden)

Adenike Ogunshe

2009-03-01

Full Text Available Objective: The lack of adequate recognition of health importance of non-HIV reproductive health infections (RHIs in Nigeria has led into this study, which was to determine clinical pathogens in non-HIV RHI in Nigeria using a tertiary health facility as case study.Materials and Methods: A nine-year investigation was carried out between 1997 and 2005 on 4047 (n = 1626 males; n = 2421 females patients presenting at Special Treatment Clinic (STC of University College Hospital (UCH Ibadan, Nigeria. Routine laboratory procedures using appropriate culture media, culture conditions, and current phenotypic taxonomic tools for classification of isolated pathogens were employed.Results: Age (p = 0.019 and gender (p<0.0001 were related to the recovery rates of pathogens Candida species (55.6 %, Neisseria gonorrhoae (11.1%, Gardenella vaginalis (10.3%, Escherichia coli (9.2 %, Klebsiella sp. (4.2%, streptococci (4.0%, Staphylococcus aureus (2.3%, Proteus sp., (1.8%, Haemophilus ducreyi (0.5%, Trichomonas vaginalis (0.44% and Pseudomonas aeruginosa (0.18%. Candida and Gardenella vaginalis species were mostly recovered from female patients, while N.gonorrhoeae were mostly isolated from male patients. Age brackets for the recovery of pathogens were Neisseria gonorrhoeae (16-30 years; Gardenella vaginalis (21-25 and 31-35 years and C.albicans (21-30 years.Conclusion: Candida, Neisseria gonorrhoea and Gadrenella vaginalis were the most recovered pathogens from patients presenting at Special Treatment Clinic of a tertiary health institution in Nigeria, and the relationship between age, gender and the aetiological agents was statistically significant.

Meningitis registry of hospitalized cases in children: epidemiological patterns of acute bacterial meningitis throughout a 32-year period

Directory of Open Access Journals (Sweden)

Syriopoulou Vassiliki P

2007-08-01

rise of IR in period C. The Case Fatality Rate (CFR from all causes was 3.8%, while higher CFR were estimated for Streptococcus pneumoniae (7.5%, RR=2.1, 95% CI 1.2–3.7 and Neisseria meningitidis (4.8%, RR=1.7, 95% CI 1.1–2.5 compared to other pathogens. Moreover, overall CFR varied significantly among the three time periods (p = 0.0015, and was estimated to be higher in period C. Conclusion By using the MR we were able to delineate long-term changes in the epidemiology of bacterial meningitis. Thus the MR proved to be a useful tool in the study and the prevention of communicable diseases in correlation with prevention strategies, such as vaccinations.

Effect of vaccines on bacterial meningitis worldwide

NARCIS (Netherlands)

McIntyre, Peter B.; O'Brien, Katherine L.; Greenwood, Brian; van de Beek, Diederik

2012-01-01

Three bacteria-Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis-account for most acute bacterial meningitis. Measurement of the effect of protein-polysaccharide conjugate vaccines is most reliable for H influenzae meningitis because one serotype and one age group account

Combination vaccine against invasive meningococcal B and pneumococcal infections: Potential epidemiological and economic impact in the Netherlands

NARCIS (Netherlands)

J.M. Bos; H.C. Rüumke (Hans); K. Welte (Karl); L. Spanjaard (Lodewijk); L. van Alphen (Loek); M.J. Postma (Maarten)

2006-01-01

textabstractBackground: Streptococcus pneumoniae and Neisseria meningitidis group B are among the main causes of invasive bacterial meningitis infections in infants. Worldwide, these diseases lead to significant mortality, morbidity and costs. The societal impact is especially severe since the

Pathophysiology of pneumococcal meningitis

NARCIS (Netherlands)

Geldhoff, M.

2016-01-01

Bacterial meningitis is a serious infectious disease, involving the membranes surrounding the brain and spinal cord, and the subarachnoid space. In the Netherlands most common causative agents are Streptococcus pneumoniae (72%) and Neisseria meningitidis (11%). The incidence of pneumococcal

Next-generation outer membrane vesicle vaccines from concept to clinical trials

NARCIS (Netherlands)

Waterbeemd, van de B.

2013-01-01

Only vaccines containing outer membrane vesicles (OMV) have successfully stopped Neisseria meningitidis serogroup B epidemics. The OMV vaccines, however, provide limited coverage and are difficult to produce. This is caused by an obligatory detergent treatment, which removes lipopolysaccharide

Combination vaccine against invasive meningococcal B and pneumococcal infections - Potential epidemiological and economic impact in The Netherlands

NARCIS (Netherlands)

Bos, J.M.; Rumke, H.C.; Welte, R.; Spanjaard, L.; van Alphen, L.; Postma, M.J.

2006-01-01

Background: Streptococcus pneumoniae and Neisseria meningitidis group B are among the main causes of invasive bacterial meningitis infections in infants. Worldwide, these diseases lead to significant mortality, morbidity and costs. The societal impact is especially severe since the majority of cases

INFEKSI NEISSERIA GONORRHOEAE AKIBAT SEXUAL ABUSE PADA SEORANG ANAK PEREMPUAN

Directory of Open Access Journals (Sweden)

Satya Wydya Yenny

2008-09-01

Full Text Available AbstrakInfeksi Neisseria gonorrhoeae pada anak akibat sexual abuse sangat jarang dilaporkan.Dilaporkan satu kasus infeksi Neisseria gonorrhoeae pada seorang anak perempuan usia 6 tahun setelah mengalami sexual abuse satu minggu yang lalu.Diagnosis ditegakkan berdasarkan anamnesis, pemeriksaan klinis dan pemeriksaan laboratorium. Anamnesis adanya keputihan sejak 5 hari sebelum berobat. Pada pemeriksaan fisis tampak cairan berwarna krem menempel pada celana dalam, cukup banyak, serta sedikit kemerahan dan duh genital pada vulva. Hasil pemeriksaan mikroskopis ditemukan diplokokus Gram negatif dan kultur didapatkan Neisseria gonorrhoeae. Berdasarkan hasil tes sensitivitas, pasien diterapi dengan ceftriaxon 125 mg i.m, dosis tunggal dan memberikan kesembuhan.Infeksi ini membutuhkan penatalaksanaan yang komprehensif karena mempunyai dampak psikologis baik bagi anak maupun keluarga seumur hidupKata kunci : Neisseria gonorrhoeae, sexual abuse, anakAbstractNeisseria gonorrhoe infection in childhood caused by sexual abuse is considered rare reported.A young girl 6 years old suffering gonococcal infection was reported. The diagnostic procedure were base on clinically and laboratory findings. The source of transmission was sexual abuse by an adult man. Physical examination revealed purulent discharge, cream in colour that stains the underwear with minimal vaginal discharge and vulval erythema. Laboratory examination showed Gram-negative diplococcic and isolation of Neisseria gonorrhoeae. This patient had been treated with ceftriaxon 125mg given intramuscularly in a single dose. Result of the treatment was good.The psychological sequelae of sexual abuse and the turmoil in the family produced by suspicions and allegations are largely unknown, but are probably life long.Keywords: Neisseria gonorrhoeae, sexual abuse, childLAPORAN

Combination vaccine against invasive meningococcal B and pneumococcal infections: potential epidemiological and economic impact in the Netherlands

NARCIS (Netherlands)

Bos, Jasper M.; Rümke, Hans C.; Welte, Robert; Spanjaard, Lodewijk; van Alphen, Loek; Postma, Maarten J.

2006-01-01

Streptococcus pneumoniae and Neisseria meningitidis group B are among the main causes of invasive bacterial meningitis infections in infants. Worldwide, these diseases lead to significant mortality, morbidity and costs. The societal impact is especially severe since the majority of cases occur in

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

Phase variation of Opa proteins of Neisseria meningitidis and the effects of bacterial transformation ... Male function for ensuring pollination and reproductive success in Berberis ... Environmental fluctuations do not select for increased variation or ... orthologue of the human ribosomal RNA transcription initiation factor-IA.

Immunological properties of meningococcal lipopolysaccharide from serogroups A, B & C

DEFF Research Database (Denmark)

Jensen, T J; Kharazmi, A; Shand, G

1996-01-01

The aim of the study was to measure and compare the oxidative burst, chemotaxis and cytokine production of human white blood cells, stimulated with meningococcal lipopolysaccharides (LPS) extracted from three different serogroups (A, B and C) of Neisseria meningitidis, and to evaluate whether...

African Journal of Clinical and Experimental Microbiology - Vol 9, No ...

African Journals Online (AJOL)

Sero-epidemiological evaluation of clonal diversity and antimicrobial susceptibility patterns among Neisseria meningitidis isolates from epidemic cases in Jigawa State, Nigeria · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. A Uwah, B Iwalokun, O Badaru, ...

Overcoming the Odds: Long-term psychosocial outcomes in survivors of meningococcal septic shock in childhood, and in their parents

NARCIS (Netherlands)

L.C.A.C. Vermunt (Lindy)

2008-01-01

textabstractSeptic shock, caused by Neisseria meningitidis with petechiae and/or purpura, also called Meningococcal Septic Shock (MSS), is the most serious form of meningococcal infection in early childhood. MSS is a life-threatening illness in mostly previously healthy children, with an unexpected

Enter B and W: two new meningococcal vaccine programmes launched

OpenAIRE

Ladhani, Shamez N; Ramsay, Mary; Borrow, Ray; Riordan, Andrew; Watson, John M; Pollard, Andrew J

2016-01-01

In 2015, the UK became the first country in the world to have a comprehensive routine meningococcal vaccine programme targeting all of the main capsular groups of N. meningitidis. 1 An infant vaccine programme against meningococcal capsular group B Neisseria meningitidis (MenB) was launched from 1st September with an aim to reduce endemic MenB disease in early childhood. On 1st August 2015, an adolescent programme against groups A, C, W and Y meningococci (MenACWY) was rolled out to halt a gr...

Epidemiological evidence for the role of the haemoglobin receptor, HmbR, in meningococcal virulence

OpenAIRE

Harrison, Odile B.; Evans, Nicholas J.; Blair, Jessica M.; Grimes, Holly S.; Tinsley, Colin R.; Nassif, Xavier; Kriz, Paula; Ure, Roisin; Gray, Steve J.; Derrick, Jeremy P.; Maiden, Martin C.J.; Feavers, Ian M.

2009-01-01

The distribution of the haemoglobin receptor gene (hmbR) was investigated in disease and carried Neisseria meningitidis isolates revealing that the gene occurred at a significantly higher frequency in disease isolates compared to those obtained from carriage. Where hmbR was absent, the locus was occupied by the cassettes exl2 or exl3, or with a “pseudo hmbR” gene designated exl4. The hmbR locus in published N. meningitidis genomes, as well as N. gonorrhoeae and N. lactamica ST-640, exhibited ...

Advances with vaccination against Neisseria meningitidis.

Science.gov (United States)

Borrow, Ray

2012-12-01

In the last decade, meningococcal serogroup C conjugate vaccination programs have been demonstrated to be hugely successful with a truly impressive public health impact. In sub-Saharan Africa, with the implementation of an affordable serogroup A conjugate vaccine, it is hoped that a similar public health impact will be demonstrated. Challenges still remain in the quest to develop and implement broadly protective vaccines against serogroup B disease. New, broad coverage vaccines against serogroup B are for the first time becoming available although little is known about their antibody persistence, effectiveness or effect on nasopharyngeal carriage. Enhanced surveillance following any potential vaccine introduction against serogroup B needs to be thoroughly implemented. The future now holds a distinct possibility, globally, for substantially decreasing meningococcal disease, regardless of infecting serogroup. © 2012 Blackwell Publishing Ltd.

Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children

DEFF Research Database (Denmark)

Lundbo, Lene F; Harboe, Zitta Barrella; Clausen, Louise N

2016-01-01

NFKBIA, NFKBIE and NFKBIZ. We aimed to replicate previous findings of genetic variation associated with invasive pneumococcal disease (IPD), and to assess whether similar associations could be found in invasive meningococcal disease (IMD). METHODS: Cases with IPD and IMD and controls were identified......BACKGROUND: Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections. Genetic variation in the immune system may predispose to these infections. Nuclear factor-κB is a key component of the TLR-pathway, controlled by inhibitors, encoded by the genes.......86-1.35). The remaining SNPs were not associated with susceptibility to invasive disease. None of the SNPs were associated with risk of IMD or mortality. CONCLUSIONS: A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis....

Meningococcal adhesion suppresses proapoptotic gene expression and promotes expression of genes supporting early embryonic and cytoprotective signaling of human endothelial cells

Czech Academy of Sciences Publication Activity Database

Linhartová, Irena; Basler, Marek; Ichikawa, J.; Pelicic, V.; Osička, Radim; Lory, S.; Nassif, X.; Šebo, Peter

2006-01-01

Roč. 263, - (2006), s. 109-118 ISSN 0378-1097 R&D Projects: GA ČR GA310/06/0720 Institutional research plan: CEZ:AV0Z50200510 Keywords : neisseria meningitidis * adherence * signaling Subject RIV: EE - Microbiology, Virology Impact factor: 2.068, year: 2006

The molecular origin of the thiamin diphosphate-induced spectral bands of ThDP-dependent enzymes

NARCIS (Netherlands)

Kovina, M.V.; Kok, A.; Sevostyanova, I.A.; Khailova, L.S.; Belkina, N.V.; Kochetov, G.A.

2004-01-01

New and previously published data on a variety of ThDP-dependent enzymes such as baker's yeast transketolase, yeast pyruvate decarboxylase and pyruvate dehydrogenase from pigeon breast muscle, bovine heart, bovine kidney, Neisseria meningitidis and E. coli show their spectral sensitivity to ThDP

African Journal of Biotechnology - Vol 11, No 59 (2012)

African Journals Online (AJOL)

Mutational analysis of fructose-1,6-bisphosphate aldolase of Neisseria meningitidis serogroup B · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Sarfraz A Tunio, Neil J Oldfield, Karl G Wooldridge, David PJ Turner, 12269-12276 ...

Increased proportions of bacteria capable of cleaving IgA1 in the pharynx of infants with atopic disease

DEFF Research Database (Denmark)

Kilian, M; Husby, S; Høst, A

1995-01-01

, and Neisseria meningitidis, of which the first mentioned species was mainly responsible for the difference observed at the 18-mo examination. Percentage proportions of IgA1 protease-producing bacteria were significantly related to passive smoking which may stimulate the premature and more pronounced pharyngeal...

Porin A-specific antibody avidity in patients who are convalescing from meningococcal B disease.

NARCIS (Netherlands)

Vermont, C.L.; Dijken, H.H. van; Groot, R. de; Dobbelsteen, G.P. van den

2005-01-01

Porin A (PorA), which determines the serosubtype of Neisseria meningitidis, is the main antigen of a candidate vaccine against serogroup B meningococci, which has been shown to induce high-avidity antibodies in children. We characterized the immune response of children after convalescing from

The Thioredoxin Domain of Neisseria Gonorrhoeae PilB can use Electrons from DsbD to Reduce Downstream Methionine Sulfoxide Reductases

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Brot,N.; Collet, J.; Johnson, L.; Jonsson, T.; Weissbach, H.; Lowther, W.

2006-01-01

The PilB protein from Neisseria gonorrhoeae is located in the periplasm and made up of three domains. The N-terminal, thioredoxin-like domain (NT domain) is fused to tandem methionine sulfoxide reductase A and B domains (MsrA/B). We show that the {alpha} domain of Escherichia coli DsbD is able to reduce the oxidized NT domain, which suggests that DsbD in Neisseria can transfer electrons from the cytoplasmic thioredoxin to the periplasm for the reduction of the MsrA/B domains. An analysis of the available complete genomes provides further evidence for this proposition in other bacteria where DsbD/CcdA, Trx, MsrA, and MsrB gene homologs are all located in a gene cluster with a common transcriptional direction. An examination of wild-type PilB and a panel of Cys to Ser mutants of the full-length protein and the individually expressed domains have also shown that the NT domain more efficiently reduces the MsrA/B domains when in the polyprotein context. Within this framework there does not appear to be a preference for the NT domain to reduce the proximal MsrA domain over MsrB domain. Finally, we report the 1.6 {angstrom} crystal structure of the NT domain. This structure confirms the presence of a surface loop that makes it different from other membrane-tethered, Trx-like molecules including TlpA, CcmG and ResA. Subtle differences are observed in this loop when compared to the N. meningitidis NT domain structure. The data taken together supports the formation of specific NT domain interactions with the MsrA/B domains and its in vivo recycling partner, DsbD.

Health SA Gesondheid - Vol 9, No 3 (2004)

African Journals Online (AJOL)

The prevalence of side-effects: ciprofloxacin 500 mg single dose prophylaxis against Neisseria meningitidis outbreak in Potchefstroom during July 2003: research · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Michelle Viljoen, Martie S Lubbe, Rina Meyer, 42-54 ...

Crystal structure of an Anti-meningococcal subtype P1.4 PorA antibody provides basis for peptide-vaccine design

NARCIS (Netherlands)

Oomen, Clasien J.; Hoogerhout, Peter; Kuipers, Betsy; Vidarsson, Gestur; van Alphen, Loek; Gros, Piet

2005-01-01

In various western countries, subtype P1.4 of Neisseria meningitidis serogroup B causes the greatest incidence of meningococcal disease. To investigate the molecular recognition of this subtype, we crystallised a peptide (P1HVVVNNKVATH(P11)), corresponding to the subtype P1.4 epitope sequence of

Detection of Neisseria meningitidis in cerebrospinal fluid using a multiplex PCR and the Luminex detection technology

DEFF Research Database (Denmark)

Møller, Jens Kjølseth

2012-01-01

pathogens most frequently found in the cerebrospinal fluid of patients. The Luminex suspension array system uniquely combines flow cytometry, microspheres, laser technology, digital signal processing, and traditional chemistry. In this method, the reaction is carried out in one vessel, in which distinctly...

Phosphoethanolamine Modification of Neisseria gonorrhoeae Lipid A Reduces Autophagy Flux in Macrophages.

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Susu M Zughaier

Full Text Available Autophagy, an ancient homeostasis mechanism for macromolecule degradation, performs an important role in host defense by facilitating pathogen elimination. To counteract this host defense strategy, bacterial pathogens have evolved a variety of mechanisms to avoid or otherwise dysregulate autophagy by phagocytic cells so as to enhance their survival during infection. Neisseria gonorrhoeae is a strictly human pathogen that causes the sexually transmitted infection, gonorrhea. Phosphoethanolamine (PEA addition to the 4' position of the lipid A (PEA-lipid A moiety of the lipooligosaccharide (LOS produced by gonococci performs a critical role in this pathogen's ability to evade innate defenses by conferring decreased susceptibility to cationic antimicrobial (or host-defense peptides, complement-mediated killing by human serum and intraleukocytic killing by human neutrophils compared to strains lacking this PEA decoration. Heretofore, however, it was not known if gonococci can evade autophagy and if so, whether PEA-lipid A contributes to this ability. Accordingly, by using murine macrophages and human macrophage-like phagocytic cell lines we investigated if PEA decoration of gonococcal lipid A modulates autophagy formation. We report that infection with PEA-lipid A-producing gonococci significantly reduced autophagy flux in murine and human macrophages and enhanced gonococcal survival during their association with macrophages compared to a PEA-deficient lipid A mutant. Our results provide further evidence that PEA-lipid A produced by gonococci is a critical component in the ability of this human pathogen to evade host defenses.

An outbreak of meningococcal meningitis in Gauteng, Spring 1996 ...

African Journals Online (AJOL)

Objective. To describe a Neisseri.a meningitidis outbreak in Gauteng during the period 1 July to 31 December 1996. Design. A descriptive study. Setting. Patients with meningococcal meningitis in Gauteng who had been diagnosed by laboratory means, or notified during the period 1 July to 31 December 1996.

Childhood Acute Bacterial Meningitis in Benin City, Nigeria | Ojide ...

African Journals Online (AJOL)

Eleven (47.8%) out of the 23 cases were caused by Streptococcus pneumoniae, 7 (30.4%) Haemophilus influenzae type b, 3 (13.0%) Neisseria meningitidis and 2 (8.7%) for others comprising of Staphylocuccus aureus and Klebssiella pneumoniae. No statistically significant association was established between ABM and ...

Epidemiology and antibiotic resistance of bacterial meningitis in Dapaong, northern Togo

Institute of Scientific and Technical Information of China (English)

Simplice D Karou; Abago Balaka; Mitiname Bamok; Damhan Tchelougou; Malki Assih; Kokou Anani; Kodjo Agbonoko; Jacques Simpore; Comlan de Souza

2012-01-01

Objective:To assess the seasonality of the bacterial meningitis and the antibiotic resistance of incriminated bacteria over the last three years in the northern Togo. Methods: From January 2007 to January 2010, 533 cerebrospinal fluids (CSF) samples were collected from patients suspected of meningitis in the Regional Hospital of Dapaong (northern Togo). After microscopic examination, samples were cultured for bacterial identification and antibiotic susceptibility. Results:The study included 533 patients (306 male and 227 female) aged from 1 day to 55 years [average age (13.00±2.07) years]. Bacterial isolation and identification were attempted for 254/533 (47.65%) samples. The bacterial species identified were:Neisseria meningitidis A (N. meningitidis A) (58.27%), Neisseria meningitidis W135 (N. meningitidis W135) (7.09%), Streptococcus pneumoniae (S. pneumoniae) (26.77%), Haemophilus influenza B (H. influenza B) (6.30%) and Enterobacteriaceae (1.57%). The results indicated that bacterial meningitis occur from November to May with a peak in February for H. influenzae and S. pneumoniae and March for Neisseriaceae. The distribution of positive CSF with regards to the age showed that subjects between 6 and 12 years followed by subjects of 0 to 5 years were most affected with respective frequencies of 67.82% and 56.52% (P20%for both bacterial strains), macrolides (resistance rate> 30%for H. influenzae) quinolones (resistance rate>15%for H. influenzae and N. meningitidis W135). Over three years, the prevalence of S. pneumoniae significantly increased from 8.48%to 73.33%(P<0.001), while the changes in the prevalence of H. influenzae B were not statistically significant: 4.24%, vs. 8.89%, (P= 0.233). Conclusions:Our results indicate that data in African countries differ depending on geographical location in relation to the African meningitis belt. This underlines the importance of epidemiological surveillance of bacterial meningitis.

Uretritis meningocóccica masculina Male meningococcal urethritis

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Federico Díaz González

1994-01-01

Full Text Available

Se presenta el caso de un hombre de 39 años que tuvo uretritis ocho días después de relación orogenital (felatio con una prostituta; de la secreción uretral se aisló Neisseria meningitidis, clasificada como del grupo B; la cepa no producía β lactamasa. El paciente fue tratado con ciprofloxacina y respondió satisfactoriamente; los controles ocho días después de terminar el tratamiento fueron negativos para Neisseria. La inmunofluorescencia para C. trachomatis fue negativa. Se hace una discusión del significado de la N. meningitidis en infecciones genitales.

We report on the case of a 39 year-old white male who developed urethritis eight days after orogenital contact (fellatio with a prostitute. Group B N. meningitidis was recovered from the urethral secretion; the strain was negative for β lactamase production. Response to cyprofloxacin treatment was satisfactory. Control cultures for Neisseriawere negative eight days after completing treatment. At that moment direct immunofluorescence for Chlamydia trachomatis antigens were also negative. The significance of N. meningitidis in genital tract infections is discussed.

Bacterial growth on Mueller Hinton medium sterilized by. gamma. -radiation

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Eisenberg, E. (Israel Atomic Energy Commission, Yavne. Soreq Nuclear Research Center); Bogokowsky, B.; Altmann, G. (Sheba Medical Center, Tel Hashomer (Israel); Tel Aviv Univ. (Israel). Medical School)

1981-12-01

The possibility of radiosterilization of culture media for the cultivation of bacteria was investigated. Mueller Hinton agar, a medium widely used for the propagation of some fastidious pathogenic bacteria, was sterilized with 1.0 and 1.5 Mrad doses of ..gamma..-radiation. Bacteria belonging to seven different species grew as well on the radiosterilized medium as on medium sterilized by heat in a conventional way. Reduction in colony size was observed on the radiosterilized medium with Staphylococcus aureus and Shigella boydii. Neisseria meningitidis, the most fastidious bacterium tested, did not grow at all. The addition of small amounts of catalase corrected the deleterious radiation effect and all bacteria tested could be successfully grown on irradiated Mueller Hinton agar supplemented with up to 11 Keil units catalase per liter medium.

Bacterial growth on Mueller Hinton medium sterilized by γ-radiation

International Nuclear Information System (INIS)

Eisenberg, E.; Bogokowsky, B.; Altmann, G.; Tel Aviv Univ.

1981-01-01

The possibility of radiosterilization of culture media for the cultivation of bacteria was investigated. Mueller Hinton agar, a medium widely used for the propagation of some fastidious pathogenic bacteria, was sterilized with 1.0 and 1.5 Mrad doses of γ-radiation. Bacteria belonging to seven different species grew as well on the radiosterilized medium as on medium sterilized by heat in a conventional way. Reduction in colony size was observed on the radiosterilized medium with Staphylococcus aureus and Shigella boydii. Neisseria meningitidis, the most fastidious bacterium tested, did not grow at all. The addition of small amounts of catalase corrected the deleterious radiation effect and all bacteria tested could be successfully grown on irradiated Mueller Hinton agar supplemented with up to 11 Keil units catalase per liter medium. (author)

Crystal structure of the Neisseria gonorrhoeae MtrD inner membrane multidrug efflux pump.

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Jani Reddy Bolla

Full Text Available Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually-transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. The MtrCDE tripartite multidrug efflux pump, belonging to the hydrophobic and amphiphilic efflux resistance-nodulation-cell division (HAE-RND family, spans both the inner and outer membranes of N. gonorrhoeae and confers resistance to a variety of antibiotics and toxic compounds. We here report the crystal structure of the inner membrane MtrD multidrug efflux pump, which reveals a novel structural feature that is not found in other RND efflux pumps.

1 ORIGINAL ARTICLE

African Journals Online (AJOL)

boaz

ABSTRACT. The aims of this study were to evaluate the impact of conjugate vaccine A, MenAfriVac, on Neisseria meningitidis (Nm) asymptomatic carriage and cerebrospinal meningitis in three health districts (Bogodogo, Kaya, and Dandé) of Burkina Faso. .... Among the fatal cases, 5.569 (65%) were caused by group A N.

Author Details

African Journals Online (AJOL)

Pattern of morbidity and mortality of newborns admitted into the sick and special care baby unit of Enugu State University Teaching Hospital, Enugu state. Abstract PDF · Vol 18, No 1 (2015) - Articles Outbreak of serotype W135 Neisseria meningitidis in central river region of the Gambia between February and June 2012: A ...

The surface-associated elongation factor Tu is concealed for antibody binding on viable pneumococci and meningococci

Czech Academy of Sciences Publication Activity Database

Kolberg, J.; Hammerschmidt, S.; Frank, R.; Jonák, Jiří; Šanderová, Hana; Aase, A.

2008-01-01

Roč. 53, č. 2 (2008), s. 222-230 ISSN 0928-8244 R&D Projects: GA AV ČR KJB500520503 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50200510 Keywords : Streptococcus pneumoniae * Neisseria meningitidis * elongation factor EF-Tu Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.972, year: 2008

Antimicrobial susceptibility pattern of Neisseria gonorrhoeae ...

African Journals Online (AJOL)

The high levels of bacterial resistance against ampicillin, ciprofloxacin, tetracycline, penicillin and spectinomycin, should be taken into account in developing any new guidelines in the management of the infection. Keywords: Neisseria gonorrhoeae, Female infertility Drug Resistance, Ciprofloxacin, Tetracycline, ...

Development of Real-Time PCR Methods for the Detection of Bacterial Meningitis Pathogens without DNA Extraction.

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Jeni Vuong

Full Text Available Neisseria meningitidis (Nm, Haemophilus influenzae (Hi, and Streptococcus pneumoniae (Sp are the lead causes of bacterial meningitis. Detection of these pathogens from clinical specimens using traditional real-time PCR (rt-PCR requires DNA extraction to remove the PCR inhibitors prior to testing, which is time consuming and labor intensive. In this study, five species-specific (Nm-sodC and -ctrA, Hi-hpd#1 and -hpd#3 and Sp-lytA and six serogroup-specific rt-PCR tests (A, B, C, W, X, Y targeting Nm capsular genes were evaluated in the two direct rt-PCR methods using PerfeCTa and 5x Omni that do not require DNA extraction. The sensitivity and specify of the two direct rt-PCR methods were compared to TaqMan traditional rt-PCR, the current standard rt-PCR method for the detection of meningitis pathogens. The LLD for all 11 rt-PCR tests ranged from 6,227 to 272,229 CFU/ml for TaqMan, 1,824-135,982 for 5x Omni, and 168-6,836 CFU/ml for PerfeCTa. The diagnostic sensitivity using TaqMan ranged from 89.2%-99.6%, except for NmB-csb, which was 69.7%. For 5x Omni, the sensitivity varied from 67.1% to 99.8%, with three tests below 90%. The sensitivity of these tests using PerfeCTa varied from 89.4% to 99.8%. The specificity ranges of the 11 tests were 98.0-99.9%, 97.5-99.9%, and 92.9-99.9% for TaqMan, 5x Omni, and PerfeCTa, respectively. PerfeCTa direct rt-PCR demonstrated similar or better sensitivity compared to 5x Omni direct rt-PCR or TaqMan traditional rt-PCR. Since the direct rt-PCR method does not require DNA extraction, it reduces the time and cost for processing CSF specimens, increases testing throughput, decreases the risk of cross-contamination, and conserves precious CSF. The direct rt-PCR method will be beneficial to laboratories with high testing volume.

Meningitis and Meningoencephalitis among Israel Defense Force Soldiers: 20 Years Experience at the Hadassah Medical Centers.

Science.gov (United States)

Pikkel, Yoav Y; Ben-Hur, Tamir; Eliahou, Ruth; Honig, Asaf

2015-11-01

Meningitis and meningoencephalitis pose major risks of morbidity and mortality. To describe 20 years of experience treating infections of the central nervous system in Israel Defense Force (IDF) soldiers, including the common presentations, pathogens and sequelae, and to identify risk groups among soldiers. All soldiers who were admitted to the Hadassah University Medical Center (both campuses: Ein Kerem and Mt. Scopus) due to meningitis and meningoencephalitis from January 1993 to January 2014 were included in this retrospective study. Clinical, laboratory and radiologic data were reviewed from their hospital and army medical corps files. Attention was given to patients' military job description, i.e., combat vs. non-combat soldier, soldiers in training, and medical personnel. We identified 97 cases of suspected meningitis or meningoencephalitis. Six were mistakenly filed and these patients were found to have other disorders. Four soldiers were diagnosed with epidural abscess and five with meningitis due to non-infectious in flammatory diseases. Eighty-two soldiers in active and reserve duty had infectious meningitis or meningoencephalitis. Of these, 46 (56.1%) were combat soldiers and 31 (37.8%) non-combat; 20 (29.2%) were soldiers in training, 10 (12.2%) were training staff and 8 (9.8%) were medical staff. The main pathogens were enteroviruses, Epstein-Barr virus an d Neisseria meningitidis. In our series, soldiers in training, combat soldiers and medical personnel had meningitis and meningoencephalitis more than other soldiers. Enteroviruses are highly infectious pathogens and can cause outbreaks. N. meningitidis among IDF soldiers is still a concern. Early and aggressive treatment with steroids should be considered especially in robust meningoencephalitis cases.

Meningococcal disease, a clinical and epidemiological review.

Science.gov (United States)

Batista, Rodrigo Siqueira; Gomes, Andréia Patrícia; Dutra Gazineo, Jorge Luiz; Balbino Miguel, Paulo Sérgio; Santana, Luiz Alberto; Oliveira, Lisa; Geller, Mauro

2017-11-01

Meningococcal disease is the acute infection caused by Neisseria meningitidis, which has humans as the only natural host. The disease is widespread around the globe and is known for its epidemical potential and high rates of lethality and morbidity. The highest number of cases of the disease is registered in the semi-arid regions of sub-Saharan Africa. In Brazil, it is endemic with occasional outbreaks, epidemics and sporadic cases occurring throughout the year, especially in the winter. The major epidemics of the disease occurred in Brazil in the 70's caused by serogroups A and C. Serogroups B, C and Y represent the majority of cases in Europe, the Americas and Australia. However, there has been a growing increase in serogroup W in some areas. The pathogen transmission happens for respiratory route (droplets) and clinically can lead to meningitis and sepsis (meningococcemia). The treatment is made with antimicrobial and supportive care. For successful prevention, we have some measures like vaccination, chemoprophylaxis and droplets' precautions. In this review, we have described and clarify clinical features of the disease caused by N. meningitidis regarding its relevance for healthcare professionals. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Meningococcal meningitis C in Tamil Nadu, public health perspectives.

Science.gov (United States)

David, Kirubah Vasandhi; Pricilla, Ruby Angeline; Thomas, Beeson

2014-01-01

Meningococcal meningitis has rarely been reported in Tamil Nadu. We report here two children diagnosed with meningococcal meningitis in Vellore, Tamil Nadu, on May 2014. The causative strain was Neisseria meningitidis serotype C. The role of the primary care physician in early diagnosis, appropriate referral, and preventive measures of this disease to the immediate family and community is stressed.

Inflammatory response of Haemophilus influenzae biotype aegyptius causing Brazilian Purpuric Fever

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Gisele Cristiane Gentile Cury

2014-12-01

Full Text Available The Brazilian Purpuric Fever (BPF is a systemic disease with many clinical features of meningococcal sepsis and is usually preceded by purulent conjunctivitis. The illness is caused by Haemophilus influenza biogroup aegyptius, which was associated exclusively with conjunctivitis. In this work construction of the las gene, hypothetically responsible for this virulence, were fusioned with ermAM cassette in Neisseria meningitidis virulent strains and had its DNA transfer to non BPF H. influenzae strains. The effect of the las transfer was capable to increase the cytokines TNFα and IL10 expression in Hec-1B cells line infected with these transformed mutants (in eight log scale of folding change RNA expression. This is the first molecular study involving the las transfer to search an elucidation of the pathogenic factors by horizontal intergeneric transfer from meningococci to H. influenzae.

Results of Multiplex Polymerase Chain Reaction Assay to Identify Urethritis Pathogens

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Mehmet Sarıer

2017-03-01

Full Text Available Objective: The purpose of this study was to evaluate the results of multiplex polymerase chain reaction (PCR test applied to identify the pathogens in male patients who attended our urology clinic with a pre-diagnosis of urethritis related with sexual intercourse. Materials and Methods: In this study, we included a total of 91 male patients, who sought medical advice in our clinic between August 2015 and October 2016 due to complaints of urethral discharge, dysuria and urethral itching, having a visible urethral discharge during the physical examination or a positive leukocyte esterase test (Combur-Test®-Roche in the first urine sample. In the urethral swab samples of these patients, urethritis pathogens were searched with a multiplex PCR test. The multiplex PCR kit, which is able to identify nine pathogens and produced by PathoFinder® (Holland, was used in the process. The pathogens that could be detected by the kit were Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, Gardnerella vaginalis, Trichomonas vaginalis, Treponema pallidum, and Candida albicans. Results: The average age of the subjects was 35.1 (19-57 years. Sixty one out of 91 patients (67% were found to have a pathogen in the urethral swab sample. In 45 patients (49.4%, only one pathogen, in 12 (13.1% - two different pathogens and in 4 (4.3% patients, 3 different pathogens were detected. The pathogens found were as follows: Ureaplasma urealyticum in 22 patients (27.1%, Gardnerella vaginalis in 15 (18.6%, Neisseria gonorrhoeae in 13 (16.1%, Mycoplasma genitalium (10 patients; 12.3%, Mycoplasma hominis (8 patients; 9.9%, Chlamydia trachomatis (8 patients; 9.9%, Trichomonas vaginalis (3 patients; 3.8%, and Candida albicans (2 patients; 2.4%. None of the patients were identified with Treponema pallidum. None of the pathogens were identified in 30 patients (32.9% whose samples were examined by PCR method. Conclusion

Case Report of Urethritis in a Male Patient Infected with Two Different Isolates of Multiple Drug-Resistant Neisseria gonorrhoeae

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Lamiaa Al-Madboly

2017-11-01

Full Text Available We report a brief description of a case suffering from bacterial urethritis, conjunctivitis, and arthritis, caused by two different isolates of multiple drug-resistant Neisseria gonorrhoeae. Initial diagnosis was dependent on the patient history, clinical findings, symptoms, and the bacteriological data. Polymerase chain reaction confirmed the identification of the pathogens. Random amplified polymorphic DNA revealed two different patterns. Susceptibility testing was performed using Kirby–Bauer disk diffusion method and the minimum inhibitory concentration was also determined. It revealed multiple drug resistance associated with β-lactamase production. Only gentamicin, rifampicin, and azithromycin were active against the test pathogens. A dual therapy was initiated using gentamicin as well as azithromycin to treat the possible co-infection with Chlamydia trachomatis. Complete recovery of the patient achieved with resolved symptoms a week later.

Case Report of Urethritis in a Male Patient Infected with Two Different Isolates of Multiple Drug-Resistant Neisseria gonorrhoeae.

Science.gov (United States)

Al-Madboly, Lamiaa; Gheida, Shereen

2017-01-01

We report a brief description of a case suffering from bacterial urethritis, conjunctivitis, and arthritis, caused by two different isolates of multiple drug-resistant Neisseria gonorrhoeae . Initial diagnosis was dependent on the patient history, clinical findings, symptoms, and the bacteriological data. Polymerase chain reaction confirmed the identification of the pathogens. Random amplified polymorphic DNA revealed two different patterns. Susceptibility testing was performed using Kirby-Bauer disk diffusion method and the minimum inhibitory concentration was also determined. It revealed multiple drug resistance associated with β-lactamase production. Only gentamicin, rifampicin, and azithromycin were active against the test pathogens. A dual therapy was initiated using gentamicin as well as azithromycin to treat the possible co-infection with Chlamydia trachomatis . Complete recovery of the patient achieved with resolved symptoms a week later.

Enter B and W: two new meningococcal vaccine programmes launched.

Science.gov (United States)

Ladhani, Shamez N; Ramsay, Mary; Borrow, Ray; Riordan, Andrew; Watson, John M; Pollard, Andrew J

2016-01-01

In 2015, the UK became the first country in the world to have a comprehensive routine meningococcal vaccine programme targeting all of the main capsular groups of N. meningitidis. 1 An infant vaccine programme against meningococcal capsular group B Neisseria meningitidis (MenB) was launched from 1st September with an aim to reduce endemic MenB disease in early childhood. On 1st August 2015, an adolescent programme against groups A, C, W and Y meningococci (MenACWY) was rolled out to halt a growing outbreak of capsular group W disease (MenW) caused by a hypervirulent clone of N. meningitidis, in addition to maintaining control against MenC disease provided by the current adolescent programme. 2. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Etiologic agents of central nervous system infections among febrile hospitalized patients in the country of Georgia.

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Tamar Akhvlediani

Full Text Available OBJECTIVES: There is a large spectrum of viral, bacterial, fungal, and prion pathogens that cause central nervous system (CNS infections. As such, identification of the etiological agent requires multiple laboratory tests and accurate diagnosis requires clinical and epidemiological information. This hospital-based study aimed to determine the main causes of acute meningitis and encephalitis and enhance laboratory capacity for CNS infection diagnosis. METHODS: Children and adults patients clinically diagnosed with meningitis or encephalitis were enrolled at four reference health centers. Cerebrospinal fluid (CSF was collected for bacterial culture, and in-house and multiplex RT-PCR testing was conducted for herpes simplex virus (HSV types 1 and 2, mumps virus, enterovirus, varicella zoster virus (VZV, Streptococcus pneumoniae, HiB and Neisseria meningitidis. RESULTS: Out of 140 enrolled patients, the mean age was 23.9 years, and 58% were children. Bacterial or viral etiologies were determined in 51% of patients. Five Streptococcus pneumoniae cultures were isolated from CSF. Based on in-house PCR analysis, 25 patients were positive for S. pneumoniae, 6 for N. meningitidis, and 1 for H. influenzae. Viral multiplex PCR identified infections with enterovirus (n = 26, VZV (n = 4, and HSV-1 (n = 2. No patient was positive for mumps or HSV-2. CONCLUSIONS: Study findings indicate that S. pneumoniae and enteroviruses are the main etiologies in this patient cohort. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve health outcomes of CNS infection cases in Georgia.

Etiologic Agents of Central Nervous System Infections among Febrile Hospitalized Patients in the Country of Georgia

Science.gov (United States)

Akhvlediani, Tamar; Bautista, Christian T.; Shakarishvili, Roman; Tsertsvadze, Tengiz; Imnadze, Paata; Tatishvili, Nana; Davitashvili, Tamar; Samkharadze, Tamar; Chlikadze, Rusudan; Dvali, Natia; Dzigua, Lela; Karchava, Mariam; Gatserelia, Lana; Macharashvili, Nino; Kvirkvelia, Nana; Habashy, Engy Emil; Farrell, Margaret; Rowlinson, Emily; Sejvar, James; Hepburn, Matthew; Pimentel, Guillermo; Dueger, Erica; House, Brent; Rivard, Robert

2014-01-01

Objectives There is a large spectrum of viral, bacterial, fungal, and prion pathogens that cause central nervous system (CNS) infections. As such, identification of the etiological agent requires multiple laboratory tests and accurate diagnosis requires clinical and epidemiological information. This hospital-based study aimed to determine the main causes of acute meningitis and encephalitis and enhance laboratory capacity for CNS infection diagnosis. Methods Children and adults patients clinically diagnosed with meningitis or encephalitis were enrolled at four reference health centers. Cerebrospinal fluid (CSF) was collected for bacterial culture, and in-house and multiplex RT-PCR testing was conducted for herpes simplex virus (HSV) types 1 and 2, mumps virus, enterovirus, varicella zoster virus (VZV), Streptococcus pneumoniae, HiB and Neisseria meningitidis. Results Out of 140 enrolled patients, the mean age was 23.9 years, and 58% were children. Bacterial or viral etiologies were determined in 51% of patients. Five Streptococcus pneumoniae cultures were isolated from CSF. Based on in-house PCR analysis, 25 patients were positive for S. pneumoniae, 6 for N. meningitidis, and 1 for H. influenzae. Viral multiplex PCR identified infections with enterovirus (n = 26), VZV (n = 4), and HSV-1 (n = 2). No patient was positive for mumps or HSV-2. Conclusions Study findings indicate that S. pneumoniae and enteroviruses are the main etiologies in this patient cohort. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve health outcomes of CNS infection cases in Georgia. PMID:25369023

Urethritis-associated Pathogens in Urine from Men with Non-gonococcal Urethritis: A Case-control Study.

Science.gov (United States)

Frølund, Maria; Lidbrink, Peter; Wikström, Arne; Cowan, Susan; Ahrens, Peter; Jensen, Jørgen Skov

2016-06-15

The aetiology of non-gonococcal urethritis (NGU) remains unexplained in 30-40% of patients. Urine samples from men attending Swedish sexually transmitted disease clinics were examined by species-specific quantitative PCRs for Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, Ureaplasma urealyticum, U. parvum, adenovirus, herpes simplex virus, Neisseria meningitidis, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae. A total of 187 men with acute NGU (symptoms ≤ 30 days) and 24 with chronic NGU (symptoms < 30 days) were cases, and 73 men without NGU were controls. Number of lifetime sexual partners was negatively associated with U. urealyticum bacterial load. C. trachomatis and M. genitalium were associated with NGU, as was U. urealyticum, with bacterial loads ≥ 1.3 × 103 genome equivalents/ml urine. Virus and H. influenzae might explain a few NGU cases, but the aetiology in at least 24% of patients with acute NGU was unexplained. In multivariate analysis, detection of U. urealyticum was significantly more common in acute NGU (20%) compared with controls (11%).

Profil des méningites bactériennes pédiatriques au Centre ...

African Journals Online (AJOL)

Les germes identifiés étaient Haemophilus influenzae b (40%), Streptococcus pneumoniae (37,1%), Neisseria meningitidis (20%) et Cryptocoque (2,9%). Le taux de létalité était de 33,3%. Conclusion : cette étude a confirmé la gravité des méningites bactériennes pédiatriques et rappel ainsi, l'importance de la vaccination.

Invasive meningococcal disease without meningitis: a forgotten diagnosis

Directory of Open Access Journals (Sweden)

Walayat S

2018-04-01

Full Text Available Saqib Walayat,1 Nooreen Hussain,1 Abdullah H Malik,1 Elsa Vazquez-Melendez,1 Bhagat S Aulakh,2 Teresa Lynch1 1Department of Internal Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL, USA; 2Department of Pulmonary/Critical Care Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL, USA Abstract: Neisseria meningitidis, a Gram-negative diplococcus, is an uncommon cause of pneumonia. There have been only about 344 cases reported worldwide from 1906 to 2015. To our knowledge, there have been only 3 cases reported in the USA in the past 2 decades. We present a case of a 72-year-old male with a past medical history of severe COPD, obstructive sleep apnea, and stage I lung cancer status post-stereotactic body radiation therapy 1 year ago, who was admitted with a 6-day history of productive cough with yellowish sputum, shortness of breath, extreme myalgias, and fatigue. Chest X-ray revealed an infiltrative process in the left lower lung field and left-sided pleural effusion. Blood cultures grew beta-lactamase-negative N. meningitidis after 24 hours. Our patient was initially treated with broad-spectrum antibiotics, which were later switched to amoxicillin to complete a total of 14 days of antibiotics. Diagnosing meningococcal pneumonia requires a high level of suspicion, as sputum cultures may be falsely positive due to asymptomatic carriage of the organism in the upper respiratory tract in up to 10% of outpatient population. We highlight this case as early recognition and treatment is critical. The case fatality rate for N. meningitidis pneumonia has been reported to be higher compared with meningococcal meningitis. Keywords: Neisseria meningitidis, pneumonia, invasive meningococcal pneumonia, sepsis

Diagnosis of Neisseria gonorrhoeae Using Molecular Beacon

Science.gov (United States)

Patel, Achchhe Lal; Sonkar, Subash Chandra; Kumari, Indu; Saluja, Daman

2015-01-01

Neisseria gonorrhoeae is an important sexually transmitted diseases (STD) causing pathogen worldwide. Due to absence of an affordable diagnostic assay, routine screening of gonococcal infection becomes impossible in developing countries where infection rates are maximum. Treatment is given on the basis of symptoms alone which leads to spread of infection. Thus, development of a rapid, sensitive, specific, and PCR based visual diagnostic assay suitable for developing countries, required for better disease management, is aimed at in present study. Endocervical swabs were collected from patients visiting gynecology department of various hospitals in Delhi. In-house PCR based assay was developed and modified to visual assay using molecular beacon for end-point detection. It was evaluated against Roche AMPLICOR NG kit and rmp gene. Specificity of beacon was confirmed by competition experiments. Diagnostic test was 98.21% specific and 99.59% sensitive whereas negative and positive predicted value were 99.40% and 98.78%, respectively. We also observed that twice the concentration (2X) of premix was stable at 4°C for 4 months and dry swab samples gave concordant results with that of wet swabs. These features make the test best suitable for routine diagnosis of genital infections in developing countries. PMID:25802857

Polysaccharide production in batch process of Neisseria meningitidis serogroup C comparing Frantz, modified Frantz and Cartlin 6 cultivation media Produção de polissacarídeo em processo de cultivo descontínuo de Neisseria meningitidis sorogrupo C comparando os meios de cultivo Frantz, Frantz modificado e Catlin 6

Directory of Open Access Journals (Sweden)

Marcelo Fossa da Paz

2003-04-01

Full Text Available Polysaccharide of N. meningitidis serogroup C constitutes the antigen for the vaccine against meningitis. The goal of this work was to compare three cultivation media for production of this polysaccharide: Frantz, modified Frantz medium (with replacement of glucose by glycerol, and Catlin 6 (a synthetic medium with glucose. The comparative criteria were based on the final polysaccharide concentrations and the yield coefficient cell/polysaccharide (Y P/X. The kinetic parameters: pH, substrate consumption and cell growth were also determined. For this purpose, 9 cultivation runs were carried out in a 80 L New Brunswick bioreactor, under the following conditions: 42 L of culture medium, temperature 35ºC, air flow 5 L/min, agitation frequency 120 rpm and vessel pressure 6 psi, without dissolved oxygen or pH controls. The cultivation runs were divided in three groups, with 3 repetitions each. The cultivation using the Frantz medium presented the best results: average of final polysaccharide concentration = 0.134 g/L and Y P/X=0.121, followed by Catlin 6 medium, with results of 0.095 g/L and 0.067 respectively. Considering the principal advantages in the use of the synthetic medium, i.e. facilitation of a cultivation and purification steps of the polysaccharide production process, there is a possibility that in the near future, Catlin 6 will replace the traditional Frantz medium.O polissacarídeo de N. meningitidis sorogrupo C constitui o antígeno para a elaboração da vacina contra a meningite C. O objetivo deste trabalho foi comparar três meios de cultivo para produção desse polissacarídeo: Frantz, Frantz modificado (com a substituição de glicose por glicerol e Catlin 6 (meio sintético com glicose. Os critérios comparativos foram baseados nas concentrações finais de polissacarídeo e o fator de conversão célula/polissacarídeo (Y P/X. Também foram determinados os parâmetros cinéticos de pH, consumo de substrato e crescimento

Arginine- and Polyamine-Induced Lactic Acid Resistance in Neisseria gonorrhoeae.

Directory of Open Access Journals (Sweden)

Zheng Gong

Full Text Available Microbe-derived lactic acid protects women from pathogens in their genital tract. The purpose of this study was to determine lactic acid susceptibility of Neisseria gonorrhoeae, and identify potential acid resistance mechanisms present in this pathogen. Tested in vitro, lactic acid killed all 10 gonococcal strains analyzed in a low pH-dependent manner. Full inactivation occurred at pH 4.5. At low pH, lactic acid treatment resulted in the entry of the DNA-binding fluorochrome propidium iodide into the microbial cells, suggesting that hydrogen ions from lactic acid compromise the integrity of the bacterial cell wall/membrane. Most likely, hydrogen ions also inactivate intracellular proteins since arginine rendered significant protection against lactic acid presumably through action of the gonococcal arginine decarboxylase, an enzyme located in the bacterial cytoplasm. Surprisingly, arginine also lessened lactic acid-mediated cell wall/membrane disruption. This effect is probably mediated by agmatine, a triamine product of arginine decarboxylase, since agmatine demonstrated a stronger protective effect on GC than arginine at equal molar concentration. In addition to agmatine, diamines cadaverine and putrescine, which are generated by bacterial vaginosis-associated microbes, also induced significant resistance to lactic acid-mediated GC killing and cell wall/membrane disruption. These findings suggest that the arginine-rich semen protects gonococci through both neutralization-dependent and independent mechanisms, whereas polyamine-induced acid resistance contributes to the increased risk of gonorrhea in women with bacterial vaginosis.

Identification of new meningococcal serogroup B surface antigens through a systematic analysis of neisserial genomes.

Science.gov (United States)

Pajon, Rolando; Yero, Daniel; Niebla, Olivia; Climent, Yanet; Sardiñas, Gretel; García, Darién; Perera, Yasser; Llanes, Alejandro; Delgado, Maité; Cobas, Karem; Caballero, Evelin; Taylor, Stephen; Brookes, Charlotte; Gorringe, Andrew

2009-12-11

The difficulty of inducing an effective immune response against the Neisseria meningitidis serogroup B capsular polysaccharide has lead to the search for vaccines for this serogroup based on outer membrane proteins. The availability of the first meningococcal genome (MC58 strain) allowed the expansion of high-throughput methods to explore the protein profile displayed by N. meningitidis. By combining a pan-genome analysis with an extensive experimental validation to identify new potential vaccine candidates, genes coding for antigens likely to be exposed on the surface of the meningococcus were selected after a multistep comparative analysis of entire Neisseria genomes. Eleven novel putative ORF annotations were reported for serogroup B strain MC58. Furthermore, a total of 20 new predicted potential pan-neisserial vaccine candidates were produced as recombinant proteins and evaluated using immunological assays. Potential vaccine candidate coding genes were PCR-amplified from a panel of representative strains and their variability analyzed using maximum likelihood approaches for detecting positive selection. Finally, five proteins all capable of inducing a functional antibody response vs N. meningitidis strain CU385 were identified as new attractive vaccine candidates: NMB0606 a potential YajC orthologue, NMB0928 the neisserial NlpB (BamC), NMB0873 a LolB orthologue, NMB1163 a protein belonging to a curli-like assembly machinery, and NMB0938 (a neisserial specific antigen) with evidence of positive selection appreciated for NMB0928. The new set of vaccine candidates and the novel proposed functions will open a new wave of research in the search for the elusive neisserial vaccine.

Desarrollo de un método de CLAR-IR para la determinación de etanol residual en vacuna Development of a HPLC-IR method for determination of residual ethanol in vaccine

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Matilde Cuevas Valdespino

2009-08-01

Full Text Available Los ingredientes farmacéuticos activos de la vacuna antimeningocócica cubana VA-MENGOC-BC TM (vesículas de membrana externa purificadas de Neisseria meningitidis, serogrupo B y polisacárido capsular purificado de Neisseria meningitidis, serogrupo C son conservados en etanol, de ahí que dicha vacuna posea un contenido de etanol residual, cuya concentración real no se conocía hasta el momento. Las regulaciones internacionales plantean que los productos biofarmacéuticos y sus ingredientes farmacéuticos activos deben tener bien caracterizadas todas sus impurezas, por lo que el objetivo de este trabajo fue el desarrollo de un método de determinación de etanol mediante cromatografía líquida de alta resolución-índice de refracción para estos fines y su comparación con un método utilizado frecuentemente para cuantificar este solvente, como es la cromatografía gaseosa. El método evaluado resultó ser útil y con una buena robustez para la determinación de este solvente orgánico en esta vacuna antimenigocócica. No se detectaron diferencias estadísticamente significativas entre los resultados obtenidos al evaluar las mismas muestras de vacuna mediante ambos métodos cromatográficos (cromatografía líquida de alta resolución y cromatografía gaseosa, lo que indica la posibilidad del uso de la cromatografía líquida de alta resolución en sustitución de la cromatografía gaseosa para esta determinación.Active pharmaceutical ingredients of Cuban anti-meningococcal vaccine VA-MENGOC-BC TM (vesicles of purified external membranes of Neisseria meningitidis, B serum-group, and purified capsular polysaccharide of Neisseria meningitidis, serum-group C are stored in ethanol, thus that such vaccine has residual ethanol content, of which real concentration is not known just now. International regulations propose that the biopharmaceutical products and its active pharmaceutical ingredients must to have well defined all impurities, thus

CEACAM3: ein neuartiger phagozytischer Rezeptor der angeborenen Immunantwort zur Erkennung human-spezifischer Pathogene

OpenAIRE

Schmitter, Tim

2006-01-01

Eine Infektion durch das ausschließlich human-spezifische Pathogen Neisseria gonorrhoeae manifestiert sich bei einer symptomatischen Kolonisierung in der sog. Gonorrhö, einer venerischen Erkrankung, die durch akute Inflammation des befallenen Gewebes und durch die massive Infiltration von Granulozyten charakterisiert ist. Die Gonokokken können im Verlauf einer symptomatischen Infektion über ihre OpaCEA-Adhäsine mit CEACAM Proteinen unterschiedlicher Wirtszellen interagieren. In der vorliegend...

Algunas consideraciones sobre Neisseria gonorrhoeae

OpenAIRE

Pardi, Germán; Pérez, María Fernanda; Pacheco, Aura; Mata de Henning, Magdalena

2004-01-01

En el presente artículo, se describen los principales aspectos relacionados con Neisseria gonorrhoeae, microorganismo que se puede encontrar presente como parte de la microbiota transitoria o transeúnte de la cavidad bucal de algunos individuos, donde se destacan: Historia, taxonomía, características morfológicas, fisiológicas y de cultivo, ultraestructura, estructura antigénica, así como algunas consideraciones en referencia a la ecología y a los mecanismos de patogenicidad por parte de esta...

Properdin deficiency associated with recurrent otitis media and pneumonia, and identification of male carrier with Klinefelter syndrome

DEFF Research Database (Denmark)

Schejbel, Lone; Rosenfeldt, Vibeke; Marquart, Hanne

2009-01-01

Properdin is an initiator and stabilizer of the alternative complement activation pathway (AP). Deficiency of properdin is a rare X-linked condition characterized by increased susceptibility to infection with Neisseria meningitidis associated with a high mortality rate. We report properdin defici...... otitis media (P=0.0012), as well as recurrent pneumonia (P=0.0017). This study is the first to show a significant association between properdin deficiency and recurrent infections....

Probing the Ca2+-assisted pi-pi interaction during Ca2+-dependent protein folding

Czech Academy of Sciences Publication Activity Database

Matyska Lišková, Petra; Fišer, Radovan; Macek, Pavel; Chmelík, Josef; Sýkora, Jan; Bednárová, Lucie; Konopásek, I.; Bumba, Ladislav

2016-01-01

Roč. 12, č. 2 (2016), s. 531-541 ISSN 1744-683X R&D Projects: GA ČR(CZ) GAP207/11/0717; GA ČR(CZ) GBP208/12/G016; GA MŠk LO1509 Institutional support: RVO:61388971 ; RVO:61388963 ; RVO:61388955 Keywords : METAL-ION-BINDING * NEISSERIA-MENINGITIDIS * RTX PROTEINS Subject RIV: CE - Biochemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 3.889, year: 2016

A gonococcal homologue of meningococcal γ-glutamyl transpeptidase gene is a new type of bacterial pseudogene that is transcriptionally active but phenotypically silent

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Watanabe Haruo

2005-10-01

Full Text Available Abstract Background It has been speculated that the γ-glutamyl transpeptidase (ggt gene is present only in Neisseria meningitidis and not among related species such as Neisseria gonorrhoeae and Neisseria lactamica, because N. meningitidis is the only bacterium with GGT activity. However, nucleotide sequences highly homologous to the meningococcal ggt gene were found in the genomes of N. gonorrhoeae isolates. Results The gonococcal homologue (ggt gonococcal homologue; ggh was analyzed. The nucleotide sequence of the ggh gene was approximately 95 % identical to that of the meningococcal ggt gene. An open reading frame in the ggh gene was disrupted by an ochre mutation and frameshift mutations induced by a 7-base deletion, but the amino acid sequences deduced from the artificially corrected ggh nucleotide sequences were approximately 97 % identical to that of the meningococcal ggt gene. The analyses of the sequences flanking the ggt and ggh genes revealed that both genes were localized in a common DNA region containing the fbp-ggt (or ggh-glyA-opcA-dedA-abcZ gene cluster. The expression of the ggh RNA could be detected by dot blot, RT-PCR and primer extension analyses. Moreover, the truncated form of ggh-translational product was also found in some of the gonococcal isolates. Conclusion This study has shown that the gonococcal ggh gene is a pseudogene of the meningococcal ggt gene, which can also be designated as Ψggt. The gonococcal ggh (Ψggt gene is the first identified bacterial pseudogene that is transcriptionally active but phenotypically silent.

Periodontal-disease-associated biofilm: A reservoir for pathogens of medical importance.

Science.gov (United States)

Vieira Colombo, Ana Paula; Magalhães, Clarissa Bichara; Hartenbach, Fátima Aparecida Rocha Resende; Martins do Souto, Renata; Maciel da Silva-Boghossian, Carina

2016-05-01

The ecological diversity of the periodontal microenvironment may provide suitable conditions for the colonization of species not usually considered members of the oral microbiota. In this investigation, we aimed to determine the prevalence and levels of pathogenic species of medical relevance in the microbiota of individuals with distinct periodontal clinical status. Subgingival biofilm was obtained from patients with periodontal health (H, n = 81), gingivitis (G, n = 55), generalized aggressive (AgP, n = 36) or chronic periodontitis (CP, n = 98), and analyzed for 39 microbial taxa using a checkerboard DNA-DNA hybridization technique. Microbial differences among groups, as well as associations between clinical and microbiological parameters were sought by non-parametric and univariate correlation tests. Neisseria spp., Peptostreptococus anaerobius, Candida albicans, enterobacteria, Pseudomonas aeruginosa, Eubacterium saphenum, Clostridium difficile and Olsenella uli were detected in high mean prevalence and counts in the subgingival microbiota of the study population. Species that were more related to periodontal inflammation and tissue destruction at the patient and site levels included enterobacteria, C. albicans, Neisseria spp., P. aeruginosa, O. uli, Hafnia alvei, Serratia marcescens and Filifactor alocis (p < 0.05). In contrast, Fusobacterium necrophorum, Lactobacillus acidophilus, Staphylococcus aureus and Streptococcus pneumoniae were associated with periodontal health (p < 0.05). Pathogenic species of medical importance may be detected in high prevalence and levels in the periodontal microbiota. Regardless of their role in periodontal health or disease, the periodontal biofilm may be a source for dissemination and development of systemic infections by these pathogenic microorganisms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Infection of Human Fallopian Tube Epithelial Cells with Neisseria gonorrhoeae Protects Cells from Tumor Necrosis Factor Alpha-Induced Apoptosis

Science.gov (United States)

Morales, Priscilla; Reyes, Paz; Vargas, Macarena; Rios, Miguel; Imarai, Mónica; Cardenas, Hugo; Croxatto, Horacio; Orihuela, Pedro; Vargas, Renato; Fuhrer, Juan; Heckels, John E.; Christodoulides, Myron; Velasquez, Luis

2006-01-01

Following infection with Neisseria gonorrhoeae, bacteria may ascend into the Fallopian tubes (FT) and induce salpingitis, a major cause of infertility. In the FT, interactions between mucosal epithelial cells and gonococci are pivotal events in the pathogen's infection cycle and the inflammatory response. In the current study, primary FT epithelial cells were infected in vitro with different multiplicities of infection (MOI) of Pil+ Opa+ gonococci. Bacteria showed a dose-dependent association with cells and induced the secretion of tumor necrosis factor alpha (TNF-α). A significant finding was that gonococcal infection (MOI = 1) induced apoptosis in approximately 30% of cells, whereas increasing numbers of bacteria (MOI = 10 to 100) did not induce apoptosis. Apoptosis was observed in only 11% of cells with associated bacteria, whereas >84% of cells with no adherent bacteria were apoptotic. TNF-α was a key contributor to apoptosis, since (i) culture supernatants from cells infected with gonococci (MOI = 1) induced apoptosis in naïve cultures, suggesting that a soluble factor was responsible; (ii) gonococcal infection-induced apoptosis was inhibited with anti-TNF-α antibodies; and (iii) the addition of exogenous TNF-α induced apoptosis, which was inhibited by the presence of increasing numbers of bacteria (MOI = 10 to 100). These data suggest that TNF-α-mediated apoptosis of FT epithelial cells is likely a primary host defense mechanism to prevent pathogen colonization. However, epithelial cell-associated gonococci have evolved a mechanism to protect the cells from undergoing TNF-α-mediated apoptosis, and this modulation of the host innate response may contribute to establishment of infection. Understanding the antiapoptotic mechanisms used by Neisseria gonorrhoeae will inform the pathogenesis of salpingitis and could suggest new intervention strategies for prevention and treatment of the disease. PMID:16714596

Deciphering the contribution of human meningothelial cells to the inflammatory and antimicrobial response at the meninges.

Science.gov (United States)

Royer, Pierre-Joseph; Rogers, Andrew J; Wooldridge, Karl G; Tighe, Patrick; Mahdavi, Jafar; Rittig, Michael G; Ala'Aldeen, Dlawer

2013-11-01

We have investigated the response of primary human meningothelial cells to Neisseria meningitidis. Through a transcriptome analysis, we provide a comprehensive examination of the response of meningothelial cells to bacterial infection. A wide range of chemokines are elicited which act to attract and activate the main players of innate and adaptive immunity. We showed that meningothelial cells expressed a high level of Toll-like receptor 4 (TLR4), and, using a gene silencing strategy, we demonstrated the contribution of this pathogen recognition receptor in meningothelial cell activation. Secretion of interleukin-6 (IL-6), CXCL10, and CCL5 was almost exclusively TLR4 dependent and relied on MyD88 and TRIF adaptor cooperation. In contrast, IL-8 induction was independent of the presence of TLR4, MyD88, and TRIF. Transcription factors NF-κB p65, p38 mitogen-activated protein kinase (MAPK), Jun N-terminal protein kinase (JNK1), IRF3, and IRF7 were activated after contact with bacteria. Interestingly, the protein kinase IRAK4 was found to play a minor role in the meningothelial cell response to Neisseria infection. Our work highlights the role of meningothelial cells in the development of an immune response and inflammation in the central nervous system (CNS) in response to meningococcal infection. It also sheds light on the complexity of intracellular signaling after TLR triggering.

21 CFR 866.3390 - Neisseria spp. direct serological test reagents.

Science.gov (United States)

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3390... Neisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused...

Expanding the potential of NAI-107 for treating serious ESKAPE pathogens

DEFF Research Database (Denmark)

Brunati, Cristina; Thomsen, Thomas T; Gaspari, Eleonora

2018-01-01

Objectives: To characterize NAI-107 and related lantibiotics for their in vitro activity against Gram-negative pathogens, alone or in combination with polymyxin, and against non-dividing cells or biofilms of Staphylococcus aureus. NAI-107 was also evaluated for its propensity to select or induce...... showed that NAI-107 and its brominated variant are highly active against Neisseria gonorrhoeae and some other fastidious Gram-negative pathogens. Furthermore, all compounds strongly synergized with polymyxin against Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas...... self-resistance in Gram-positive bacteria. Methods: We used MIC determinations and chequerboard experiments to establish the antibacterial activity of the examined compounds against target microorganisms. Time-kill assays were used to evaluate killing of exponential and stationary-phase cells...

Protein carriers of conjugate vaccines: characteristics, development, and clinical trials.

Science.gov (United States)

Pichichero, Michael E

2013-12-01

The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products.

Protein carriers of conjugate vaccines

Science.gov (United States)

Pichichero, Michael E

2013-01-01

The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

The Phosphocarrier Protein HPr Contributes to Meningococcal Survival during Infection.

Directory of Open Access Journals (Sweden)

Ana Antunes

Full Text Available Neisseria meningitidis is an exclusively human pathogen frequently carried asymptomatically in the nasopharynx but it can also provoke invasive infections such as meningitis and septicemia. N. meningitidis uses a limited range of carbon sources during infection, such as glucose, that is usually transported into bacteria via the phosphoenolpyruvate (PEP:sugar phosphotransferase system (PTS, in which the phosphocarrier protein HPr (encoded by the ptsH gene plays a central role. Although N. meningitidis possesses an incomplete PTS, HPr was found to be required for its virulence. We explored the role of HPr using bioluminescent wild-type and ΔptsH strains in experimental infection in transgenic mice expressing the human transferrin. The wild-type MC58 strain was recovered at higher levels from the peritoneal cavity and particularly from blood compared to the ΔptsH strain. The ΔptsH strain provoked lower levels of septicemia in mice and was more susceptible to complement-mediated killing than the wild-type strain. We tested whether meningococcal structures impacted complement resistance and observed that only the capsule level was decreased in the ΔptsH mutant. We therefore compared the transcriptomic profiles of wild-type and ΔptsH strains and identified 49 differentially expressed genes. The HPr regulon contains mainly hypothetical proteins (43% and several membrane-associated proteins that could play a role during host interaction. Some other genes of the HPr regulon are involved in stress response. Indeed, the ΔptsH strain showed increased susceptibility to environmental stress conditions. Our data suggest that HPr plays a pleiotropic role in host-bacteria interactions most likely through the innate immune response that may be responsible for the enhanced clearance of the ΔptsH strain from blood.

Quality by design approach in the development of an ultra-high-performance liquid chromatography method for Bexsero meningococcal group B vaccine.

Science.gov (United States)

Nompari, Luca; Orlandini, Serena; Pasquini, Benedetta; Campa, Cristiana; Rovini, Michele; Del Bubba, Massimo; Furlanetto, Sandra

2018-02-01

Bexsero is the first approved vaccine for active immunization of individuals from 2 months of age and older to prevent invasive disease caused by Neisseria meningitidis serogroup B. The active components of the vaccine are Neisseria Heparin Binding Antigen, factor H binding protein, Neisseria adhesin A, produced in Escherichia coli cells by recombinant DNA technology, and Outer Membrane Vesicles (expressing Porin A and Porin B), produced by fermentation of Neisseria meningitidis strain NZ98/254. All the Bexsero active components are adsorbed on aluminum hydroxide and the unadsorbed antigens content is a product critical quality attribute. In this paper the development of a fast, selective and sensitive ultra-high-performance liquid chromatography (UHPLC) method for the determination of the Bexsero antigens in the vaccine supernatant is presented. For the first time in the literature, the Quality by Design (QbD) principles were applied to the development of an analytical method aimed to the quality control of a vaccine product. The UHPLC method was fully developed within the QbD framework, the new paradigm of quality outlined in International Conference on Harmonisation guidelines. Critical method attributes (CMAs) were identified with the capacity factor of Neisseria Heparin Binding Antigen, antigens resolution and peak areas. After a scouting phase, aimed at selecting a suitable and fast UHPLC operative mode for the vaccine antigens separation, risk assessment tools were employed to define the critical method parameters to be considered in the screening phase. Screening designs were applied for investigating at first the effects of vial type and sample concentration, and then the effects of injection volume, column type, organic phase starting concentration, ramp time and temperature. Response Surface Methodology pointed out the presence of several significant interaction effects, and with the support of Monte-Carlo simulations led to map out the design space, at

Molecular bacterial diversity and bioburden of commercial airliner cabin air

Energy Technology Data Exchange (ETDEWEB)

La Duc, M.T.; Stuecker, T.; Venkateswaran, K. [California Inst. of Technology, Pasadena, CA (United States). Jet Propulsion Laboratory, Biotechnology and Planetary Protection Group

2007-11-15

Microorganisms that exist in aircraft air systems are considered to be the primary source of microbial contamination that can lead to illness shortly after flying. More than 600 million passengers board commercial airline flights annually in the United States alone. In this study, culture-independent, biomarker-targeted bacterial enumeration and identification strategies were used to estimate total bacterial burden and diversity within the cabin air of commercial airliners. Air-impingement was used to collect samples of microorganisms from 4 flights on 2 commercial carriers. The total viable microbial population ranged from below detection limits to 4.1 x 10{sup 6} cells/m{sup 3} of air. Microbes were found to gradually accumulate from the time of passenger boarding through mid-flight. A sharp decline in bacterial abundance was then observed. Representatives of the {alpha}, {beta} and {gamma} Proteobacteria, as well as Gram-positive bacteria, were isolated in varying abundance. Airline A had large abundances of Neisseria meningitidis rRNA gene sequences and Streptococcus oralis/mitis sequences. Airline B was dominated by pseudomonas synxantha sequences as well as N. meningitidis and S. oralis/mitis. The cabin air samples housed low bacterial diversity and were typically dominated by a particular subset of bacteria, notably opportunistic pathogenic inhabitants of the human respiratory tract and oral cavity. The microbes were found largely around the ventilation ducts and gasper conduits that supply cabin air. 45 refs., 4 tabs., 3 figs.

Is the C-terminal insertional signal in Gram-negative bacterial outer membrane proteins species-specific or not?

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Paramasivam Nagarajan

2012-09-01

Full Text Available Abstract Background In Gram-negative bacteria, the outer membrane is composed of an asymmetric lipid bilayer of phopspholipids and lipopolysaccharides, and the transmembrane proteins that reside in this membrane are almost exclusively β-barrel proteins. These proteins are inserted into the membrane by a highly conserved and essential machinery, the BAM complex. It recognizes its substrates, unfolded outer membrane proteins (OMPs, through a C-terminal motif that has been speculated to be species-specific, based on theoretical and experimental results from only two species, Escherichia coli and Neisseria meningitidis, where it was shown on the basis of individual sequences and motifs that OMPs from the one cannot easily be over expressed in the other, unless the C-terminal motif was adapted. In order to determine whether this species specificity is a general phenomenon, we undertook a large-scale bioinformatics study on all predicted OMPs from 437 fully sequenced proteobacterial strains. Results We were able to verify the incompatibility reported between Escherichia coli and Neisseria meningitidis, using clustering techniques based on the pairwise Hellinger distance between sequence spaces for the C-terminal motifs of individual organisms. We noticed that the amino acid position reported to be responsible for this incompatibility between Escherichia coli and Neisseria meningitidis does not play a major role for determining species specificity of OMP recognition by the BAM complex. Instead, we found that the signal is more diffuse, and that for most organism pairs, the difference between the signals is hard to detect. Notable exceptions are the Neisseriales, and Helicobacter spp. For both of these organism groups, we describe the specific sequence requirements that are at the basis of the observed difference. Conclusions Based on the finding that the differences between the recognition motifs of almost all organisms are small, we assume that

Group B meningococcal vaccine science and policy.

Science.gov (United States)

Drysdale, Simon B; Pollard, Andrew J

2015-06-01

Capsular group B Neisseria meningitidis is one of the leading causes of death in developed countries. A new vaccine (4CMenB) has recently been developed which was found to have an acceptable safety profile in clinical studies and to be immunogenic. This review examines the evidence supporting the licensure of the 4CMenB vaccine and discusses recommendations for its use. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

The outer membrane protein assembly machinery of Neisseria meningitidis

NARCIS (Netherlands)

Volokhina, E.B.|info:eu-repo/dai/nl/304837202

2009-01-01

Gram-negative bacteria are characterized by a cell envelope consisting of an inner membrane (IM) and an outer membrane (OM), which are separated by the peptidoglycan-containing periplasm. While the integral IM proteins are alpha-helical, all but one known integral OM proteins (OMPs) are

Functional analysis of the Gonococcal Genetic Island of Neisseria gonorrhoeae.

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Emilia Pachulec

Full Text Available Neisseria gonorrhoeae is an obligate human pathogen that is responsible for the sexually-transmitted disease gonorrhea. N. gonorrhoeae encodes a T4SS within the Gonococcal Genetic Island (GGI, which secretes ssDNA directly into the external milieu. Type IV secretion systems (T4SSs play a role in horizontal gene transfer and delivery of effector molecules into target cells. We demonstrate that GGI-like T4SSs are present in other β-proteobacteria, as well as in α- and γ-proteobacteria. Sequence comparison of GGI-like T4SSs reveals that the GGI-like T4SSs form a highly conserved unit that can be found located both on chromosomes and on plasmids. To better understand the mechanism of DNA secretion by N. gonorrhoeae, we performed mutagenesis of all genes encoded within the GGI, and studied the effects of these mutations on DNA secretion. We show that genes required for DNA secretion are encoded within the yaa-atlA and parA-parB regions, while genes encoded in the yfeB-exp1 region could be deleted without any effect on DNA secretion. Genes essential for DNA secretion are encoded within at least four different operons.

Carriage rate of Neisseria meningitides among pupils of islamic ...

African Journals Online (AJOL)

The study was a cross-sectional study that determined the carriage rate of Neisseria meningitides among pupils of Islamic boarding schools (Tsangaya Almajirai) in Kano, Nigeria. Nasal swabs were randomly collected from 150 children aged 5 years to 10 years and above from three selected Tsangaya Almajiri schools in ...

Resistencia de Neisseria gonorrhoeae a ciprofloxacina según hábitos sexuales Ciprofloxacin resistance of Neisseria gonorrhoeae according to sexual habits

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Susana García

2008-10-01

Full Text Available En la Argentina los primeros hallazgos de Neisseria gonorrhoeae resistentes a las fluorquinolonas se documentaron en el año 2000. Desde enero de 2005 hasta junio de 2007, se evaluaron 595 hombres que tienen sexo con hombres (HSH y 571 varones heterosexuales para investigar la presencia de N. gonorrhoeae y la resistencia a los antimicrobianos. La prevalencia de gonorrea en HSH y varones heterosexuales fue 0.091(91/1000 en ambos grupos y el % de N. gonorrhoeae resistente a ciprofloxacina (NGRC fue 20.0% y 3.8% respectivamente (p: 0.0416. Trece de 106 aislamientos fueron NGRC, correspondieron a 11 HSH y 2 varones heterosexuales. Seis HSH presentaron uretritis, uno de ellos con localización simultánea en recto y cinco pacientes fueron asintomáticos (recto, 2; faringe, 2; uretra, 1. No se pudo demostrar relación epidemiológica entre ellos. Dos varones heterosexuales presentaron uretritis. Los 8 pacientes sintomáticos fueron tratados empíricamente con ciprofloxacina y se documentó fracaso de tratamiento. Estos y los portadores de NGRC recibieron tratamiento con 500 mg de ceftriaxona IM. Los controles postratamiento demostraron la erradicación del microorganismo. Los aislamientos de NGRC presentaron CIM de ciprofloxacina entre 2 y 32 µg/ml, todos fueron beta-lactamasa negativos, 4/13 presentaron resistencia cromosómica a penicilina (CIM= 1 µg/ml, y los rangos de CIM (µg/ml para los siguientes antibióticos fueron: penicilina: 0.016-1; tetraciclina: 0.125-2; ceftriaxona: 0.004-0.008; eritromicina: 0.032-2; azitromicina: 0.032-0.5; espectinomicina: 8-32. Dado el elevado porcentaje de aislamientos de NGRC en HSH en nuestro hospital, debería utilizarse otro antimicrobiano para el tratamiento empírico en estos pacientes.The first isolates of Neisseria gonorrhoeae resistant to fluorquinolones in Argentina were reported in 2000. Since January 2005 to June 2007 Neisseria gonorrhoeae was studied in 595 men who have sex with men (MSM and 571

Structure and Function of Neisseria gonorrhoeae MtrF Illuminates a Class of Antimetabolite Efflux Pumps

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Chih-Chia Su

2015-04-01

Full Text Available Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. N. gonorrhoeae MtrF is an integral membrane protein that belongs to the AbgT family of transporters for which no structural information is available. Here, we describe the crystal structure of MtrF, revealing a dimeric molecule with architecture distinct from all other families of transporters. MtrF is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins, posing a plausible pathway for substrate transport. A combination of the crystal structure and biochemical functional assays suggests that MtrF is an antibiotic efflux pump mediating bacterial resistance to sulfonamide antimetabolite drugs.

The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD

Science.gov (United States)

Calmettes, Charles; Ing, Christopher; Buckwalter, Carolyn M.; El Bakkouri, Majida; Chieh-Lin Lai, Christine; Pogoutse, Anastassia; Gray-Owen, Scott D.; Pomès, Régis; Moraes, Trevor F.

2015-01-01

Invading bacteria from the Neisseriaceae, Acinetobacteriaceae, Bordetellaceae and Moraxellaceae families express the conserved outer-membrane zinc transporter zinc-uptake component D (ZnuD) to overcome nutritional restriction imposed by the host organism during infection. Here we demonstrate that ZnuD is required for efficient systemic infections by the causative agent of bacterial meningitis, Neisseria meningitidis, in a mouse model. We also combine X-ray crystallography and molecular dynamics simulations to gain insight into the mechanism of zinc recognition and transport across the bacterial outer-membrane by ZnuD. Because ZnuD is also considered a promising vaccine candidate against N. meningitidis, we use several ZnuD structural intermediates to map potential antigenic epitopes, and propose a mechanism by which ZnuD can maintain high sequence conservation yet avoid immune recognition by altering the conformation of surface-exposed loops. PMID:26282243

FREKUENSI KUMAN Neisseriae gonorrhoeae YANG MENGINFEKSI WANITA USIA ANAK DI PADANG

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Elizabeth Bahar

2008-09-01

Full Text Available AbstrakInfeksi traktus reproduksi wanita dapat disebabkan oleh penyakit hubungan seksual (sifilis, gonore, trikhomonas dan sebagainya. Dari semua penyakit kelamin insidens gonore merupakan yang tertinggi. Gonore penyakit yang disebabkan oleh kuman Neisseriae gonorrhoea atau disebut juga Coccus Gram negatif sampai saat ini merupakan suatu penyakit yang banyak menimbulkan problem bukan saja di negara berkembang, tetapi juga merupakan masalah di negara super power (adikuasa bahkan di seluruh dunia. Selain mempengaruhi kesehatan reproduksi erat sekali hubungannya dengan perilaku seks. Dari sudut psikologi sosial sebagian besar perilaku seks adalah perilaku sosial.Telah dilakukan penelitian dengan pengumpulan sampel secara cross sectional sampling dari wanita usia anak di Padang untuk mengetahui adanya kuman Neisseriae gonorrhoeae. Penelitian deskriptif dengan menggunakan metoda pewarnaan Gram mikroskopis langsung. Dari 18 sampel, ditemukan frekuensi penderita terinfeksi kuman Neisseriae gonorrhoeae 11 (61% dan 7 (38,9% non N gonorrhoeae. Dari variable-variable yang diuji anak sebagai sample yang terinfeksi kuman gonore berusia 1 – 3 tahun 4 (22,2 %, 4 – 7 tahun 6 (33,3%, 8 – 11 tahun 1 (5,5%} dan 12 – 15 tahun 0 (0%, di mana di lihat tingkat usia pendidikan anak pra sekolah dan sekolah. Orang tua si anak, ibu dan ayah pendidikan mencakup SD 0 (0%, SLP 0 (0%, SLA 14 (77,8 dan 7 (38,9% dan PT 4 (22,2% dan 10 (55,5 %. Kemudian pekerjaan orang tua anak meliputi RT 9 (50%, PNS/Swasta 8 (44,4% dan 14 (77,8%. Dagang 1 (5,6% dan 2 (11,1% dan sopir 2 (11,1%. Kesimpulannya penderita wanita usia anak di Padang cukup tinggi terinfeksi kuman N gonorrhoeae.Kata Kunci : gonore, wanita usia anak-anak, resistensi antibiotika.AbstractFemale genital infection may causes by sexual transmitted diseases (Syphilis, gonorrhoea, ect. From all vebereal diseases, incidence of gonorrhoeae is the highest. Current gonorrhoeae caused by Neisseriae gonorrhoeae or Gram

Frequency of Pathogenic Paediatric Bacterial Meningitis in Mozambique: The Critical Role of Multiplex Real-Time Polymerase Chain Reaction to Estimate the Burden of Disease.

Science.gov (United States)

Nhantumbo, Aquino Albino; Cantarelli, Vlademir Vicente; Caireão, Juliana; Munguambe, Alcides Moniz; Comé, Charlotte Elizabeth; Pinto, Gabriela do Carmo; Zimba, Tomás Francisco; Mandomando, Inácio; Semá, Cynthia Baltazar; Dias, Cícero; Moraes, Milton Ozório; Gudo, Eduardo Samo

2015-01-01

In Sub-Saharan Africa, including Mozambique, acute bacterial meningitis (ABM) represents a main cause of childhood mortality. The burden of ABM is seriously underestimated because of the poor performance of culture sampling, the primary method of ABM surveillance in the region. Low quality cerebrospinal fluid (CSF) samples and frequent consumption of antibiotics prior to sample collection lead to a high rate of false-negative results. To our knowledge, this study is the first to determine the frequency of ABM in Mozambique using real-time polymerase chain reaction (qPCR) and to compare results to those of culture sampling. Between March 2013 and March 2014, CSF samples were collected at 3 regional hospitals from patients under 5 years of age, who met World Health Organization case definition criteria for ABM. Macroscopic examination, cytochemical study, culture, and qPCR were performed on all samples. A total of 369 CSF samples were collected from children clinically suspected of ABM. qPCR showed a significantly higher detection rate of ABM-causing pathogens when compared to culture (52.3% [193/369] versus 7.3% [27/369], p = 0.000). The frequency of Streptococcus pneumoniae, Haemophilus influenzae, group B Streptococci, and Neisseria meningitidis were 32.8% (121⁄369), 12.2%, (45⁄369), 3.0% (16⁄369) and 4.3% (11⁄369), respectively, significantly higher compared to that obtained on culture (p < 0.001 for each). Our findings demonstrate that culture is less effective for the diagnosis of ABM than qPCR. The common use of culture rather than qPCR to identify ABM results in serious underestimation of the burden of the disease, and our findings strongly suggest that qPCR should be incorporated into surveillance activities for ABM. In addition, our data showed that S. pneumoniae represents the most common cause of ABM in children under 5 years of age.

A computational genomics pipeline for prokaryotic sequencing projects.

Science.gov (United States)

Kislyuk, Andrey O; Katz, Lee S; Agrawal, Sonia; Hagen, Matthew S; Conley, Andrew B; Jayaraman, Pushkala; Nelakuditi, Viswateja; Humphrey, Jay C; Sammons, Scott A; Govil, Dhwani; Mair, Raydel D; Tatti, Kathleen M; Tondella, Maria L; Harcourt, Brian H; Mayer, Leonard W; Jordan, I King

2010-08-01

New sequencing technologies have accelerated research on prokaryotic genomes and have made genome sequencing operations outside major genome sequencing centers routine. However, no off-the-shelf solution exists for the combined assembly, gene prediction, genome annotation and data presentation necessary to interpret sequencing data. The resulting requirement to invest significant resources into custom informatics support for genome sequencing projects remains a major impediment to the accessibility of high-throughput sequence data. We present a self-contained, automated high-throughput open source genome sequencing and computational genomics pipeline suitable for prokaryotic sequencing projects. The pipeline has been used at the Georgia Institute of Technology and the Centers for Disease Control and Prevention for the analysis of Neisseria meningitidis and Bordetella bronchiseptica genomes. The pipeline is capable of enhanced or manually assisted reference-based assembly using multiple assemblers and modes; gene predictor combining; and functional annotation of genes and gene products. Because every component of the pipeline is executed on a local machine with no need to access resources over the Internet, the pipeline is suitable for projects of a sensitive nature. Annotation of virulence-related features makes the pipeline particularly useful for projects working with pathogenic prokaryotes. The pipeline is licensed under the open-source GNU General Public License and available at the Georgia Tech Neisseria Base (http://nbase.biology.gatech.edu/). The pipeline is implemented with a combination of Perl, Bourne Shell and MySQL and is compatible with Linux and other Unix systems.

Eight-plex PCR and liquid-array detection of bacterial and viral pathogens in cerebrospinal fluid from patients with suspected meningitis

DEFF Research Database (Denmark)

Bøving, Mette Kusk; Pedersen, Lisbeth Nørum; Møller, Jens Kjølseth

2009-01-01

pneumoniae, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Streptococcus agalactiae, herpes simplex virus types 1 and 2, and varicella-zoster virus. The study was based on 1,187 samples, of which 55 were found to be positive by PCR. The assay was found to have an excellent sensitivity...... and an excellent specificity compared to the results of a "gold standard," defined by routine laboratory tests, for the two most important pathogens, S. pneumoniae (95 and 99.1%, respectively) and N. meningitidis (100 and 99.7%, respectively). The method provides a valuable supplement to the traditional microscopy...

Comparison of the cystine-tryptic digest agar-carbohydrate co-agglutination and BACTEC Neisseria differentiation methods for identification of Neisseria gonorrhoeae in the clinical laboratory

International Nuclear Information System (INIS)

Morello, J.A.; Beheshti, S.; Bohnhoff, M.

1980-01-01

The author evaluated CTA-carbohydrate, BACTEC and co-agglutination systems to determine their accuracy for identifying N. gonorrhoeae strains and for distinguishing them from other Neisseria species. BACTEC is a radiometric assay based on the measurement of liberated radiolabelled CO 2 from metabolised carbohydrates which have been tagged with 14 C. (Auth.)

Neisseria gonorrhoeae strain with reduced susceptibilities to extended-spectrum cephalosporins.

Science.gov (United States)

Nguyen, Duylinh; Gose, Severin; Castro, Lina; Chung, Kathleen; Bernstein, Kyle; Samuel, Micheal; Bauer, Heidi; Pandori, Mark

2014-07-01

The spread of Neisseria gonorrhoeae strains with reduced susceptibility to extended-spectrum cephalosporins is an increasing public health threat. Using Etest and multiantigen sequence typing, we detected sequence type 1407, which is associated with reduced susceptibilities to extended-spectrum cephalosporins, in 4 major populated regions in California, USA, in 2012.

Molecular epidemiology of Neisseria gonorrhoeae strains circulating in Indonesia using multi-locus variable number tandem repeat analysis (MLVA) and Neisseria gonorrhoeae multi-antigen sequence typing (NG-NAST) techniques

NARCIS (Netherlands)

Hananta, I. Putu Yuda; van Dam, Alje Pieter; Schim van der Loeff, Maarten Franciscus; Dierdorp, Mirjam; Wind, Carolien Marleen; Soebono, Hardyanto; de Vries, Henry John Christiaan; Bruisten, Sylvia Maria

2018-01-01

Background: Control of gonorrhea in resource-limited countries, such as Indonesia, is mostly unsuccessful. Examining Neisseria gonorrhoeae (Ng) transmission networks using strain typing might help prioritizing public health interventions. Methods: In 2014, urogenital Ng strains were isolated from

Toward the use of genomics to study microevolutionary change in bacteria.

LENUS (Irish Health Repository)

Falush, Daniel

2009-10-01

Bacteria evolve rapidly in response to the environment they encounter. Some environmental changes are experienced numerous times by bacteria from the same population, providing an opportunity to dissect the genetic basis of adaptive evolution. Here I discuss two examples in which the patterns of rapid change provide insight into medically important bacterial phenotypes, namely immune escape by Neisseria meningitidis and host specificity of Campylobacter jejuni. Genomic analysis of populations of bacteria from these species holds great promise but requires appropriate concepts and statistical tools.

Hemoculturas positivas num serviço de pediatria: 2003-2012

Directory of Open Access Journals (Sweden)

Carla Garcez

2016-06-01

Conclusão: Nos 10 anos analisados, as bactérias mais frequentes foram: Staphylococcus aureus, Streptococcus pneumoniae e Escherichia coli. Verificou-se diminuição da incidência da Neisseria meningitidis após 2005 e do Streptococcus pneumoniae após 2007. As suscetibilidades das diferentes bactérias patogénicas aos antimicrobianos mantiveram-se estáveis. Enfatiza-se a importância epidemiológica e clínica da monitorização de dados microbiológicos.

A designated centre for people with disabilities operated by Peter Bradley Foundation Limited, Cork

LENUS (Irish Health Repository)

Falush, Daniel

2009-10-01

Bacteria evolve rapidly in response to the environment they encounter. Some environmental changes are experienced numerous times by bacteria from the same population, providing an opportunity to dissect the genetic basis of adaptive evolution. Here I discuss two examples in which the patterns of rapid change provide insight into medically important bacterial phenotypes, namely immune escape by Neisseria meningitidis and host specificity of Campylobacter jejuni. Genomic analysis of populations of bacteria from these species holds great promise but requires appropriate concepts and statistical tools.

A designated centre for people with disabilities operated by KARE, promoting inclusion for people with intellectual disabilities, Kildare

LENUS (Irish Health Repository)

Falush, Daniel

2009-10-01

Bacteria evolve rapidly in response to the environment they encounter. Some environmental changes are experienced numerous times by bacteria from the same population, providing an opportunity to dissect the genetic basis of adaptive evolution. Here I discuss two examples in which the patterns of rapid change provide insight into medically important bacterial phenotypes, namely immune escape by Neisseria meningitidis and host specificity of Campylobacter jejuni. Genomic analysis of populations of bacteria from these species holds great promise but requires appropriate concepts and statistical tools.

Toward the use of genomics to study microevolutionary change in bacteria.

Directory of Open Access Journals (Sweden)

Daniel Falush

2009-10-01

Full Text Available Bacteria evolve rapidly in response to the environment they encounter. Some environmental changes are experienced numerous times by bacteria from the same population, providing an opportunity to dissect the genetic basis of adaptive evolution. Here I discuss two examples in which the patterns of rapid change provide insight into medically important bacterial phenotypes, namely immune escape by Neisseria meningitidis and host specificity of Campylobacter jejuni. Genomic analysis of populations of bacteria from these species holds great promise but requires appropriate concepts and statistical tools.

The monomeric form of Neisseria DNA mimic protein DMP19 prevents DNA from binding to the histone-like HU protein

Science.gov (United States)

Ko, Tzu-Ping; Liao, Yi-Ting; Hsu, Kai-Cheng

2017-01-01

DNA mimicry is a direct and effective strategy by which the mimic competes with DNA for the DNA binding sites on other proteins. Until now, only about a dozen proteins have been shown to function via this strategy, including the DNA mimic protein DMP19 from Neisseria meningitides. We have shown previously that DMP19 dimer prevents the operator DNA from binding to the transcription factor NHTF. Here, we provide new evidence that DMP19 monomer can also interact with the Neisseria nucleoid-associated protein HU. Using BS3 crosslinking, gel filtration and isothermal titration calorimetry assays, we found that DMP19 uses its monomeric form to interact with the Neisseria HU dimer. Crosslinking conjugated mass spectrometry was used to investigate the binding mode of DMP19 monomer and HU dimer. Finally, an electrophoretic mobility shift assay (EMSA) confirmed that the DNA binding affinity of HU is affected by DMP19. These results showed that DMP19 is bifunctional in the gene regulation of Neisseria through its variable oligomeric forms. PMID:29220372

A misleading false-negative result using Neisseria gonorrhoeae opa MGB multiplex PCR assay in patient's rectal sample due to partial mutations of the opa gene.

Science.gov (United States)

Vahidnia, Ali; van Empel, Pieter Jan; Costa, Sandra; Oud, Rob T N; van der Straaten, Tahar; Bliekendaal, Harry; Spaargaren, Joke

2015-07-01

A 53-year-old homosexual man presented at his general practitioner (GP) practice with a suspicion of sexually transmitted infection. Initial NAAT screening was performed for Chlamydia trachomatis and Neisseria gonorrhoeae. The patient was positive for Neisseria gonorrhoeae both for his urine and rectal sample. The subsequent confirmation test for Neisseria gonorrhoeae by a second laboratory was only confirmed for the urine sample and the rectal sample was negative. We report a case of a potential false-negative diagnosis of Neisseria gonorrhoeae due to mutations of DNA sequence in the probe region of opa-MGB assay of the rectal sample. The patient did not suffer any discomfort as diagnosis of Neisseria gonorrhoeae in his urine sample had already led to treatment by prescribing the patient with Ceftriaxone 500 mg IV dissolved in 1 ml lidocaine 2% and 4 mL saline. The patient also received a prescription for Azithromycin (2x500 mg).

Phase variation of Opa proteins of Neisseria meningitidis and the ...

Indian Academy of Sciences (India)

2016-08-26

Aug 26, 2016 ... Manish Sadarangani1 J Claire Hoe1 Katherine Makepeace1 Peter Van Der Ley2 Andrew J Pollard1. Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford OX3 7LE, UK; Institute for Translational Vaccinology ...

Outbreak of serotype W135 Neisseria meningitidis in central river ...

African Journals Online (AJOL)

2012-06-21

Jun 21, 2012 ... References. 1. Gambia Ministry of Health and Social welfare. Epidemiology and disease control unit Banjul; 2012. 2. World Health Organization. Control of epidemic meningococcal disease. In: Practical Guidelines. 2nd ed. Geneva: World Health Organization; 1998. Available from: http://www.who.int/emc.

Screening for Sexually Transmitted Infection Pathogens in Semen Samples

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RW Peeling

2005-01-01

Full Text Available The transmission of sexually transmitted infection (STI pathogens from an infected donor to the recipient of a semen donation in assisted conception may result not only in acute infection but also in long-term reproductive complications or adverse outcomes of pregnancy, including infection of the offspring. Screening for bacterial STI pathogens, Chlamydia trachomatis and Neisseria gonorrhoeae is strongly recommended because these pathogens can cause serious reproductive complications in the recipients of semen donations and infection in their offspring. Screening for these pathogens should be performed using the most sensitive methods, such as nucleic acid amplified tests. False-negative results due to inhibitory substances in the semen sample should be monitored using amplification controls. Where specimen transport is not a problem and culture facilities are available, N gonorrhoeae can also be detected by culture. Laboratories performing screening should subscribe to proficiency programs and have strict quality controls. Although Trichomonas vaginalis, group B streptococcus and genital mycoplasmas have been associated with adverse outcomes of pregnancy, the frequent finding of these organisms in healthy individuals brings into question the validity of mandatory inclusion of these organisms in the screening panel. Although viral STI pathogens and Treponema pallidum -- the causative agent of syphilis -- may be detected in semen, their presence may be more sensitively detected through antibody testing of the donor. Screening donors for HIV, hepatitis B and syphilis by serology is uniformly recommended in all of the guidelines, but the value of screening either donors or semen samples for cytomegalovirus, herpes simplex viruses and human papilloma viruses is less clear.

Primary Meningococcal Polyarthritis in an Adult Woman

Directory of Open Access Journals (Sweden)

José Celso Giordan Cavalcanti Sarinho

2015-01-01

Full Text Available Primary joint infection caused by the Gram-negative bacteria Neisseria meningitidis is rare. Normally, joint involvement comes secondary to meningitis or severe sepsis caused by this agent. When primary arthritis is seen, monoarthritis is the most common presentation. A meningococcal polyarthritis is described in less than 10 case reports according to current literature. This case report aims to briefly review this rare clinical event in an adult woman with no previous history of rheumatological disease. Early diagnosis of polyarthritis caused by meningococcal bacteria usually present a good prognosis when properly treated.

The first report: An analysis of bacterial flora of the first voided urine specimens of patients with male urethritis using the 16S ribosomal RNA gene-based clone library method.

Science.gov (United States)

You, Chunlin; Hamasuna, Ryoichi; Ogawa, Midori; Fukuda, Kazumasa; Hachisuga, Toru; Matsumoto, Tetsuro; Taniguchi, Hatsumi

2016-06-01

To analyse the bacterial flora of urine from patients with male urethritis using the clone library method. Urine specimens from patients with urethritis were used. The bacterial flora was analysed according to the 16S ribosomal RNA gene-based clone library method. In addition, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum or Ureaplasma parvum were detected by the conventional PCR methods (TMA or real-time PCR) and data from the clone library and conventional PCR methods were compared. Among 58 urine specimens, 38 were successfully analysed using the clone library method. From the specimens, 2427 clones were evaluated and 95 bacterial phylotypes were detected. N. gonorrhoeae was detected from 6 specimens and as the predominant bacterial species in 5 specimens. M. genitalium was detected from 5 specimens and as the predominant bacterial species in 3 specimens. C. trachomatis was detected from 15 specimens using the TMA method, but was detected from only 1 specimen using the clone library method. U. parvum was detected from only 2 specimens using the clone library method. In addition, Haemophilus influenzae and Neisseria meningitidis were also detected in 8 and 1 specimens, respectively. Gardnerella vaginalis, which is a potential pathogen for bacterial vaginitis in women, was detected in 10 specimens. The clone library method can detect the occupancy rate of each bacteria species among the bacterial flora and may be a new method for bacterial analyses in male urethritis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

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Jacqueline M. Miller

2011-01-01

Full Text Available Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.

Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

Science.gov (United States)

Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela

2011-01-01

Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles. PMID:21991444

Vaccine preventable meningitis in Malaysia: epidemiology and management.

Science.gov (United States)

McNeil, Hannah C; Jefferies, Johanna M C; Clarke, Stuart C

2015-06-01

Worldwide bacterial meningitis accounts for more than one million cases and 135,000 deaths annually. Profound, lasting neurological complications occur in 9-25% of cases. This review confirms the greatest risk from bacterial meningitis is in early life in Malaysia. Much of the disease burden can be avoided by immunization, particularly against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Despite inclusion of the Hib vaccine in the National Immunisation Programme and the licensure of pneumococcal vaccines, these two species are the main contributors to bacterial meningitis in Malaysia, with Neisseria meningitidis and Mycobacterium tuberculosis, causing a smaller proportion of disease. The high Hib prevalence may partly be due to dated, small-scale studies limiting the understanding of the current epidemiological situation. This highlights the need for larger, better quality surveillance from Malaysia to evaluate the success of Hib immunization and to help guide immunization policy for vaccines against S. pneumoniae and N. meningitidis.

Bacterial Meningitis in the Absence of Cerebrospinal Fluid Pleocytosis: A Case Report and Review of the Literature

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Ryota Hase

2014-01-01

Full Text Available Elevation of cerebrospinal fluid (CSF cell count is a key sign in the diagnosis of bacterial meningitis. However, there have been reports of bacterial meningitis with no abnormalities in initial CSF testing. This type of presentation is extremely rare in adult patients. Here, a case involving an 83-year-old woman who was later diagnosed with bacterial meningitis caused by Neisseria meningitidis is described, in whom CSF at initial and second lumbar puncture did not show elevation of cell counts. Twenty-six non-neutropenic adult cases of bacterial meningitis in the absence of CSF pleocytosis were reviewed. The frequent causative organisms were Streptococcus pneumoniae and N meningitidis. Nineteen cases had bacteremia and seven died. The authors conclude that normal CSF at lumbar puncture at an early stage cannot rule out bacterial meningitis. Therefore, repeat CSF analysis should be considered, and antimicrobial therapy must be started immediately if there are any signs of sepsis or meningitis.

Trend of bacterial meningitis in Bahrain from 1990 to 2013 and effect of introduction of new vaccines.

Science.gov (United States)

Saeed, N; AlAnsari, H; AlKhawaja, S; Jawad, J S; Nasser, K; AlYousef, E

2016-06-15

Meningitis is among the 10 commonest infectious causes of death worldwide. This retrospective analysis of reported cases of meningitis in Bahrain aimed to assess the trend in the incidence of bacterial meningitis from 1990 to 2013, before and after the introduction of new vaccines. Of 1455 reported cases of meningitis during the study period 73.1% were viral and 26.9% were bacterial etiology (tuberculous meningitis 8.3%; Streptococcus pneumoniae 4.9%, Haemophilus influenzae 3.6% and Neisseria meningitidis 1.7%). There was a peak of meningitis cases in 1995-1996. The incidence of meningitis due to H. influenzae and N. meningitidis showed a marked reduction after the introduction of the corresponding vaccines in 1998 and 2001 respectively, and S. pneumoniae became the predominant organism after Mycobacterium tuberculosis. The changing trend in the etiology of bacterial meningitis points to the need to study vaccination programme modifications, such as pneumococcal vaccine for the adult population, especially high-risk groups.

The use of oligonucleotide probes for meningococcal serotype characterization

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SACCHI Claudio Tavares

1998-01-01

Full Text Available In the present study we examine the potential use of oligonucleotide probes to characterize Neisseria meningitidis serotypes without the use of monoclonal antibodies (MAbs. Antigenic diversity on PorB protein forms the bases of serotyping method. However, the current panel of MAbs underestimated, by at least 50% the PorB variability, presumably because reagents for several PorB variable regions (VRs are lacking, or because a number of VR variants are not recognized by serotype-defining MAbs12. We analyzed the use of oligonucleotide probes to characterize serotype 10 and serotype 19 of N. meningitidis. The porB gene sequence for the prototype strain of serotype 10 was determined, aligned with 7 other porB sequences from different serotypes, and analysis of individual VRs were performed. The results of DNA probes 21U (VR1-A and 615U (VR3-B used against 72 N. meningitidis strains confirm that VR1 type A and VR3 type B encode epitopes for serotype-defined MAbs 19 and 10, respectively. The use of probes for characterizing serotypes possible can type 100% of the PorB VR diversity. It is a simple and rapid method specially useful for analysis of large number of samples.

Molecular basis of the amylose-like polymer formation catalyzed by Neisseria polysaccharea amylosucrase

DEFF Research Database (Denmark)

Albenne, Cécile; Skov, Lars; Mirza, Osman Asghar

2004-01-01

Amylosucrase from Neisseria polysaccharea is a remarkable transglucosidase from family 13 of the glycoside-hydrolases that synthesizes an insoluble amylose-like polymer from sucrose in the absence of any primer. Amylosucrase shares strong structural similarities with alpha-amylases. Exactly how...

Neisseria gonorrhoeae: testing, typing and treatment in an era of increased antimicrobial resistance

NARCIS (Netherlands)

Wind, C.M.

2017-01-01

This thesis discusses the management of Neisseria gonorrhoeae infections while under threat of emerging antimicrobial resistance. It focuses on improved diagnostics, and antimicrobial resistance to current and future therapies. We describe a new method of targeted deferred culture, using nucleic

[Investigation of bacterial and viral etiology in community acquired central nervous system infections with molecular methods].

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Kahraman, Hasip; Tünger, Alper; Şenol, Şebnem; Gazi, Hörü; Avcı, Meltem; Örmen, Bahar; Türker, Nesrin; Atalay, Sabri; Köse, Şükran; Ulusoy, Sercan; Işıkgöz Taşbakan, Meltem; Sipahi, Oğuz Reşat; Yamazhan, Tansu; Gülay, Zeynep; Alp Çavuş, Sema; Pullukçu, Hüsnü

2017-07-01

In this multicenter prospective cohort study, it was aimed to evaluate the bacterial and viral etiology in community-acquired central nervous system infections by standart bacteriological culture and multiplex polymerase chain reaction (PCR) methods. Patients hospitalized with central nervous system infections between April 2012 and February 2014 were enrolled in the study. Demographic and clinical information of the patients were collected prospectively. Cerebrospinal fluid (CSF) samples of the patients were examined by standart bacteriological culture methods, bacterial multiplex PCR (Seeplex meningitis-B ACE Detection (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Group B streptococci) and viral multiplex PCR (Seeplex meningitis-V1 ACE Detection kits herpes simplex virus-1 (HSV1), herpes simplex virus-2 (HSV2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein Barr virus (EBV) and human herpes virus 6 (HHV6)) (Seeplex meningitis-V2 ACE Detection kit (enteroviruses)). Patients were classified as purulent meningitis, aseptic meningitis and encephalitis according to their clinical, CSF (leukocyte level, predominant cell type, protein and glucose (blood/CSF) levels) and cranial imaging results. Patients who were infected with a pathogen other than the detection of the kit or diagnosed as chronic meningitis and other diseases during the follow up, were excluded from the study. A total of 79 patients (28 female, 51 male, aged 42.1 ± 18.5) fulfilled the study inclusion criteria. A total of 46 patients were classified in purulent meningitis group whereas 33 were in aseptic meningitis/encephalitis group. Pathogens were detected by multiplex PCR in 41 patients. CSF cultures were positive in 10 (21.7%) patients (nine S.pneumoniae, one H.influenzae) and PCR were positive for 27 (58.6%) patients in purulent meningitis group. In this group one type of bacteria were detected in 18 patients (14 S.pneumoniae, two N.meningitidis

Antimicrobial Resistance Expressed by Neisseria gonorrhoeae: A Major Global Public Health Problem in the 21st Century.

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Unemo, Magnus; Del Rio, Carlos; Shafer, William M

2016-06-01

Neisseria gonorrhoeae is a strictly human pathogen that is typically transmitted by sexual contact. The associated disease gonorrhea has plagued humankind for thousands of years, with a current estimated incidence of 78 million cases per year. Advances in antimicrobial discovery in the 1920s and 1930s leading to the discovery of sulfonamides and penicillin begun the era of effective antimicrobial treatment of gonorrhea. Unfortunately, the gonococcus developed decreased susceptibility or even resistance to these initially employed antibiotics, a trend that continued over subsequent decades with each new antibiotic that was brought into clinical practice. As this pattern of resistance has continued into the 21st century, there is now reason for great concern, especially in an era when few new antibiotics have prospects for use as treatment of gonorrhea. Here, we review the history of gonorrhea treatment regimens and gonococcal resistance to antibiotics, the mechanisms of resistance, resistance monitoring schemes that exist in different international settings, global responses to the challenge of resistance, and prospects for future treatment regimens in the 21st century.

Comparison of four techniques for the confirmatory identification of Neisseria gonorrhoeae

International Nuclear Information System (INIS)

Jacobs, P.F.

1980-01-01

The authors have compared four assay techniques for the confirmatory identification of Neisseria gonorrhoeae. On of these is a radiometric assay, based on the measurement of liberated radiolabelled CO 2 from metabolized carbohydrates which have been tagged with 14 C. The assay uses glucose, maltose and fructose as its differentiating sugars, plus the ONPG reaction, and can be read in three hours. (Auth.)

Design of a multiplex PCR assay for the simultaneous detection and confirmation of Neisseria gonorrhoeae.

LENUS (Irish Health Repository)

O'Callaghan, Isabelle

2010-05-01

To improve the detection of Neisseria gonorrhoeae by designing a multiplex PCR assay using two N gonorrhoeae-specific genes as targets, thereby providing detection and confirmation of a positive result simultaneously.

Menjugate (Chiron).

Science.gov (United States)

Jones, D H

2001-01-01

Chiron has developed and launched Menjugate, a vaccine for the treatment for meningococcus C infections caused by the pathogen Neisseria meningitidis [177064]. In August 1999, Chiron filed with the UK MCA for a license to market Menjugate. The licence was granted in March 2000 [339082], [344773], [357897] and as of April 2000, a vaccination program was underway in the UK [362152]. Menjugate is indicated for children of 12 months and older, but Chiron was expecting approval in the US for infants younger than 12 months by the end of 2000. The company will also pursue mutual recognition in Europe [376204]. In August 2000, Chiron received marketing clearance for Menjugate from the Irish Medicines Board as a conjugate against meningococcal C disease [378353]. The vaccine employs CRM-conjugate technology, whereby a diphtheria toxoid is used as a carrier protein for the meningitis C-specific antigens. The vaccine is being developed for its potential to provide protection against meningitis in both adults and infants. In July 2000, Chiron entered into a comarketing and co-promotion agreement with Aventis Pasteur under which Aventis will assist Chiron in marketing and sales efforts for Menjugate in the UK [374760].

Rapid change in the ciprofloxacin resistance pattern among Neisseria gonorrhoeae strains in Nuuk, Greenland

DEFF Research Database (Denmark)

Skjerbæk Rolskov, Anne; Bjorn-Mortensen, Karen; Mulvad, Gert

2015-01-01

OBJECTIVES: Sexually transmitted infections (STIs), including infections with Neisseria gonorrhoeae (GC), are highly incident in Greenland. Since January 2011, GC testing has been performed on urine with nucleic acid amplification tests (NAATs) by strand displacement amplification (Becton Dickins...

Fuzzy species among recombinogenic bacteria

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Fraser Christophe

2005-03-01

Full Text Available Abstract Background It is a matter of ongoing debate whether a universal species concept is possible for bacteria. Indeed, it is not clear whether closely related isolates of bacteria typically form discrete genotypic clusters that can be assigned as species. The most challenging test of whether species can be clearly delineated is provided by analysis of large populations of closely-related, highly recombinogenic, bacteria that colonise the same body site. We have used concatenated sequences of seven house-keeping loci from 770 strains of 11 named Neisseria species, and phylogenetic trees, to investigate whether genotypic clusters can be resolved among these recombinogenic bacteria and, if so, the extent to which they correspond to named species. Results Alleles at individual loci were widely distributed among the named species but this distorting effect of recombination was largely buffered by using concatenated sequences, which resolved clusters corresponding to the three species most numerous in the sample, N. meningitidis, N. lactamica and N. gonorrhoeae. A few isolates arose from the branch that separated N. meningitidis from N. lactamica leading us to describe these species as 'fuzzy'. Conclusion A multilocus approach using large samples of closely related isolates delineates species even in the highly recombinogenic human Neisseria where individual loci are inadequate for the task. This approach should be applied by taxonomists to large samples of other groups of closely-related bacteria, and especially to those where species delineation has historically been difficult, to determine whether genotypic clusters can be delineated, and to guide the definition of species.

Evaluation of a TaqMan Array Card for Detection of Central Nervous System Infections.

Science.gov (United States)

Onyango, Clayton O; Loparev, Vladimir; Lidechi, Shirley; Bhullar, Vinod; Schmid, D Scott; Radford, Kay; Lo, Michael K; Rota, Paul; Johnson, Barbara W; Munoz, Jorge; Oneko, Martina; Burton, Deron; Black, Carolyn M; Neatherlin, John; Montgomery, Joel M; Fields, Barry

2017-07-01

Infections of the central nervous system (CNS) are often acute, with significant morbidity and mortality. Routine diagnosis of such infections is limited in developing countries and requires modern equipment in advanced laboratories that may be unavailable to a number of patients in sub-Saharan Africa. We developed a TaqMan array card (TAC) that detects multiple pathogens simultaneously from cerebrospinal fluid. The 21-pathogen CNS multiple-pathogen TAC (CNS-TAC) assay includes two parasites ( Balamuthia mandrillaris and Acanthamoeba ), six bacterial pathogens ( Streptococcus pneumonia e, Haemophilus influenzae , Neisseria meningitidis , Mycoplasma pneumoniae , Mycobacterium tuberculosis , and Bartonella ), and 13 viruses (parechovirus, dengue virus, Nipah virus, varicella-zoster virus, mumps virus, measles virus, lyssavirus, herpes simplex viruses 1 and 2, Epstein-Barr virus, enterovirus, cytomegalovirus, and chikungunya virus). The card also includes human RNase P as a nucleic acid extraction control and an internal manufacturer control, GAPDH (glyceraldehyde-3-phosphate dehydrogenase). This CNS-TAC assay can test up to eight samples for all 21 agents within 2.5 h following nucleic acid extraction. The assay was validated for linearity, limit of detection, sensitivity, and specificity by using either live viruses (dengue, mumps, and measles viruses) or nucleic acid material (Nipah and chikungunya viruses). Of 120 samples tested by individual real-time PCR, 35 were positive for eight different targets, whereas the CNS-TAC assay detected 37 positive samples across nine different targets. The CNS-TAC assays showed 85.6% sensitivity and 96.7% specificity. Therefore, the CNS-TAC assay may be useful for outbreak investigation and surveillance of suspected neurological disease. Copyright © 2017 American Society for Microbiology.

Native Mitral Valve Endocarditis Caused by Neisseria elongata subsp. nitroreducens in a Patient with Marfan Syndrome: First Case in Italy and Review of the Literature

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Parrinello Rossella

2016-01-01

Full Text Available Neisseria elongata (NE is an aerobic Gram-negative organism that constitutes part of the commensal human normal oropharyngeal flora. Although previously considered not to be pathogenic, it has been recognized as an occasional cause of significant infections in humans. We report here the first case in Italy of infective endocarditis of a native prolapsing mitral valve in a patient with Marfan syndrome, caused by NE subspecies nitroreducens which has been rarely isolated from clinical specimens. The culprit organism has been confirmed by mass spectrometry directly from the positive blood culture, as previously reported. The amplified gene has been deposited in GenBank under accession number KT591873. In spite of the reported aggressive nature of NE, clinical remission was promptly obtained, there being no requirement for surgery.

Neisseria lactamica Causing a Lung Cavity and Skin Rash in a Renal Transplant Patient: First Report from India

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Khalid Hamid Changal

2016-01-01

Full Text Available Neisseria lactamica, a commensal, has been very rarely reported to cause diseases in immunocompromised hosts. In medical literature, there is only one report of a cavitatory lung lesion caused by it. The patient was a kidney transplant recipient. Neisseria lactamica was found to be the cause of his pulmonary cavity and a desquamating rash on feet. With the rapidly spreading medical advance, more and more patients are getting organ transplants, so the population of immunocompromised people is on the rise. We expect more sinister and less expected organisms to cause diseases in patients who have organ transplants.

Efectividad de la vacuna VA-MENGOC-BC® contra cepas heterólogas de meningococo B

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Rolando Ochoa-Azze

2016-08-01

Full Text Available La efectividad de las vacunas de vesículas de membrana externa de Neisseria meningitidis serogrupo B ha sido cuestionada por algunos investigadores, limitándola a la cepa vacunal. VA-MENGOC-BC® es una vacuna antimeningocócica basada en dicha tecnología. Presentamos un metaanálisis de estudios realizados en diferentes contextos epidemiológicos, evaluando su efectividad contra cepas heterólogas de meningococo B en varios grupos de edades. Se demuestra que la vacuna es efectiva contra cepas homólogas, heterólogas y de diferentes complejos clonales.

[THE NATIONAL NUTRIENT MEDIUM FOR DIAGNOSTIC OF PURULENT BACTERIAL MENINGITIS].

Science.gov (United States)

Podkopaev, Ya V; Domotenko, L V; Morozova, T P; Khramov, M K; Shepelin, A P

2015-05-01

The national growth mediums were developed for isolating and cultivating of main agents of purulent bacterial meningitis--haemophilus agar, chocolate agar, PBM-agar. The growing and selective characteristics of developed growth mediums are examined. The haemophilus agar ensures growth of Haemophilus influenzae. The chocolate agar, PBM-agar ensure growth of Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae. By growing characteristics, the national growth mediums match foreign analogues. Under application of growth mediums with selective additions it is possible to achieve selective isolation of main agents of purulent bacterial meningitis with inhibition of growth of microbes-associates.

Cleavage of a recombinant human immunoglobulin A2 (IgA2)-IgA1 hybrid antibody by certain bacterial IgA1 proteases

DEFF Research Database (Denmark)

Senior, B; Dunlop, JI; Batten, MR

2000-01-01

, Streptococcus pneumoniae, S. sanguis, Neisseria meningitidis types 1 and 2, N. gonorrhoeae types 1 and 2, and Haemophilus influenzae type 2. Thus, for these enzymes the recognition site for IgA1 cleavage is contained within half of the IgA1 hinge region; additional distal elements, if required, are provided...... by either an IgA1 or an IgA2 framework. In contrast, the IgA2/A1 hybrid appeared to be resistant to cleavage with S. oralis and some H. influenzae type 1 IgA1 proteases, suggesting these enzymes require additional determinants for efficient substrate recognition....

Nationwide surveillance of the antimicrobial susceptibility of Neisseria gonorrhoeae from male urethritis in Japan.

Science.gov (United States)

Hamasuna, Ryoichi; Yasuda, Mitsuru; Ishikawa, Kiyohito; Uehara, Shinya; Takahashi, Satoshi; Hayami, Hiroshi; Yamamoto, Shingo; Matsumoto, Tetsuro; Minamitani, Shinichi; Watanabe, Akira; Iwamoto, Aikichi; Totsuka, Kyoichi; Kadota, Junichi; Sunakawa, Keisuke; Sato, Junko; Hanaki, Hideaki; Tsukamoto, Taiji; Kiyota, Hiroshi; Egawa, Shin; Tanaka, Kazushi; Arakawa, Soichi; Fujisawa, Masato; Kumon, Hiromi; Kobayashi, Kanao; Matsubara, Akio; Naito, Seiji; Tatsugami, Katsunori; Ito, Shin; Narita, Harunori; Kanokogi, Mototsugu; Sumii, Toru; Ito, Kenji; Hosobe, Takahide; Kawai, Shuichi; Kawano, Hiromi; Takayama, Kazuo; Yamaguchi, Takamasa; Endo, Katsuhisa; Yamauchi, Takamine; Maeda, Shinichi; Yoh, Mutsumasa; Horie, Masanobu; Ito, Masayasu; Chokyu, Hirofumi; Ihara, Hideari; Akiyama, Kikuo; Uno, Satoshi; Monden, Koichi; Kaji, Shinichi; Nishimura, Hirofumi; Kawahara, Motoshi; Sato, Takashi; Konishi, Takatoshi; Nishi, Shohei; Ishihara, Satoshi; Yoshioka, Masaru

2013-08-01

Neisseria gonorrhoeae is one of the most important pathogens causing sexually transmitted infection, and strains that are resistant to several antimicrobials are increasing. To investigate the trends of antimicrobial susceptibility among N. gonorrhoeae strains isolated from male patients with urethritis, a Japanese surveillance committee conducted the first nationwide surveillance. The urethral discharge was collected from male patients with urethritis at 51 medical facilities from April 2009 to October 2010. Of the 156 specimens, 83 N. gonorrhoeae strains were tested for susceptibility to 18 antimicrobial agents. The prevalence of β-lactamase-producing strains and chromosomally mediated resistant strains were 7.2 % and 16.5 %, respectively. None of the strains was resistant to ceftriaxone, but the minimum inhibitory concentration (MIC) of ceftriaxone for 7 strains (8.4 %) was 0.125 μg/ml. One strain was resistant to cefixime (MIC 0.5 μg/ml). The MICs of fluoroquinolones, such as ciprofloxacin, levofloxacin, and tosufloxacin, showed a bimodal distribution. The MIC of sitafloxacin was lower than those of the three fluoroquinolones listed here, and it was found that the antimicrobial activity of sitafloxacin was stronger than that of the fluoroquinolones. The MIC of azithromycin in 2 strains was 2 μg/ml, but no high-level resistance to macrolides was detected.

Rhamnolipids from non-pathogenic Burkholderia thailandensis E264: Physicochemical characterization, antimicrobial and antibiofilm efficacy against oral hygiene related pathogens.

Science.gov (United States)

Elshikh, Mohamed; Funston, Scott; Chebbi, Alif; Ahmed, Syed; Marchant, Roger; Banat, Ibrahim M

2017-05-25

Biosurfactants are naturally occurring surface active compounds that have mainly been exploited for environmental applications and consumer products, with their biomedical efficacy an emerging area of research. Rhamnolipids area major group of biosurfactants that have been reported for their antimicrobial and antibiofilm efficacy. One of the main limiting factors for scaled up production and downstream applications of rhamnolipids is the fact that they are predominantly produced from the opportunistic pathogen Pseudomonas aeruginosa. In this article, we have reported the production and characterisation of long chain rhamnolipids from non-pathogenic Burkholderia thailandensis E264 (ATCC 700388). We have also investigated the antibacterial and antibiofilm properties of these rhamnolipids against some oral pathogens (Streptococcus oralis, Actinomyces naeslundii, Neisseria mucosa and Streptococcus sanguinis), important for oral health and hygiene. Treating these bacteria with different concentrations of long chain rhamnolipids resulted in a reduction of 3-4 log of bacterial viability, placing these rhamnolipids close to being classified as biocidal. Investigating long chain rhamnolipid efficacy as antibiofilm agents for prospective oral-related applications revealed good potency against oral-bacteria biofilms in a co-incubation experiments, in a pre-coated surface format, in disrupting immature biofilms and has shown excellent combination effect with Lauryl Sodium Sulphate which resulted in a drastic decrease in its minimal inhibitory concentration against different bacteria. Investigating the rhamnolipid permeabilization effect along with their ability to induce the formation of reactive oxygen species has shed light on the mechanism through which inhibition/killing of bacteria may occur. Copyright © 2017 Elsevier B.V. All rights reserved.

Epidemiology and outcomes of bacterial meningitis in Mexican children: 10-year experience (1993-2003).

Science.gov (United States)

Franco-Paredes, Carlos; Lammoglia, Lorena; Hernández, Isabel; Santos-Preciado, José Ignacio

2008-07-01

Acute bacterial meningitis remains an important cause of morbidity, neurologic sequelae, and mortality in children in Latin America. We retrospectively reviewed the hospital-based medical records of children diagnosed with acute bacterial meningitis, aged 1 month to 18 years, at a large inner city referral Hospital in Mexico City, for a 10-year period (1993-2003). To characterize the epidemiology, clinical features, and outcomes of acute bacterial meningitis, we subdivided our study into two time periods: the period prior to the routine use of Haemophilus influenzae type b (Hib) vaccine (1993-1998) and the period after the vaccine became available (1999-2003). A total of 218 cases of acute bacterial meningitis were identified during the study period. The most frequently affected age group was that of children aged between 1 and 6 months. Hib was the most commonly isolated pathogen, found in 50% of cases. However, its incidence declined significantly after the introduction of the combined diphtheria, tetanus, pertussis, hepatitis B, and conjugated Hib (DTP-HB/Hib) pentavalent vaccine into the universal vaccination schedule for children in 1998. Streptococcus pneumoniae followed as the second most commonly isolated bacterial pathogen. Neisseria meningitidis was isolated in only a few cases, confirming the historically low incidence of this pathogen in Mexico. Identified risk factors for death were found to include the presence of septic shock and intracranial hypertension, but were not attributable to any particular bacterial pathogen. In our hospital, acute bacterial meningitis remains a severe disease with important sequelae and mortality. The incidence of Hib meningitis cases has declined since the introduction of the Hib vaccine. However, S. pneumoniae persists as an important cause of bacterial meningitis, highlighting the need for the implementation of vaccination policies against this pathogen.

Lactobacillus paracasei feeding improves the control of secondary experimental meningococcal infection in flu-infected mice.

Science.gov (United States)

Belkacem, Nouria; Bourdet-Sicard, Raphaëlle; Taha, Muhamed-Kkeir

2018-04-10

The use of probiotics to improve anti-microbial defence, such as for influenza infections, is increasingly recommended. However, no data are available on the effect of probiotics on flu-associated secondary bacterial infections. There is strong evidence of a spatiotemporal association between influenza virus infection and invasive Neisseria meningitidis. We thus investigated the effect of feeding mice Lactobacillus paracasei CNCM I-1518 in a mouse model of sequential influenza-meningococcal infection. We intranasally infected BALB/c mice with a strain of influenza A virus (IAV) H3N2 that was first adapted to mice. Seven days later, a secondary bacterial infection was induced by intranasal administration of bioluminescent N. meningitidis. During the experiment, mice orally received either L. paracasei CNCM I-1518 or PBS as a control. The effect of L. paracasei administration on secondary bacterial infection by N. meningitidis was evaluated. Oral consumption of L. paracasei CNCM I-1518 reduced the weight loss of infected mice and lowered the bioluminescent signal of infecting meningococci. This improvement was associated with higher recruitment of inflammatory myeloid cells, such as interstitial monocytes and dendritic cells, to the lungs. Our data highlight the role of the gut-lung axis. L. paracasei CNCM I-1518 may boost the defence against IAV infection and secondary bacterial infection, which should be further studied and validated in clinical trials.

Neisseria meningitidis iron-regulated protein FrpD: crystallization and crystallographic characterization

Czech Academy of Sciences Publication Activity Database

Sviridova, E.; Bumba, Ladislav; Řezáčová, Pavlína; Procházková, Kateřina; Šebo, Peter; Kutá-Smatanová, Ivana

2011-01-01

Roč. 18, č. 1 (2011), s. 66-66 ISSN 1211-5894. [Discussions in Structural Molecular Biology /9./. 24.03.2011-26.03.2011, Nové Hrady] R&D Projects: GA MŠk(CZ) LC06010; GA ČR(CZ) GAP207/11/0717 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510; CEZ:AV0Z50520514 Keywords : proteins structure * meningitis * Xray crystalography Subject RIV: EB - Genetics ; Molecular Biology

Peptide Selectivity of the Proton-Coupled Oligopeptide Transporter from Neisseria meningitidis

DEFF Research Database (Denmark)

Sharma, Neha; Aduri, Nanda G; Iqbal, Anna

2016-01-01

POT). It has been shown that the gene encoding this transporter is upregulated during infection. NmPOT conformed to the typical chain length preference as observed in prototypical transporters of this family. In contrast to prototypical transporters, it was unable to accommodate a positively charged peptide...

Naturally Occurring Off-Switches for CRISPR-Cas9.

Science.gov (United States)

Pawluk, April; Amrani, Nadia; Zhang, Yan; Garcia, Bianca; Hidalgo-Reyes, Yurima; Lee, Jooyoung; Edraki, Alireza; Shah, Megha; Sontheimer, Erik J; Maxwell, Karen L; Davidson, Alan R

2016-12-15

CRISPR-Cas9 technology would be enhanced by the ability to inhibit Cas9 function spatially, temporally, or conditionally. Previously, we discovered small proteins encoded by bacteriophages that inhibit the CRISPR-Cas systems of their host bacteria. These "anti-CRISPRs" were specific to type I CRISPR-Cas systems that do not employ the Cas9 protein. We posited that nature would also yield Cas9 inhibitors in response to the evolutionary arms race between bacteriophages and their hosts. Here, we report the discovery of three distinct families of anti-CRISPRs that specifically inhibit the CRISPR-Cas9 system of Neisseria meningitidis. We show that these proteins bind directly to N. meningitidis Cas9 (NmeCas9) and can be used as potent inhibitors of genome editing by this system in human cells. These anti-CRISPR proteins now enable "off-switches" for CRISPR-Cas9 activity and provide a genetically encodable means to inhibit CRISPR-Cas9 genome editing in eukaryotes. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

Definition of a virulence-related antigen of Neisseria gonorrhoeae with monoclonal antibodies and lectins.

Science.gov (United States)

Demarco de Hormaeche, R; Bundell, C; Chong, H; Taylor, D W; Wildy, P

1986-03-01

Variants of one strain of Neisseria gonorrhoeae, grown in vivo or in vitro, that have been previously shown to differ in infectivity, serum resistance, and capsule production were compared with use of monoclonal antibodies and lectins. Monoclonal antibodies to virulent gonococci recognized an antigenic site of the lipopolysaccharide (LPS) produced in large amounts by gonococci grown in vivo but present only in a small proportion of in vitro-grown gonococci. This antigen (C-LPS) was found in all 85 different gonococcal isolates studied but not among nonpathogenic neisseriae. It was shared by group B and C meningococci but not by groups A and D. Enzyme-linked immunosorbent assay and Western blot analysis showed that N-acetylglucosamine and N-acetylgalactosamine form part of the epitope. The C-LPS antigen was shown by immunofluorescence to be present on the surface of the gonococci and also free as slime. This antigen appears to confer resistance to killing by normal sera.

Hearing impairment after childhood bacterial meningitis dependent on etiology in Luanda, Angola.

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Karppinen, Mariia; Pelkonen, Tuula; Roine, Irmeli; Cruzeiro, Manuel Leite; Peltola, Heikki; Pitkäranta, Anne

2015-11-01

Childhood bacterial meningitis (BM) damages hearing, but the potential of different agents to cause impairment in developing countries is poorly understood. We compared the extent of hearing impairment in BM caused by Haemophilus influenzae type b (Hib), Streptococcus pneumoniae or Neisseria meningitidis among children aged 2 months to 13 years in Luanda, Angola. Hearing of 685 ears of 351 (78%) survivors among 723 enrolled patients was tested by brainstem-evoked response audiometry on day 7 of hospitalization. The causative agent was sought by cerebrospinal fluid culture, PCR or the latex-agglutination test. Altogether, 45 (12%) of the survivors were deaf (threshold >80 dB), and 20 (6%) had a threshold of 80 dB. The incidence of any kind of hearing loss, with ≥60 dB, was 34% with Hib, 30% with S. pneumoniae, 19% with N. meningitidis and 33% with other bacteria. Examining all ears combined and using the ≥60 dB threshold, the agents showed dissimilar harm (P=0.005), Hib being the most frequent and N. meningitidis the most infrequent cause. Compared to other agents, S. pneumoniae more often caused deafness (P=0.025) and hearing impairment at ≥60 dB (P=0.017) in infants, whereas this level of hearing loss in older survivors was most commonly caused by Hib (P=0.031). BM among children in Angola is often followed by hearing impairment, but the risk depends on the agent. S. pneumoniae is a major problem among infants, whereas Hib is mainly a risk beyond 12 months. N. meningitidis impairs hearing less frequently. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Antimicrobial susceptibility profile of Neisseria gonorrhoeae at STI clinic

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Shilpee C

2008-01-01

Full Text Available A total of 100 consecutive patients who attended a sexually transmitted infections clinic were studied. Thirteen had gonococcal urethritis, of which 10 showed growth of Neisseria gonorrhoeae on culture. All the isolates were tested for antimicrobial susceptibility by Australian Gonococcal Surveillance Programme (AGSP method and beta lactamase production by chromogenic cephalosporin test. Four patients were co-infected with each of the following: HIV, HBV and Chlamydia trachomatis . Gonococcal urethritis (13% was found more in male patients. Ten percent gonococcal isolates were penicillinase-producing N. gonorrhoeae , and another 10% were tetracycline-resistant N. gonorrhoeae .

Dialects of the DNA Uptake Sequence in Neisseriaceae

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Frye, Stephan A.; Nilsen, Mariann; Tønjum, Tone; Ambur, Ole Herman

2013-01-01

In all sexual organisms, adaptations exist that secure the safe reassortment of homologous alleles and prevent the intrusion of potentially hazardous alien DNA. Some bacteria engage in a simple form of sex known as transformation. In the human pathogen Neisseria meningitidis and in related bacterial species, transformation by exogenous DNA is regulated by the presence of a specific DNA Uptake Sequence (DUS), which is present in thousands of copies in the respective genomes. DUS affects transformation by limiting DNA uptake and recombination in favour of homologous DNA. The specific mechanisms of DUS–dependent genetic transformation have remained elusive. Bioinformatic analyses of family Neisseriaceae genomes reveal eight distinct variants of DUS. These variants are here termed DUS dialects, and their effect on interspecies commutation is demonstrated. Each of the DUS dialects is remarkably conserved within each species and is distributed consistent with a robust Neisseriaceae phylogeny based on core genome sequences. The impact of individual single nucleotide transversions in DUS on meningococcal transformation and on DNA binding and uptake is analysed. The results show that a DUS core 5′-CTG-3′ is required for transformation and that transversions in this core reduce DNA uptake more than two orders of magnitude although the level of DNA binding remains less affected. Distinct DUS dialects are efficient barriers to interspecies recombination in N. meningitidis, N. elongata, Kingella denitrificans, and Eikenella corrodens, despite the presence of the core sequence. The degree of similarity between the DUS dialect of the recipient species and the donor DNA directly correlates with the level of transformation and DNA binding and uptake. Finally, DUS–dependent transformation is documented in the genera Eikenella and Kingella for the first time. The results presented here advance our understanding of the function and evolution of DUS and genetic transformation

The First World War years of Sydney Domville Rowland: an early case of possible laboratory-acquired meningococcal disease.

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Wever, Peter C; Hodges, A J

2016-08-01

Sydney Domville Rowland was a bacteriologist and staff member at the Lister Institute of Preventive Medicine when the First World War broke out in 1914. Following a request to the Director of the Lister Institute to staff and equip a mobile field laboratory as quickly as possible, Rowland was appointed to take charge of No. 1 Mobile Laboratory and took up a temporary commission at the rank of Lieutenant in the Royal Army Medical Corps. On 9 October 1914, Rowland set out for the European mainland and was subsequently attached to General Headquarters in Saint-Omer, France (October 1914-June 1915), No. 10 Casualty Clearing Station in Lijssenthoek, Belgium (June 1915-February 1916, during which period he was promoted Major), and No. 26 General Hospital in Étaples, France (February 1916-March 1917). His research focused on gas gangrene, typhoid fever, trench fever, wound infection and cerebrospinal fever. In February of 1917, while engaged in identifying meningococcal carriers, Rowland contracted cerebrospinal meningitis to which he succumbed at age 44 on 6 March 1917. His untimely death might have been caused by laboratory-acquired meningococcal disease, especially since Rowland's work with Neisseria meningitidis isolates had extended beyond routine laboratory techniques and included risk procedures like immunisation of rabbits with pathogenic strains isolated from cerebrospinal fluid. Currently, microbiology laboratory workers who are routinely exposed to N. meningitidis isolates are recognised as a population at increased risk for meningococcal disease, for which reason recommended preventive measures include vaccination and handling of isolates within a class II biosafety cabinet. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Dialects of the DNA uptake sequence in Neisseriaceae.

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Stephan A Frye

2013-04-01

Full Text Available In all sexual organisms, adaptations exist that secure the safe reassortment of homologous alleles and prevent the intrusion of potentially hazardous alien DNA. Some bacteria engage in a simple form of sex known as transformation. In the human pathogen Neisseria meningitidis and in related bacterial species, transformation by exogenous DNA is regulated by the presence of a specific DNA Uptake Sequence (DUS, which is present in thousands of copies in the respective genomes. DUS affects transformation by limiting DNA uptake and recombination in favour of homologous DNA. The specific mechanisms of DUS-dependent genetic transformation have remained elusive. Bioinformatic analyses of family Neisseriaceae genomes reveal eight distinct variants of DUS. These variants are here termed DUS dialects, and their effect on interspecies commutation is demonstrated. Each of the DUS dialects is remarkably conserved within each species and is distributed consistent with a robust Neisseriaceae phylogeny based on core genome sequences. The impact of individual single nucleotide transversions in DUS on meningococcal transformation and on DNA binding and uptake is analysed. The results show that a DUS core 5'-CTG-3' is required for transformation and that transversions in this core reduce DNA uptake more than two orders of magnitude although the level of DNA binding remains less affected. Distinct DUS dialects are efficient barriers to interspecies recombination in N. meningitidis, N. elongata, Kingella denitrificans, and Eikenella corrodens, despite the presence of the core sequence. The degree of similarity between the DUS dialect of the recipient species and the donor DNA directly correlates with the level of transformation and DNA binding and uptake. Finally, DUS-dependent transformation is documented in the genera Eikenella and Kingella for the first time. The results presented here advance our understanding of the function and evolution of DUS and genetic

The Meningitis Vaccine Project.

Science.gov (United States)

LaForce, F Marc; Konde, Kader; Viviani, Simonetta; Préziosi, Marie-Pierre

2007-09-03

Epidemic meningococcal meningitis is an important public health problem in sub-Saharan Africa. Current control measures rely on reactive immunizations with polysaccharide (PS) vaccines that do not induce herd immunity and are of limited effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate vaccines are effective in infants and have consistently shown an important effect on decreasing carriage, two characteristics that facilitate disease control. In 2001 the Meningitis Vaccine Project (MVP) was created as a partnership between PATH and the World Health Organization (WHO) with the goal of eliminating meningococcal epidemics in Africa through the development, licensure, introduction, and widespread use of conjugate meningococcal vaccines. Since group A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose) meningococcal A (Men A) conjugate vaccine through an innovative international partnership that saw transfer of a conjugation and fermentation technology to a developing country vaccine manufacturer. A Phase 1 study of the vaccine in India has shown that the product is safe and immunogenic. Phase 2 studies have begun in Africa, and a large demonstration study of the conjugate vaccine is envisioned for 2008-2009. After extensive consultations with African public health officials a vaccine introduction plan has been developed that includes introduction of the Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI) schedules but also emphasizes mass vaccination of 1-29 years old to induce herd immunity, a strategy that has been shown to be highly effective when the meningococcal C (Men C) conjugate vaccine was introduced in several European countries. The MVP model is a clear example of the usefulness of a "push mechanism" to finance the development of a needed vaccine for the developing world.

Prevention of Ophthalmia Neonatorum Caused by Neisseria gonorrhoeae Using a Fatty Acid-Based Formulation

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Colin P. Churchward

2017-07-01

Full Text Available Ophthalmia neonatorum, also called neonatal conjunctivitis, acquired during delivery can occur in the first 28 days of life. Commonly caused by the bacterial pathogen Neisseria gonorrhoeae, infection can lead to corneal scarring, perforation of the eye, and blindness. One approach that can be taken to prevent the disease is the use of an ophthalmic prophylaxis, which kills the bacteria on the surface of the eye shortly after birth. Current prophylaxes are based on antibiotic ointments. However, N. gonorrhoeae is resistant to many antibiotics and alternative treatments must be developed before the condition becomes untreatable. This study focused on developing a fatty acid-based prophylaxis. For this, 37 fatty acids or fatty acid derivatives were screened in vitro for fast antigonococcal activity. Seven candidates were identified as bactericidal at 1 mM. These seven were subjected to irritation testing using three separate methods: the bovine corneal opacity and permeability (BCOP test; the hen’s egg test—chorioallantoic membrane (HET-CAM; and the red blood cell (RBC lysis assay. The candidates were also tested in artificial tear fluid to determine whether they were effective in this environment. Four of the candidates remained effective. Among these, two lead candidates, monocaprin and myristoleic acid, displayed the best potential as active compounds in the development of a fatty acid-based prophylaxis for prevention of ophthalmia neonatorum.

Reproducibility Problems with the Abbott Laboratories LCx Assay for Chlamydia trachomatis and Neisseria gonorrhoeae

OpenAIRE

Gronowski, Ann M.; Copper, Susan; Baorto, David; Murray, Patrick R.

2000-01-01

This study demonstrates that significant reproducibility problems can occur during routine use of the Abbott Laboratories LCx assay for Chlamydia trachomatis and Neisseria gonorrhoeae. These problems can go undetected by the quality control procedures outlined in the manufacturer's package insert. We outline here procedures for detecting and preventing contamination and reproducibility problems.

Scale up of proteoliposome derived Cochleate production.

Science.gov (United States)

Zayas, Caridad; Bracho, Gustavo; Lastre, Miriam; González, Domingo; Gil, Danay; Acevedo, Reinaldo; del Campo, Judith; Taboada, Carlos; Solís, Rosa L; Barberá, Ramón; Pérez, Oliver

2006-04-12

Cochleate are highly stable structures with promising immunological features. Cochleate structures are usually obtaining from commercial lipids. Proteoliposome derived Cochleate are derived from an outer membrane vesicles of Neisseria meningitidis B. Previously, we obtained Cochleates using dialysis procedures. In order to increase the production process, we used a crossflow system (CFS) that allows easy scale up to obtain large batches in an aseptic environment. The raw material and solutions used in the production process are already approved for human application. This work demonstrates that CFS is very efficient process to obtain Cochleate structures with a yield of more than 80% and the immunogenicity comparable to that obtained by dialysis membrane.

Diagnostic value of polymerase chain reaction analysis of skin biopsies in purpura fulminans.

Science.gov (United States)

Beau, Caroline; Vlassova, Natalia; Sarlangue, Jean; Brissaud, Olivier; Léauté-Labrèze, Christine; Boralevi, Franck

2013-01-01

Even though prompt diagnosis and treatment of purpura fulminans (PF) is essential to reduce mortality, early administration of antibiotics may preclude identification of the causative agent by standard bacterial cultures and thus render definitive diagnosis impossible. Here we present a case of an infant with PF and negative bacterial cultures for whom polymerase chain reaction (PCR) analysis of a cutaneous biopsy specimen obtained 4 days after initiation of antibiotics identified the genomic sequence of Neisseria meningitidis genogroup C. When bacterial cultures fail to provide useful information, PCR of skin biopsy specimens can be a valuable diagnostic tool in PF. © 2013 Wiley Periodicals, Inc.

Prevalence and antimicrobial resistance pattern of bacterial meningitis in Egypt

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Shaban Lamyaa

2009-09-01

Full Text Available Abstract Infectious diseases are the leading cause of morbidity and mortality in the developing world. In Egypt bacterial diseases constitute a great burden, with several particular bacteria sustaining the leading role of multiple serious infections. This article addresses profound bacterial agents causing a wide array of infections including but not limited to pneumonia and meningitis. The epidemiology of such infectious diseases and the prevalence of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae are reviewed in the context of bacterial meningitis. We address prevalent serotypes in Egypt, antimicrobial resistance patterns and efficacy of vaccines to emphasize the importance of periodic surveillance for appropriate preventive and treatment strategies.

Dicty_cDB: Contig-U05052-1 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available oenzyme Q10 homolog B ... 77 4e-13 FM992692_323( FM992692 |pid:none) Candida dubliniensis CD36 chromo... 77 ...E017345 |pid:none) Cryptococcus neoformans var. neo... 64 4e-09 AM920433_567( AM920433 |pid:none) Penicillium chrysogenum Wisconsi... |pid:none) Neisseria meningitidis serogroup... 35 1.7 FM992694_108( FM992694 |pid:none) Candida dublinie...nsis CD36 chromo... 35 1.7 CT005255_117( CT005255 |pid:none) Leishmania major strain Fried...1266( CP000606 |pid:none) Shewanella loihica PV-4, comple... 49 1e-04 AP006725_3810( AP006725 |pid:none) Klebsiella pneumoni

History of meningococcal vaccines and their serological correlates of protection.

Science.gov (United States)

Vipond, Caroline; Care, Rory; Feavers, Ian M

2012-05-30

For over a hundred years Neisseria meningitidis has been known to be one of the major causes of bacterial meningitis. However, effective vaccines were not developed until the latter part of the 20th century. The first of these were based on purified high molecular weight capsular polysaccharides and more recently the development of glycoconjugate vaccines has made paediatric immunisation programmes possible. The prevention of group B meningococcal disease has remained a challenge throughout this period. This review charts the history of the development of meningococcal vaccines and the importance of serological correlates of protection in their evaluation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Distinct Neisseria gonorrhoeae Transmission Networks Among Men Who Have Sex With Men in Amsterdam, the Netherlands

NARCIS (Netherlands)

Heymans, Raymond; A Matser, Amy; Bruisten, Sylvia M.; Heijman, Titia; Geskus, Ronald B.; Speksnijder, Adrianus G. C. L.; Davidovich, Udi; de Vries, Henry J. C.; Coutinho, Roel A.; Schim van der Loeff, Maarten F.

2012-01-01

Background. Molecular typing was used to elucidate Neisseria gonorrhoeae transmission networks among men who have sex with men (MSM) in Amsterdam, the Netherlands. We determined whether clusters of patients infected with specific N. gonorrhoeae genotypes were related to various epidemiological

Infective endocarditis caused by Neisseria elongata on a native tricuspid valve and confirmed by DNA sequencing.

Science.gov (United States)

Yoo, Yeon Pyo; Kang, Ki-Woon; Yoon, Hyeon Soo; Yoo, Seungmin; Lee, Myung-Shin

2014-04-01

Neisseria elongata, a common oral bacterium, has been recognized as a cause of infections such as infective endocarditis, septicemia, and osteomyelitis. Neisseria-induced infective endocarditis, although infrequently reported, typically arises after dental procedures. Without antibiotic therapy, its complications can be severe. We report the case of a 27-year-old man who presented with fever, severe dyspnea, and a leg abscess from cellulitis. An echocardiogram showed a vegetation-like echogenic structure on the septal leaflet of the patient's native tricuspid valve, and an insignificant Gerbode defect. Three blood cultures grew gram-negative, antibiotic-susceptible coccobacilli that were confirmed to be N. elongata. Subsequent DNA sequencing conclusively isolated N. elongata subsp nitroreducens as the organism responsible for the infective endocarditis. The patient recovered after 21 days of antibiotic therapy. In addition to the patient's unusual case, we discuss the nature and isolation of N. elongata and its subspecies.

Divergent effects of Tenofovir and Retrovir (AZT) on TLR-mediated cytokine production

DEFF Research Database (Denmark)

Melchjorsen, Jesper; Tolstrup, Martin; Paludan, Søren Riis

  Pathogen-recognizing Toll-like receptors 2 (TLR2) and TLR4 are known to recognize a number of pathogens, including E.Coli, S. Pneumoniae and N. Meningitidis. We have studied whether a number of HIV therapeutics affect immediate proinflammatory cytokine responses in cell cultures. Preliminary...

The clinical presentation of acute bacterial meningitis varies with age, sex and duration of illness.

Science.gov (United States)

Johansson Kostenniemi, Urban; Norman, David; Borgström, Malin; Silfverdal, Sven Arne

2015-11-01

This Swedish study reviewed differences in clinical presentation and laboratory findings of acute bacterial meningitis in children aged one month to 17 years in Västerbotten County, Sweden. A register-based study was performed for the period 1986 to 2013 using the Västerbotten County Council's patient registration and laboratory records at the Department of Laboratory Medicine at Umeå University Hospital. The medical records were reviewed to extract data and confirm the diagnosis. We found 103 cases of acute bacterial meningitis, and Haemophilus influenzae was the most common pathogen, causing 40.8% of all cases, followed by Streptococcus pneumoniae at 30.1% and Neisseria meningitidis at 9.7%. Significant differences in clinical presentation and laboratory findings were found. Younger children were more unwell than older ones and had more diffuse symptoms on admission. In addition, important sex-related differences were found that might explain the higher case fatality rates for boys than girls. For example, boys tended to have a higher disturbance in the blood-brain barrier, which is known to be a negative prognostic factor. This study showed that clinical presentation for acute bacterial meningitis varied with age and sex and, to a lesser extent, on the duration of the illness. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

The epidemiology of bacterial meningitis in Kosovo.

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Namani, Sadie A; Koci, Remzie A; Qehaja-Buçaj, Emine; Ajazaj-Berisha, Lindita; Mehmeti, Murat

2014-07-14

The purpose of this study was to present the epidemiologic features of bacterial meningitis in the developing country of Kosovo. Data were collected from active surveillance of bacterial meningitis cases treated at the University Clinical Center of Kosovo in the years 2000 (first post-war year) and 2010. Meningitis cases in 2000 compared with 2010 showed a 35.5% decline in incidence (from 4.8 to 3.1 cases per 100,000 population) and a decrease in the case fatality rate from 10% to 5%. In children, there was a lower mortality rate (5% versus 2%) and a lower incidence of neurological complications (13% versus 16%) as compared to adults (32% versus 10% and 16% versus 35%, respectively). Neisseria meningitidis was the most common pathogen of bacterial meningitis in both study periods. Bacterial meningitis was most prevalent in the pediatric population, and showed an increase in the median age, from three years in 2000 to seven years in 2010. A steady number of bacterial meningitis cases in adults throughout last decade (around 20 cases per year) was recorded. During the last decade, gradual changes have been observed in the epidemiology of bacterial meningitis that are unrelated to the introduction of new vaccines, but are partly due to the improvement of living conditions.

Structure of a Novel N-acetyl-L-citrulline Deacetylase from Xanthomonas campestris

Energy Technology Data Exchange (ETDEWEB)

Shi,D.; Yu, X.; Roth, L.; Tuchman, M.; Allewell, N.

2007-01-01

The structure of a novel acetylcitrulline deacetylase from the plant pathogen Xanthomonas campestris has been solved by multiple-wavelength anomalous dispersion (MAD) using crystals grown from selenomethionine-substituted protein and refined at 1.75 {angstrom} resolution. The asymmetric unit of the crystal contains one monomer consisting of two domains, a catalytic domain and a dimerization domain. The catalytic domain is able to bind a single Co(II) ion at the active site with no change in confirmation. the dimerization domain forms an interface between two monomers related by a crystallographic two-fold symmetry axis. The interface is maintained by hydrophobic interactions between helices and hydrogen bonding between two {beta} strands that form a continuous {beta} sheet across the dimer interface. Because the dimers are also related by two-fold crystallographic axes, they pack together across the crystal via the dimerization domain, suggesting that higher order oligomers may form in solution. The polypeptide fold of the monomer is similar to the fold of Pseudomonas sp. carboxypeptidase G2 and Neisseria meningitidis succinyl diaminopimelate desuccinylase. Structural comparison among these enzymes allowed modeling of substrate binding and suggests a possible catalytic mechanism, in which Glu130 functions as a bifunctional general acid-base catalyst and the metal ion polarizes the carbonyl of the acetyl group.

Polymicrobial infective endocarditis caused by Neisseria sicca and Haemophilus parainfluenzae

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Nikoloz Koshkelashvili

2016-01-01

Full Text Available Infective endocarditis is a common clinical problem in industrialized countries. Risk factors include abnormal cardiac valves, a history of endocarditis, intracardiac devices, prosthetic valves and intravenous drug use. We report a case of polymicrobial infective endocarditis in a 33 year-old female with a history chronic heroin use caused by Neisseria sicca and Haemophilus parainfluenzae. We believe the patient was exposed to these microbes by cleansing her skin with saliva prior to injection. Pairing a detailed history with the consideration of atypical agents is crucial in the proper diagnosis and management of endocarditis in patients with high-risk injection behaviors.

Two-partner secretion systems of Neisseria meningitidis associated with invasive clonal complexes

NARCIS (Netherlands)

van Ulsen, Peter; Rutten, Lucy; Feller, Moniek; Tommassen, Jan; van der Ende, Arie

2008-01-01

The two-partner secretion (TPS) pathway is widespread among gram-negative bacteria and facilitates the secretion of very large and often virulence-related proteins. TPS systems consist of a secreted TpsA protein and a TpsB protein involved in TpsA transport across the outer membrane. Sequenced

Neisseria meningitidis RTX proteins ate notr tguired for virulence in infant rats

Czech Academy of Sciences Publication Activity Database

Forman, Stanislav; Linhartová, Irena; Osička, Radim; Nassif, X.; Šebo, Peter; Pelicic, V.

2003-01-01

Roč. 71, č. 4 (2003), s. 2253-2257 ISSN 0019-9567 R&D Projects: GA AV ČR IPP1050128; GA ČR GA310/02/1448; GA MŠk ME 581 Institutional research plan: CEZ:AV0Z5020903 Keywords : rtx * cytotoxin Subject RIV: EE - Microbiology, Virology Impact factor: 3.875, year: 2003

Rapid Field Response to a Cluster of Illnesses and Deaths - Sinoe County, Liberia, April-May, 2017.

Science.gov (United States)

Doedeh, John; Frimpong, Joseph Asamoah; Yealue, Kwuakuan D M; Wilson, Himiede W; Konway, Youhn; Wiah, Samson Q; Doedeh, Vivian; Bao, Umaru; Seneh, George; Gorwor, Lawrence; Toe, Sylvester; Ghartey, Emmanuel; Larway, Lawrence; Gweh, Dedesco; Gonotee, Philemon; Paasewe, Thomas; Tamatai, George; Yarkeh, James; Smith, Samuel; Brima-Davis, Annette; Dauda, George; Monger, Thomas; Gornor-Pewu, Leleh W; Lombeh, Siafa; Naiene, Jeremias; Dovillie, Nathaniel; Korvayan, Mark; George, Geraldine; Kerwillain, Garrison; Jetoh, Ralph; Friesen, Suzanne; Kinkade, Carl; Katawera, Victoria; Amo-Addae, Maame; George, Roseline N; Gbanya, Miatta Z; Dokubo, E Kainne

2017-10-27

On April 25, 2017, the Sinoe County Health Team (CHT) notified the Liberia Ministry of Health (MoH) and the National Public Health Institute of Liberia of an unknown illness among 14 persons that resulted in eight deaths in Sinoe County. On April 26, the National Rapid Response Team and epidemiologists from CDC, the World Health Organization (WHO) and the African Field Epidemiology Network (AFENET) in Liberia were deployed to support the county-led response. Measures were immediately implemented to identify all cases, ascertain the cause of illness, and control the outbreak. Illness was associated with attendance at a funeral event, and laboratory testing confirmed Neisseria meningitidis in biologic specimens from cases. The 2014-2015 Ebola virus disease (Ebola) outbreak in West Africa devastated Liberia's already fragile health system, and it took many months for the country to mount an effective response to control the outbreak. Substantial efforts have been made to strengthen Liberia's health system to prevent, detect, and respond to health threats. The rapid and efficient field response to this outbreak of N. meningitidis resulted in implementation of appropriate steps to prevent a widespread outbreak and reflects improved public health and outbreak response capacity in Liberia.

Tetracycline resistance and TetM in oral anaerobic bacteria and Neisseria perflava-N. sicca.

OpenAIRE

Roberts, M C; Moncla, B J

1988-01-01

Tetracycline-resistant organisms isolated from six patients with periodontal disease included Bacteroides spp., Eubacterium spp., Fusobacterium nucleatum, Neisseria perflava-N. sicca, Peptostreptococcus anaerobius, Veillonella parvula, and facultative streptococci. All but the Bacteroides spp. and Eubacterium spp. hybridized with the TetM determinant. An additional 417 bacterial strains were screened, and 4% of both the oral streptococci and the Fusobacterium spp. hybridized with the TetM probe.

Deep sequencing-based analysis of the anaerobic stimulon in Neisseria gonorrhoeae

Directory of Open Access Journals (Sweden)

Clark Virginia L

2011-01-01

Full Text Available Abstract Background Maintenance of an anaerobic denitrification system in the obligate human pathogen, Neisseria gonorrhoeae, suggests that an anaerobic lifestyle may be important during the course of infection. Furthermore, mounting evidence suggests that reduction of host-produced nitric oxide has several immunomodulary effects on the host. However, at this point there have been no studies analyzing the complete gonococcal transcriptome response to anaerobiosis. Here we performed deep sequencing to compare the gonococcal transcriptomes of aerobically and anaerobically grown cells. Using the information derived from this sequencing, we discuss the implications of the robust transcriptional response to anaerobic growth. Results We determined that 198 chromosomal genes were differentially expressed (~10% of the genome in response to anaerobic conditions. We also observed a large induction of genes encoded within the cryptic plasmid, pJD1. Validation of RNA-seq data using translational-lacZ fusions or RT-PCR demonstrated the RNA-seq results to be very reproducible. Surprisingly, many genes of prophage origin were induced anaerobically, as well as several transcriptional regulators previously unknown to be involved in anaerobic growth. We also confirmed expression and regulation of a small RNA, likely a functional equivalent of fnrS in the Enterobacteriaceae family. We also determined that many genes found to be responsive to anaerobiosis have also been shown to be responsive to iron and/or oxidative stress. Conclusions Gonococci will be subject to many forms of environmental stress, including oxygen-limitation, during the course of infection. Here we determined that the anaerobic stimulon in gonococci was larger than previous studies would suggest. Many new targets for future research have been uncovered, and the results derived from this study may have helped to elucidate factors or mechanisms of virulence that may have otherwise been overlooked.

Proteomic study via a non-gel based approach of meningococcal outer membrane vesicle vaccine obtained from strain CU385: a road map for discovering new antigens.

Science.gov (United States)

Gil, Jeovanis; Betancourt, L Zaro H; Sardiñas, Gretel; Yero, Daniel; Niebla, Olivia; Delgado, Maité; García, Darien; Pajón, Rolando; Sánchez, Aniel; González, Luis J; Padrón, Gabriel; Campa, Concepción; Sotolongo, Franklin; Barberó, Ramón; Guillén, Gerardo; Herrera, Luis; Besada, Vladimir

2009-05-01

This work presents the results from a study of the protein composition of outer membrane vesicles from VA-MENGOC-BC (Finlay Institute, Cuba), an available vaccine against serogroup B Neisseria meningitidis. Proteins were identified by means of SCAPE, a 2DE-free method for proteome studies. More than one hundred proteins were detected by tandem liquid chromatographymass spectrometry analysis of fractions enriched in peptides devoid of histidine or arginine residues, providing a detailed description of the vaccine. A bioinformatic analysis of the identified components resulted in the identification of 31 outer membrane proteins and three conserved hypothetical proteins, allowing the cloning, expression, purification and immunological study of two of them (NMB0088 and NMB1796) as new antigens.

Chlamydia trachomatis and Neisseria gonorrhoeae in asymptomatic family planning patients in rural New Mexico.

OpenAIRE

Bell, T A; Ebenezer, M R

1989-01-01

We tested 98 asymptomatic women seen in state-funded contraception clinics in rural New Mexico. A fluorescein-conjugated monoclonal antibody stain revealed Chlamydia trachomatis infection in 25% of asymptomatic unmarried women and 3% of married women (P = .03). Neisseria gonorrhoeae was detected in only one woman. As in urban clinics providing contraception, the prevalence of gonorrhea is rare in rural New Mexico, but chlamydial infections are common in young unmarried women.

A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation From Immunogenicity

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David J. Dowling

2016-12-01

Full Text Available Background. Group B Neisseria meningitidis, an endotoxin-producing gram-negative bacterium, causes the highest incidence of group B meningococcus (MenB disease in the first year of life. The Bexsero vaccine is indicated in Europe from 8 weeks of age. Endotoxin components of outer membrane vesicles (OMVs or soluble lipopolysaccharide (LPS represent a potential source of inflammation and residual reactogenicity. The purpose of this study was to compare novel candidate MenB vaccine formulations with licensed vaccines, including Bexsero, using age-specific in vitro culture systems.Methods. OMVs from wild type and inactivated lpxL1 gene mutant N. meningitidis strains were characterized in human neonatal and adult in vitro whole blood assays and dendritic cell arrays. OMVs were benchmarked against licensed vaccines, including Bexsero and whole cell pertussis formulations, with respect to Th-polarizing cytokine and PGE2 production, as well as cell surface activation markers (HLA-DR, CD86, CCR7. OMV immunogenicity was assessed in mice.Results. ΔlpxLI native OMVs demonstrated significantly less cytokine induction in human blood and DCs than Bexsero and most of the other pediatric vaccines (e.g., PedvaxHib, EasyFive, Bacillus Calmette–Guérin (BCG tested. Despite a much lower inflammatory profile in vitro than Bexsero, ΔlpxLI native OMVs still had moderate DC maturing ability and induced robust anti-N. meningitidis antibody responses after murine immunization.Conclusions. A meningococcal vaccine comprised of attenuated LPS-based OMVs with a limited inflammatory profile in vitro induces robust antigen-specific immunogenicity in vivo.

Chlamydia trachomatis Serovar Distribution and Neisseria gonorrhoeae Coinfection in Male Patients with Urethritis in Greece▿

Science.gov (United States)

Papadogeorgakis, Helen; Pittaras, Theodore E.; Papaparaskevas, Joseph; Pitiriga, Vassiliki; Katsambas, Andreas; Tsakris, Athanassios

2010-01-01

The distribution of Chlamydia trachomatis serovars and Neisseria gonorrhoeae coinfection was studied in a group of 100 C. trachomatis-positive males with urethritis in Greece. The serovar distribution revealed that apart from the predominant worldwide types E and F, the relatively uncommon type G is also prevalent. Gonococcal coinfection was frequent (30%) and was associated with genovariant Ja (75%, P = 0.008). PMID:20357220

Distribution of pathogenic microorganisms isolated from dental hospital workers in Korea

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Su Jung Kim

2013-04-01

Full Text Available With the significant rise in hospital infection management in dental hospitals as well as in hospitals, and in order to identify the distribution of pathogenic bacteria on hands and nasal cavity of workers in a dental hospital, bacteria from the hands and nasal cavities of six dentists and 44 dental hygienists from four dental hospitals were investigated. The results showed Staphylococcus aureus (13, Staphylococcus capitis (1, Staphylococcus epidermidis (12, Staphylococcus hominis (4, Staphylococcus warneri (3, Staphylococcus xylosus (14, Staphylococcus. Lugdunensis (1, and Neisseria spp. (2 were isolated from the nasal cavity and Staphylococcus aureus (9, Staphylococcus capitis (4, Staphylococcus epidermidis (16, Staphylococcus hominis (8, Staphylococcus warneri (5, Staphylococcus xylosus (22, Staphylococcus leutus (3, Micrococcus spp. (4, Staphylococcus cohnii (1, Serratia marcescens (2, Pseudomonas aeruginosa (3, Klebsiella pneumonia (2 and Pseudomonas pneumotropica (1 from the hands. An antimicrobial disk diffusion test was conducted on Staphylococcus aureus isolated from the hands and nasal cavity to detect MRSA by means of oxacillin. Two strains were detected. When the genes of penicillin binding protein 2 (mecA were detected from the 2 strains, MRSA was found from both strains. The results of this investigation on the distribution of various pathogenic bacteria and MRSA on hands and nasal cavity of workers of a dental hospital, will contribute to the basic data for the future infection management in a dental hospital.

Urethritis/cervicitis pathogen prevalence and associated risk factors among asymptomatic HIV-infected patients in South Africa.

Science.gov (United States)

Lewis, David A; Chirwa, Tobias F; Msimang, Veerle M Y; Radebe, Frans M; Kamb, Mary L; Firnhaber, Cynthia S

2012-07-01

To determine sexually transmitted infection (STI) prevalence, and patient characteristics associated with detection of urethritis/cervicitis pathogens, among HIV-infected individuals offered voluntary STI screening at a South African HIV treatment center. Individuals, asymptomatic for genital discharge, were screened for Neisseria gonorrhoeae (NG), Chlamydia trachomatis, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) infections (real-time polymerase chain reaction assay), for syphilis and herpes simplex type 2 (serologically), and for bacterial vaginosis and Candida (microscopy, women only). Patients' most recent CD4 and viral load results were recorded. Demographic, clinical, and behavioral data were collected by nurse-administered questionnaire. Compared with men (n = 551), women (n = 558) were younger (mean age, 35.0 vs. 37.9 years; P urethritis/cervicitis pathogens detected (21.3% vs.16.4%, P = 0.035), and were less aware of their partner's HIV status (53.1% vs. 62.3%; P = 0.007). The overall prevalence of individual urethritis/cervicitis pathogens was TV (7.6%), MG (6.1%), NG (5.4%), and C. trachomatis (2.1%). Multivariate analysis highlighted 4 significant factors associated with the detection of specific urethritis/cervicitis pathogens, namely female gender (TV, adjusted odds ratio [aOR] 2.53, 95% confidence interval [CI]: 1.47-4.37), having a regular sexual partner in the past 3 months (NG, aOR 2.26, 95% CI: 1.01-5.08), suboptimal condom use with regular partners (TV, aOR 2.07, 95% CI: 1.25-3.42), and a history of genital warts in the past year (NG, 2.25, 95% CI: 1.26-4.03). Asymptomatic urethritis/cervicitis pathogens were highly prevalent in this population. Few urethritis/cervicitis pathogen-associated patient characteristics were identified, emphasizing the need for affordable STI diagnostics to screen HIV-infected patients.

Lipooligosaccharide structure is an important determinant in the resistance of Neisseria gonorrhoeae to antimicrobial agents of innate host defense

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Jacqueline T Balthazar

2011-02-01

Full Text Available The strict human pathogen Neisseria gonorrhoeae has caused the sexually transmitted infection termed gonorrhea for thousands of years. Over the millennia, the gonococcus has likely evolved mechanisms to evade host defense systems that operate on the genital mucosal surfaces in both males and females. Past research has shown that the presence or modification of certain cell envelope structures can significantly impact levels of gonococcal susceptibility to host-derived antimicrobial compounds that bathe genital mucosal surfaces and participate in innate host defense against invading pathogens. In order to facilitate the identification of gonococcal genes that are important in determining levels of bacterial susceptibility to mediators of innate host defense, we used the Himar I mariner in vitro mutagenesis system to construct a transposon insertion library in strain F62. As proof of principle that this strategy would be suitable for this purpose, we screened the library for mutants expressing decreased susceptibility to the bacteriolytic action of normal human serum (NHS. We found that a transposon insertion in the lgtD gene, which encodes an N-acetylgalactosamine transferase involved in the extension of the α-chain of lipooligosaccharide (LOS, could confer decreased susceptibility of strain F62 to complement-mediated killing by NHS. By complementation and chemical analyses, we demonstrated both linkage of the transposon insertion to the NHS-resistance phenotype and chemical changes in LOS structure that resulted from loss of LgtD production. Further truncation of the LOS α-chain or loss of phosphoethanolamine (PEA from the lipid A region of LOS also impacted levels of NHS-resistance. PEA decoration of lipid A also increased gonococcal resistance to the model cationic antimicrobial polymyxin B. Taken together, we conclude that the Himar I mariner in vitro mutagenesis procedure can facilitate studies on structures involved in gonococcal

Nanostructured platform for the detection of Neisseria gonorrhoeae using electrochemical impedance spectroscopy and differential pulse voltammetry

International Nuclear Information System (INIS)

Singh, R.; Matharu, Z.; Srivastava, A.K.; Sood, S.; Gupta, R.K.; Malhotra, B.D.

2012-01-01

We report on a nanocomposite based genosensor for the detection of Neisseria gonorrhoeae, a bacterium causing the sexually transmitted disease gonorrhoea. Amino-labeled probe DNA was covalently immobilized on electrochemically prepared polyaniline and iron oxide (PANI-Fe 3 O 4 ) nanocomposite film on an indium tin oxide (ITO) electrode. Scanning electron microscopy, transmission electron microscopy, electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) techniques have been employed to characterize surface of the modified electrode. The genosensor has detection limits of 1 x 10 -15 M and 1 x 10 -17 M, respectively, using the EIS and DPV techniques. This biosensor can discriminate a complementary sequence from a single-base mismatch and from non-complementary DNA, and has been utilized for detection of DNA extracted from N. gonorrhoeae culture, and from patient samples with N. gonorrhoeae. It is found to exhibit good specificity for N. gonorrhoeae species and shows no response towards non-gonorrhoeae type of Neisseria species (NgNs) and other gram-negative bacterias (GNBs). The affinity constant for hybridization calculated using the Langmuir adsorption isotherm model is found to be 3. 39 x 10 8 M -1 . (author)

Comparison of Neisseria gonorrhoeae MICs Obtained by Etest and Agar Dilution for Ceftriaxone, Cefpodoxime, Cefixime and Azithromycin.

Science.gov (United States)

Gose, Severin; Kong, Carol J; Lee, Yer; Samuel, Michael C; Bauer, Heidi M; Dixon, Paula; Soge, Olusegun O; Lei, John; Pandori, Mark

2013-10-24

We evaluated Neisseria gonorrhoeae Etest minimum inhibitory concentrations (MICs) relative to agar dilution MICs for 664 urethral isolates for ceftriaxone (CRO) and azithromycin (AZM), 351 isolates for cefpodoxime (CPD) and 315 isolates for cefixime (CFM). Etest accurately determined CPD, CFM and AZM MICs, but resulted in higher CRO MICs. © 2013. Published by Elsevier B.V. All rights reserved.

Effective plasmid DNA and small interfering RNA delivery to diseased human brain microvascular endothelial cells.

Science.gov (United States)

Slanina, H; Schmutzler, M; Christodoulides, M; Kim, K S; Schubert-Unkmeir, A

2012-01-01

Expression of exogenous DNA or small interfering RNA (siRNA) in vitro is significantly affected by the particular delivery system utilized. In this study, we evaluated the transfection efficiency of plasmid DNA and siRNA into human brain microvascular endothelial cells (HBMEC) and meningioma cells, which constitute the blood-cerebrospinal fluid barrier, a target of meningitis-causing pathogens. Chemical transfection methods and various lipofection reagents including Lipofectamin™, FuGene™, or jetPRIME®, as well as physical transfection methods and electroporation techniques were applied. To monitor the transfection efficiencies, HBMEC and meningioma cells were transfected with the reporter plasmid pTagGFP2-actin vector, and efficiency of transfection was estimated by fluorescence microscopy and flow cytometry. We established protocols based on electroporation using Cell Line Nucleofector® Kit V with the Amaxa® Nucleofector® II system from Lonza and the Neon® Transfection system from Invitrogen resulting in up to 41 and 82% green fluorescent protein-positive HBMEC, respectively. Optimal transfection solutions, pulse programs and length were evaluated. We furthermore demonstrated that lipofection is an efficient method to transfect meningioma cells with a transfection efficiency of about 81%. Finally, we applied the successful electroporation protocols to deliver synthetic siRNA to HBMEC and analyzed the role of the actin-binding protein cortactin in Neisseria meningitidis pathogenesis. Copyright © 2012 S. Karger AG, Basel.

Enhancing the Biological Relevance of Machine Learning Classifiers for Reverse Vaccinology

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Ashley I. Heinson

2017-02-01

Full Text Available Reverse vaccinology (RV is a bioinformatics approach that can predict antigens with protective potential from the protein coding genomes of bacterial pathogens for subunit vaccine design. RV has become firmly established following the development of the BEXSERO® vaccine against Neisseria meningitidis serogroup B. RV studies have begun to incorporate machine learning (ML techniques to distinguish bacterial protective antigens (BPAs from non-BPAs. This research contributes significantly to the RV field by using permutation analysis to demonstrate that a signal for protective antigens can be curated from published data. Furthermore, the effects of the following on an ML approach to RV were also assessed: nested cross-validation, balancing selection of non-BPAs for subcellular localization, increasing the training data, and incorporating greater numbers of protein annotation tools for feature generation. These enhancements yielded a support vector machine (SVM classifier that could discriminate BPAs (n = 200 from non-BPAs (n = 200 with an area under the curve (AUC of 0.787. In addition, hierarchical clustering of BPAs revealed that intracellular BPAs clustered separately from extracellular BPAs. However, no immediate benefit was derived when training SVM classifiers on data sets exclusively containing intra- or extracellular BPAs. In conclusion, this work demonstrates that ML classifiers have great utility in RV approaches and will lead to new subunit vaccines in the future.

Enhancing the Biological Relevance of Machine Learning Classifiers for Reverse Vaccinology

KAUST Repository

Heinson, Ashley

2017-02-01

Reverse vaccinology (RV) is a bioinformatics approach that can predict antigens with protective potential from the protein coding genomes of bacterial pathogens for subunit vaccine design. RV has become firmly established following the development of the BEXSERO® vaccine against Neisseria meningitidis serogroup B. RV studies have begun to incorporate machine learning (ML) techniques to distinguish bacterial protective antigens (BPAs) from non-BPAs. This research contributes significantly to the RV field by using permutation analysis to demonstrate that a signal for protective antigens can be curated from published data. Furthermore, the effects of the following on an ML approach to RV were also assessed: nested cross-validation, balancing selection of non-BPAs for subcellular localization, increasing the training data, and incorporating greater numbers of protein annotation tools for feature generation. These enhancements yielded a support vector machine (SVM) classifier that could discriminate BPAs (n = 200) from non-BPAs (n = 200) with an area under the curve (AUC) of 0.787. In addition, hierarchical clustering of BPAs revealed that intracellular BPAs clustered separately from extracellular BPAs. However, no immediate benefit was derived when training SVM classifiers on data sets exclusively containing intra- or extracellular BPAs. In conclusion, this work demonstrates that ML classifiers have great utility in RV approaches and will lead to new subunit vaccines in the future.

Enhancing the Biological Relevance of Machine Learning Classifiers for Reverse Vaccinology

KAUST Repository

Heinson, Ashley; Gunawardana, Yawwani; Moesker, Bastiaan; Hume, Carmen; Vataga, Elena; Hall, Yper; Stylianou, Elena; McShane, Helen; Williams, Ann; Niranjan, Mahesan; Woelk, Christopher

2017-01-01

Reverse vaccinology (RV) is a bioinformatics approach that can predict antigens with protective potential from the protein coding genomes of bacterial pathogens for subunit vaccine design. RV has become firmly established following the development of the BEXSERO® vaccine against Neisseria meningitidis serogroup B. RV studies have begun to incorporate machine learning (ML) techniques to distinguish bacterial protective antigens (BPAs) from non-BPAs. This research contributes significantly to the RV field by using permutation analysis to demonstrate that a signal for protective antigens can be curated from published data. Furthermore, the effects of the following on an ML approach to RV were also assessed: nested cross-validation, balancing selection of non-BPAs for subcellular localization, increasing the training data, and incorporating greater numbers of protein annotation tools for feature generation. These enhancements yielded a support vector machine (SVM) classifier that could discriminate BPAs (n = 200) from non-BPAs (n = 200) with an area under the curve (AUC) of 0.787. In addition, hierarchical clustering of BPAs revealed that intracellular BPAs clustered separately from extracellular BPAs. However, no immediate benefit was derived when training SVM classifiers on data sets exclusively containing intra- or extracellular BPAs. In conclusion, this work demonstrates that ML classifiers have great utility in RV approaches and will lead to new subunit vaccines in the future.

Determination of recombination in Mycoplasma hominis

DEFF Research Database (Denmark)

Jacobsen, Iben Søgaard; Boesen, Thomas; Mygind, Tina

2002-01-01

disequilibrium and distance between the segregating sites, by the homoplasy ratio (H ratio), and by compatibility matrices. The gap gene showed well-supported evidence for high levels of recombination, whereas recombination was less frequent and not significant within the other genes. The analysis revealed......B-hitL, excinuclease ABC subunit A (uvrA) and glyceraldehyde-3-phosphate dehydrogenase (gap) genes. The level of variability of these M. hominis genes was low compared with the housekeeping genes from Helicobacter pylori and Neisseria meningitidis, but only few M. hominis isolates had identical sequences in all genes...... intergenic and intragenic recombination in M. hominis and this may explain the high intraspecies variability. The results obtained in the present study may be of importance for future population studies of Mycoplasma species....

Visualization of bacterial polysaccharides by scanning transmission electron microscopy.

Science.gov (United States)

Wolanski, B S; McAleer, W J; Hilleman, M R

1983-04-01

Highly purified capsular polysaccharides of Neisseria meningitidis groups A, B, and C have been visualized by high resolution Scanning Transmission Electron Microscopy (STEM). Spheroidal macromolecules approximately 200 A in diameter are characteristic of the Meningococcus A and C polysaccharides whereas filaments that are 400-600 A in length are found in Meningococcus B polysaccharide preparations. Filaments are occasionally found associated with the spheroidal Meningococcus A and C polysaccharides and it is proposed that these structures are composed of a long (1-4 microns) filament or filaments that are arranged in spheroidal molecules or micelles of high molecular weight. The Meningococcus B polysaccharide, by contrast, is a short flexuous filament or strand of relatively low molecular weight. A relationship between morphology and antigenicity is proposed.

Meningococcal Serogroup B Bivalent rLP2086 Vaccine Elicits Broad and Robust Serum Bactericidal Responses in Healthy Adolescents

DEFF Research Database (Denmark)

Vesikari, Timo; Østergaard, Lars Jørgen; Diez-Domingo, Javier

2015-01-01

BACKGROUND: Neisseria meningitidis serogroup B (MnB) is a leading cause of invasive meningococcal disease in adolescents and young adults. A recombinant factor H binding protein (fHBP) vaccine (Trumenba(®); bivalent rLP2086) was recently approved in the United States in individuals aged 10-25 years....... Immunogenicity and safety of 2- or 3-dose schedules of bivalent rLP2086 were assessed in adolescents. METHODS: Healthy adolescents (11 to ... bactericidal antibody assay using human complement (hSBA). Safety assessments included local and systemic reactions and adverse events. RESULTS: Bivalent rLP2086 was immunogenic when administered as 2 or 3 doses; the most robust hSBA responses occurred with 3 doses. The proportion of subjects with hSBA titers...

DprA from Neisseria meningitidis: properties and role in natural competence for transformation.

Science.gov (United States)

Hovland, Eirik; Beyene, Getachew Tesfaye; Frye, Stephan A; Homberset, Håvard; Balasingham, Seetha V; Gómez-Muñoz, Marta; Derrick, Jeremy P; Tønjum, Tone; Ambur, Ole H

2017-07-01

DNA processing chain A (DprA) is a DNA-binding protein that is ubiquitous in bacteria and expressed in some archaea. DprA is active in many bacterial species that are competent for transformation of DNA, but its role in Neisseriameningitidis (Nm) is not well characterized. An Nm mutant lacking DprA was constructed, and the phenotypes of the wild-type and ΔdprA mutant were compared. The salient feature of the phenotype of dprA null cells is the total lack of competence for genetic transformation shown by all of the donor DNA substrates tested in this study. Here, Nm wild-type and dprA null cells appeared to be equally resistant to genotoxic stress. The gene encoding DprANm was cloned and overexpressed, and the biological activities of DprANm were further investigated. DprANm binds ssDNA more strongly than dsDNA, but lacks DNA uptake sequence-specific DNA binding. DprANm dimerization and interaction with the C-terminal part of the single-stranded binding protein SSBNmwere demonstrated. dprA is co-expressed with smg, a downstream gene of unknown function, and the gene encoding topoisomerase 1, topA.

Involvement of three meningococcal surface-exposed proteins, the heparin-binding protein NhbA, the α-peptide of IgA protease and the autotransporter protease NalP, in initiation of biofilm formation

KAUST Repository

Arenas, Jesús

2012-12-04

Neisseria meningitidis is a common and usually harmless inhabitant of the mucosa of the human nasopharynx, which, in rare cases, can cross the epithelial barrier and cause meningitis and sepsis. Biofilm formation favours the colonization of the host and the subsequent carrier state. Two different strategies of biofilm formation, either dependent or independent on extracellular DNA (eDNA), have been described for meningococcal strains. Here, we demonstrate that the autotransporter protease NalP, the expression of which is phase variable, affects eDNA-dependent biofilm formation in N.meningitidis. The effect of NalP was found in biofilm formation under static and flow conditions and was dependent on its protease activity. Cleavage of the heparin-binding antigen NhbA and the α-peptide of IgA protease, resulting in the release of positively charged polypeptides from the cell surface, was responsible for the reduction in biofilm formation when NalP is expressed. Both NhbA and the α-peptide of IgA protease were shown to bind DNA. We conclude that NhbA and the α-peptide of IgA protease are implicated in biofilm formation by binding eDNA and that NalP is an important regulator of this process through the proteolysis of these surface-exposed proteins. © 2012 Blackwell Publishing Ltd.

Involvement of three meningococcal surface-exposed proteins, the heparin-binding protein NhbA, the α-peptide of IgA protease and the autotransporter protease NalP, in initiation of biofilm formation

KAUST Repository

Arenas, Jesú s; Nijland, Reindert; Rodriguez, Francisco J.; Bosma, Tom N. P.; Tommassen, Jan

2012-01-01

Neisseria meningitidis is a common and usually harmless inhabitant of the mucosa of the human nasopharynx, which, in rare cases, can cross the epithelial barrier and cause meningitis and sepsis. Biofilm formation favours the colonization of the host and the subsequent carrier state. Two different strategies of biofilm formation, either dependent or independent on extracellular DNA (eDNA), have been described for meningococcal strains. Here, we demonstrate that the autotransporter protease NalP, the expression of which is phase variable, affects eDNA-dependent biofilm formation in N.meningitidis. The effect of NalP was found in biofilm formation under static and flow conditions and was dependent on its protease activity. Cleavage of the heparin-binding antigen NhbA and the α-peptide of IgA protease, resulting in the release of positively charged polypeptides from the cell surface, was responsible for the reduction in biofilm formation when NalP is expressed. Both NhbA and the α-peptide of IgA protease were shown to bind DNA. We conclude that NhbA and the α-peptide of IgA protease are implicated in biofilm formation by binding eDNA and that NalP is an important regulator of this process through the proteolysis of these surface-exposed proteins. © 2012 Blackwell Publishing Ltd.

Cephalosporin resistance in Neisseria gonorrhoeae

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Manju Bala

2010-01-01

Full Text Available Gonorrhea, a disease of public health importance, not only leads to high incidence of acute infections and complications but also plays a major role in facilitating human immunodeficiency virus (HIV acquisition and transmission. One of the major public health needs for gonorrhea control is appropriate, effective treatment. However, treatment options for gonorrhea are diminishing as Neisseria gonorrhoeae have developed resistance to several antimicrobial drugs such as sulfonamides, penicillin, tetracyclines and quinolones. Antimicrobial resistance (AMR surveillance of N. gonorrhoeae helps establish and maintain the efficacy of standard treatment regimens. AMR surveillance should be continuous to reveal the emergence of new resistant strains, monitor the changing patterns of resistance, and be able to update treatment recommendations so as to assist in disease control. Current treatment guidelines recommend the use of single dose injectable or oral cephalosporins. The emergence and spread of cephalosporin resistant and multi drug resistant N. gonorrhoeae strains, represents a worrying trend that requires monitoring and investigation. Routine clinical laboratories need to be vigilant for the detection of such strains such that strategies for control and prevention could be reviewed and revised from time to time. It will be important to elucidate the genetic mechanisms responsible for decreased susceptibility and future resistance. There is also an urgent need for research of safe, alternative anti-gonococcal compounds that can be administered orally and have effective potency, allowing high therapeutic efficacy (greater than 95.0% cure rate.

Inmunización intranasal con AFCo1 induce respuesta inmune de memoria, sistemica y mucosal en ratones neonatal

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Julio A. Balboa

2009-08-01

Full Text Available Neonates have a poorly developed immune system. Respiratory pathogens cause disease during early periods of live. Consequently, it is important to develop protective vaccines that induce immunity and immunological memory against respiratory pathogens early in life. Intranasal (i.n. route could be an effective via for immunization. Therefore, we explored the effectiveness of AF (Adjuvant Finlay PL1 (Proteoliposome from Neisseria meningitidis serogroup B and its derivate Cochleate (AFCo1 by nasal route in neonatal mice. They were immunized i.n. 3 times 7 days apart and anti PL systemic and mucosal antibody response were measured by ELISA. In addition, a prime-boost strategy was used to evaluate the humoral immune response in neonate mice. The 3 doses of AFPL1 or AFCo1 induced significant levels of anti PL IgG antibodies in comparison whit control, but AFCo1 (2017 U/mL was significantly higher than AFPL1 (1107 U/mL. AFCo1 and AFPL1 induced a predominant Th1 pattern with IgG2a/IgG1 >1 by i.n. immunization and AFCo1 induced a high anti PL IgA saliva response in saliva. Interestingly, one nasally prime at 7 days of born and a memory one boost i.n. dose 9 weeks later with AFCo1 or AFPL1 showed similar specific IgG levels and IgG2a/IgG1 relation than 3 i.n. doses in adult mice. In conclusion, these results represent the first report of neonatal intranasal vaccination using AFCo1 capable to induce systemic and mucosal immunity and priming for memory.

Multiple strategies to improve sensitivity, speed and robustness of isothermal nucleic acid amplification for rapid pathogen detection

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Lemieux Bertrand

2011-05-01

Full Text Available Abstract Background In the past decades the rapid growth of molecular diagnostics (based on either traditional PCR or isothermal amplification technologies meet the demand for fast and accurate testing. Although isothermal amplification technologies have the advantages of low cost requirements for instruments, the further improvement on sensitivity, speed and robustness is a prerequisite for the applications in rapid pathogen detection, especially at point-of-care diagnostics. Here, we describe and explore several strategies to improve one of the isothermal technologies, helicase-dependent amplification (HDA. Results Multiple strategies were approached to improve the overall performance of the isothermal amplification: the restriction endonuclease-mediated DNA helicase homing, macromolecular crowding agents, and the optimization of reaction enzyme mix. The effect of combing all strategies was compared with that of the individual strategy. With all of above methods, we are able to detect 50 copies of Neisseria gonorrhoeae DNA in just 20 minutes of amplification using a nearly instrument-free detection platform (BESt™ cassette. Conclusions The strategies addressed in this proof-of-concept study are independent of expensive equipments, and are not limited to particular primers, targets or detection format. However, they make a large difference in assay performance. Some of them can be adjusted and applied to other formats of nucleic acid amplification. Furthermore, the strategies to improve the in vitro assays by maximally simulating the nature conditions may be useful in the general field of developing molecular assays. A new fast molecular assay for Neisseria gonorrhoeae has also been developed which has great potential to be used at point-of-care diagnostics.

SIGNIFICATIVE ANO PROBLEM BASED LEARNING IN IMMUNOLOGY: OBTAINING A KIT TO TYPE NEISSERIA GONORRHOEAE

Directory of Open Access Journals (Sweden)

Marina Miguez

2003-06-01

Full Text Available Neisseria gonorrhoeae (Ng have been classified serologically on the basis of the antigenicity of the major porin (Por. Por! occurs in two immunochemically distinct serogroups: PorlA and Porffi. Because the diagnostic, therapeutic, social, and legal corisequences of misidentification of a nongonococcal Neisseria isolate as Ng can be substantial, the accurate and rapid identification of this organism is important. Typifying of Ng is done by techniques baséd on phenotypic characteristics and plasmidic content that individually don't reach an adequate discrimination, and so combination of techniques ·must be used. The aim of this work is to obtain polyclonal specificAb that discriminate Ng types Por!Aand Porffi. For this purpose, weimmunized two rabbits with sonicated PorlA and Porm strains ofNg (isolated from clínica! samples and serologically classified. The Ab response was analyzed along the protocol by ELISAand by direct agglutination with latex coated with sonicated Ng. With these data, we selected the bleeding providing the serum with maximum specific Ab ti ter to prepare the typing reagents. Unwanted Ab directed against shared epitopes were removed by adsorption with Ng latex. The typing reagents were obtained by coating latex with each depleted sera. Our results suggest that high titers of specific Ab be obtained for both strains ofNg and the depleted sera be discriminated between both strains. These results suggest that these diagnostic reagents could be useful to confirrn presumptive identification by a simple and rapid method.

Idiopathic urethritis in young men in the United States: prevalence and comparison to infections with known sexually transmitted pathogens.

Science.gov (United States)

Wetmore, Catherine M; Manhart, Lisa E; Golden, Matthew R

2009-11-01

Urethritis is the most common male reproductive tract disease syndrome; yet 20-50% of diagnosed cases have no defined etiology, and few population-level data exist on the prevalence or etiology of the syndrome. We estimated the prevalence of urethritis among young men in the United States and compared correlates of idiopathic cases to correlates of detected infections with sexually transmitted pathogens. Questionnaire data and urine specimens from 5,447 men aged 18-27 years participating in Wave III of the National Longitudinal Study of Adolescent Health were analyzed. Symptomatic urethritis was defined as self-reported dysuria or urethral discharge in the past 24hours. Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium were identified using nucleic acid amplification tests. Idiopathic urethritis (IU) was defined as urethral symptoms in the absence of these four pathogens. Stratified weighted analyses generated population-based estimates. Urethritis was reported by 1.2% (95% CI=.8-1.6%) of men, of whom 82.4% (61.1-93.3%) had IU. Men with previous STD diagnoses (aOR=9.3 [95% CI=3.0-28.7]), or fewer (1-4) or no lifetime vaginal sex partners (aOR=7.5 [2.9-19.3] and aOR=7.2 [1.9-27.4]), were more likely to have IU compared with men without urethral symptoms or identified pathogens, whereas men of Native American or Asian/Pacific Islander descent (aOR=.04 [.01-.2]) and heavy drinkers (aOR=.08 [.03-.2]) were less likely to have IU. Unlike infection with known pathogens, IU was not associated with black race, Hispanic ethnicity, or age at sexual debut. Urethral symptoms were rarely associated with known pathogens. IU and known pathogens were associated with distinct characteristics.

Draft Genome Sequence of Neisseria gonorrhoeae Strain NG_869 with Penicillin, Tetracycline and Ciprofloxacin Resistance Determinants Isolated from Malaysia

OpenAIRE

Ang, Geik Yong; Yu, Choo Yee; Yong, Delicia Ann; Cheong, Yuet Meng; Yin, Wai-Fong; Chan, Kok-Gan

2016-01-01

Gonorrhea is a sexually transmitted infection caused by Neisseria gonorrhoeae and the increasing reports of multidrug-resistant gonococcal isolates are a global public health care concern. Herein, we report the genome sequence of N. gonorrhoeae strain NG_869 isolated from Malaysia which may provide insights into the drug resistance determinants in gonococcal bacteria.

AtlA Functions as a Peptidoglycan Lytic Transglycosylase in the Neisseria gonorrhoeae Type IV Secretion System▿

OpenAIRE

Kohler, Petra L.; Hamilton, Holly L.; Cloud-Hansen, Karen; Dillard, Joseph P.

2007-01-01

Type IV secretion systems require peptidoglycan lytic transglycosylases for efficient secretion, but the function of these enzymes is not clear. The type IV secretion system gene cluster of Neisseria gonorrhoeae encodes two peptidoglycan transglycosylase homologues. One, LtgX, is similar to peptidoglycan transglycosylases from other type IV secretion systems. The other, AtlA, is similar to endolysins from bacteriophages and is not similar to any described type IV secretion component. We chara...

Immunogenicity, Safety, and Tolerability of Bivalent rLP2086 Meningococcal Group B Vaccine Administered Concomitantly With Diphtheria, Tetanus, and Acellular Pertussis and Inactivated Poliomyelitis Vaccines to Healthy Adolescents.

Science.gov (United States)

Vesikari, Timo; Wysocki, Jacek; Beeslaar, Johannes; Eiden, Joseph; Jiang, Qin; Jansen, Kathrin U; Jones, Thomas R; Harris, Shannon L; O'Neill, Robert E; York, Laura J; Perez, John L

2016-06-01

Concomitant administration of bivalent rLP2086 (Trumenba [Pfizer, Inc] and diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) was immunologically noninferior to DTaP/IPV and saline and was safe and well tolerated. Bivalent rLP2086 elicited robust and broad bactericidal antibody responses to diverse Neisseria meningitidis serogroup B strains expressing antigens heterologous to vaccine antigens after 2 and 3 vaccinations. Bivalent rLP2086, a Neisseria meningitidis serogroup B (MnB) vaccine (Trumenba [Pfizer, Inc]) recently approved in the United States to prevent invasive MnB disease in individuals aged 10-25 years, contains recombinant subfamily A and B factor H binding proteins (fHBPs). This study evaluated the coadministration of Repevax (diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine [DTaP/IPV]) (Sanofi Pasteur MSD, Ltd) and bivalent rLP2086. Healthy adolescents aged ≥11 to B proteins different from the vaccine antigens. Participants were randomly assigned to receive bivalent rLP2086 + DTaP/IPV (n = 373) or saline + DTaP/IPV (n = 376). Immune responses to DTaP/IPV in participants who received bivalent rLP2086 + DTaP/IPV were noninferior to those in participants who received saline + DTaP/IPV.The proportions of bivalent rLP2086 + DTaP/IPV recipients with prespecified seroprotective hSBA titers to the 4 MnB test strains were 55.5%-97.3% after vaccination 2 and 81.5%-100% after vaccination 3. The administration of bivalent rLP2086 was well tolerated and resulted in few serious adverse events. Immune responses to DTaP/IPV administered with bivalent rLP2086 to adolescents were noninferior to DTaP/IPV administered alone. Bivalent rLP2086 was well tolerated and elicited substantial and broad bactericidal responses to diverse MnB strains in a high proportion of recipients after 2 vaccinations, and these responses were further enhanced after 3 vaccinations.ClinicalTrials.gov identifier NCT01323270

New recombinant vaccines for the prevention of meningococcal B disease

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Taha MK

2012-06-01

Full Text Available Muhamed-Kheir Taha, Ala-Eddine DeghmaneInstitut Pasteur, Unit of Invasive Bacterial Infections and National Reference Center for Meningococci, Paris, FranceAbstract: Meningococcal disease is a life-threatening invasive infection (mainly septicemia and meningitis that occurs as epidemic or sporadic cases. The causative agent, Neisseria meningitidis or meningococcus, is a capsulated Gram-negative bacterium. Current vaccines are prepared from the capsular polysaccharides (that also determine serogroups and are available against strains of serogroups A, C, Y, and W-135 that show variable distribution worldwide. Plain polysaccharide vaccines were first used and subsequently conjugate vaccines with enhanced immunogenicity were introduced. The capsular polysaccharide of meningococcal serogroup B is poorly immunogenic due to similarity to the human neural cells adhesion molecule. Tailor-made, strain-specific vaccines have been developed to control localized and clonal outbreaks due to meningococci of serogroup B but no “universal” vaccine is yet available. This unmet medical need was recently overcome using several subcapsular proteins to allow broad range coverage of strains and to reduce the risk of escape variants due to genetic diversity of the meningococcus. Several vaccines are under development that target major or minor surface proteins. One vaccine (Bexsero®; Novartis, under registration, is a multicomponent recombinant vaccine that showed an acceptable safety profile and covers around 80% of the currently circulating serogroup B isolates. However, its reactogenicity in infants seems to be high and the long term persistence of the immune response needs to be determined. Its activity on carriage, and therefore transmission, is under evaluation. Indirect protection is expected through restricting strain circulation and acquisition. This vaccine covers the circulating strains according to the presence of the targeted antigens in the

Novel adjuvant based on a proteoliposome-derived cochleate structure containing native lipopolysaccharide as a pathogen-associated molecular pattern.

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Pérez, Oliver; Bracho, Gustavo; Lastre, Miriam; Mora, Nestor; del Campo, Judith; Gil, Danay; Zayas, Caridad; Acevedo, Reinaldo; González, Domingo; López, José A; Taboada, Carlos; Turtle, Cameron; Solis, Rosa L

2004-12-01

Proteoliposomes (PL) from Neisseria meningitidis B have been widely used as a core antigen for antimeningococcal vaccination. PL contain major outer membrane proteins, LPS and phospholipids, and they induce a strong Th1 immune response, but they have low stability in solution. Attending to the need for new vaccine adjuvants, we developed a highly stable cochleate structure (CS) from PL using a technology that allows easy incorporation of new antigens. We explored the ability of PLCS to activate the immune system and its possible application as an adjuvant for parenteral and mucosal routes. Our results showed that PLCS were able to upregulate the expression of MHC class II and costimulatory molecules on human dendritic cells, as well as being able to stimulate the production of soluble mediators of a Th1 response, such as IL-12 and nitric oxide. High levels of anti-PL IgG were detected in serum after i.m. or mucosal (oral and nasal) administration, but also anti-PL secretory IgA was produced in saliva following nasal delivery. The immune response polarization to a Th1 pattern was confirmed by the induction of IgG2a antibodies, positive delayed type hypersensitivity reactions, and IFN-gamma production by splenocytes from immunized mice. The adjuvant potential was explored using PLCS containing ovalbumin (Ova). PLCS-Ova was able to elicit a substantial increase in anti-Ova IgG compared with Ova alone. In addition, a significant reduction in lesion size was observed in mice immunized with Leishmania major antigens in PLCS after challenge with virulent protozoa, suggesting at least partial modulation of the Th2 environment induced by this parasite. In conclusion, our results support the use of PLCS as a potent Th1 adjuvant for parenteral and mucosal vaccines.

Antimicrobial susceptibility pattern of Neisseria gonorrhoeae in western Austria.

Science.gov (United States)

Allerberger, F; Kofler, H; Brezinka, C; Guggenbichler, J P; Dierich, M P

1993-01-01

From January to October 1992 24 Neisseria gonorrhoeae isolates from clinical specimens were collected at the Federal Public Health Laboratory in Innsbruck (Austria) and screened for resistance to penicillin G, erythromycin, tetracycline, spectinomycin, ceftriaxone, cefuroxime, ciprofloxacine, and silver nitrate. Patients originated from the Austrian provinces Salzburg, Tirol, and Vorarlberg, and presented with manifest gonorrhoea. Two of 24 isolates were penicillinase-producing N. gonorrhoeae. Both strains were isolated from men who had just returned from Thailand or Kenya. The isolate from Africa was also resistant to tetracycline. Five of 24 infections were acquired abroad, sex tourism being involved in four cases. The antimicrobial resistance pattern found in gonococci in western Austria revealed that topical silver nitrate and erythromycin are equally acceptable for use in prophylaxis of neonatal ophthalmia. Penicillin is still the drug of choice in the treatment of endemic infections. If gonorrhoea has been acquired abroad, especially in Asia or Africa, ceftriaxone, spectinomycin or ciprofloxazine are recommended for therapy.

Usefulness of the DNA-fingerprinting pattern and the multilocus enzyme electrophoresis profile in the assessment of outbreaks of meningococcal disease

DEFF Research Database (Denmark)

Weis, N; Lind, I

1996-01-01

cases were identical to the outbreak strain. None of the local serogroup C carrier strains isolated during the outbreak of serogroup C disease were identical to the outbreak strain. Both DNA-fingerprinting and MEE improved the differentiation of meningococci when compared with phenotypic......The objective of the study was to assess whether genotypic characterization by means of DNA-fingerprinting pattern (DFP) and multilocus enzyme electrophoresis (MEE) profile as compared to phenotypic characterization would improve the differentiation of Neisseria meningitidis strains associated...... in each outbreak were designated the index strains. Among the remaining 55 outbreak strains 52 were either DFP-identical or DFP-indistinguishable when compared with the one relevant out of the 4 index strains. This was only the case for 17 of the 37 strains isolated from sporadic cases caused by the same...

Meningococcal biofilm formation

DEFF Research Database (Denmark)

Lappann, M.; Haagensen, Janus Anders Juul; Claus, H.

2006-01-01

We show that in a standardized in vitro flow system unencapsulated variants of genetically diverse lineages of Neisseria meningitidis formed biofilms, that could be maintained for more than 96 h. Biofilm cells were resistant to penicillin, but not to rifampin or ciprofloxacin. For some strains......, microcolony formation within biofilms was observed. Microcolony formation in strain MC58 depended on a functional copy of the pilE gene encoding the pilus subunit pilin, and was associated with twitching of cells. Nevertheless, unpiliated pilE mutants formed biofilms showing that attachment and accumulation......X alleles was identified among genetically diverse meningococcal strains. PilX alleles differed in their propensity to support autoaggregation of cells in suspension, but not in their ability to support microcolony formation within biofilms in the continuous flow system....

[Clinical evaluations of flomoxef in respiratory tract infections].

Science.gov (United States)

Mikasa, K; Sawaki, M; Ako, H; Narita, N

1987-10-01

Flomoxef (FMOX, 6315-S), a new antibacterial drug, was administered to 9 cases with respiratory tract infections for a duration of 8 approximately 16 days at a daily dose of 2 g. Diagnosis of these patients were bronchopneumonia 5 cases, chronic bronchitis 3 cases and acute bronchitis 1 case. From transtracheal aspiration several organisms were isolated; Haemophilus influenzae was isolated in 3 cases, Streptococcus pneumoniae in 3 cases, H. influenzae plus Branhamella catarrhalis in 1 case, Streptococcus dysgalactiae plus Neisseria meningitidis in 1 case and Corynebacterium pseudodiphtheriticum in 1 case. The clinical efficacy was good in all 9 cases, the efficacy rate was 100%. All the bacteria were eliminated. Side effects were not observed. From these results, it appears that FMOX is a valuable drug in the treatment of respiratory tract infections.

Meningencefalite por Pasteurella multocida: estudo clínico-laboratorial de um caso em lactente

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C. E. Levy

1989-12-01

Full Text Available Os autores apresentam descrição clínico-laboratorial e evolutiva do caso de lactente com o diagnóstico de meningencefalite por Pasteurella multocida que apresentou na evolução atraso neuromotor, manifestações epilépticas, surdez neurossensorial e paresia crural à esquerda. Fazem também breve revisão do papel deste agente etiológico na patologia humana. Ressaltam a importância da P. multocida em casos de meningites bacterianas, fazendo-se o diagnóstico laboratorial diferencial com o Haemophilus influenzae e Neisseria meningitidis em processos infecciosos conseqüentes a arranhadura ou mordida de animais e nas bacteremias ou septicemias em pacientes com hepatopatias crônicas ou em estados de imunodepressão.

Rapid differentiation of rocky mountain spotted fever from chickenpox, measles, and enterovirus infections and bacterial meningitis by frequency-pulsed electron capture gas-liquid chromatographic analysis of sera.

Science.gov (United States)

Brooks, J B; McDade, J E; Alley, C C

1981-01-01

Normal sera and sera from patients with Rocky Mountain spotted fever, chickenpox, enterovirus infections, measles, and Neisseria meningitidis infections were extracted with organic solvents under acidic and basic conditions and then derivatized with trichloroethanol or heptafluorobutyric anhydride-ethanol to form electron-capturing derivatives of organic acids, alcohols, and amines. The derivatives were analyzed by frequency-pulsed electron capture gas-liquid chromatography (FPEC-GLC). There were unique differences in the FPEC-GLC profiles of sera obtained from patients with these respective diseases. With Rocky Mountain spotted fever patients, typical profiles were detected as early as 1 day after onset of disease and before antibody could be detected in the serum. Rapid diagnosis of Rocky Mountain spotted fever by FPEC-GLC could permit early and effective therapy, thus preventing many deaths from this disease. PMID:7276147

In Vitro Susceptibility of Neisseria gonorrhoeae Strains to Mupirocin, an Antibiotic Reformulated for Parenteral Administration in Nanoliposomes.

Science.gov (United States)

Cern, Ahuva; Connolly, Kristie L; Jerse, Ann E; Barenholz, Yechezkel

2018-04-01

Neisseria gonorrhoeae is an urgent antibiotic-resistant threat. This study determined the MICs of mupirocin to be 0.0039 to 0.0625 μg/ml for 94 N. gonorrhoeae strains. Cross-resistance with other antibiotics was not detected. Mupirocin, which is currently limited to topical administration, demonstrated activity by injection when delivered in nanoliposomes. The nanoliposomal formulation of mupirocin is a potential treatment for drug-resistant N. gonorrhoeae . Copyright © 2018 American Society for Microbiology.

Evaluación de la eficacia de VA-MENGOC-BC® en ratón Balb/c retados frente a los serogrupos A, B y C

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Juan Francisco Infante

2003-09-01

Full Text Available Hasta la fecha se han desarrollado varios modelos experimentales para la reproducción experimental de la enfermedad meningocócica humana, cuya utilidad en la evaluación de la eficacia de medios de inmunización y terapia, así como en el estudio de la patogenia de la enfermedad es incuestionable. En el presente trabajo se describe la evaluación de la eficacia de VA-MENGOC-BC® y la Inmunoglobulina Humana Antimeningocócica BC frente a Neisseria meningitidis de los serogrupos A, B y C, empleando el ratón Balb/c tratado con mucina y dextrana férrica como estimulantes de la virulencia. Los ratones fueron inmunizados por vía intraperitoneal con una, dos o tres dosis de 0,5 mL de VA-MENGOC-BC®. El intervalo entre dosis fue de tres semanas entre la primera y segunda dosis y de 15 días entre la segunda y la tercera. El reto se realizó con dosis letales (1-3 x DL50 de N. meningitidis A, B ó C a los 15 ó 21 días después de aplicada la última dosis de vacuna. Para evaluar la actividad de la Inmunoglobulina Antimeningocócica BC como medio de inmunización pasiva, se trató otro grupo de ratones, 30 min, 2 y 6 h después habérseles inoculado los gérmenes. Se administraron en cada caso 5 mg de la inmunoglobulina por vía intraperitoneal o intravenosa en un volumen de 0,1 mL. Los resultados demostraron que tanto VA-MENGOC-BC® como la Globulina Antimeningocócica BC confieren protección significativa contra un reto letal con N. meningitidis en el modelo de ratón tratado con factores estimulantes de la virulencia.

A Novel Mechanism of High-Level, Broad-Spectrum Antibiotic Resistance Caused by a Single Base Pair Change in Neisseria gonorrhoeae

Science.gov (United States)

2011-09-20

respect, Eisenstein and Sparling noted that a single base pair deletion in the inverted repeat in the mtrR promoter, a mutation which also confers high...Regulation of the MtrC-MtrD-MtrE efflux-pump system modulates the in vivo fitness of Neisseria gonorrhoeae. J. Infect. Dis. 196:1804 –1812. 21. Eisenstein BI

Global epidemiology of serogroup B meningococcal disease and opportunities for prevention with novel recombinant protein vaccines.

Science.gov (United States)

Villena, Rodolfo; Safadi, Marco Aurelio P; Valenzuela, María Teresa; Torres, Juan P; Finn, Adam; O'Ryan, Miguel

2018-04-18

Meningococcal disease (MD) is a major cause of meningitis and sepsis worldwide, with a high case fatality rate and frequent sequelae. Neisseria meningitidis serogroups A, B, C, W, X and Y are responsible for most of these life-threatening infections, and its unpredictable epidemiology can cause outbreaks in communities, with significant health, social and economic impact. Currently, serogroup B is the main cause of MD in Europe and North America and one of the most prevalent serogroups in Latin America. Mass vaccination strategies using polysaccharide vaccines have been deployed since the 1970s and the use of conjugate vaccines has controlled endemic and epidemic disease caused by serogroups A, C, W and Y and more recently serogroup B using geographically-specific outer membrane vesicle based vaccines. Two novel protein-based vaccines are a significant addition to our armamentarium against N. meningitidis as they provide broad coverage against highly diverse strains in serogroup B and other groups. Early safety, effectiveness and impact data of these vaccines are encouraging. These novel serogroup B vaccines should be actively considered for individuals at increased risk of disease and to control serogroup B outbreaks occurring in institutions or specific regions, as they are likely to save lives and prevent severe sequelae. Incorporation into national programs will require thorough country-specific analysis.

The influence of IS1301 in the capsule biosynthesis locus on meningococcal carriage and disease.

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Elisabeth Kugelberg

2010-02-01

Full Text Available Previously we have shown that insertion of IS1301 in the sia/ctr intergenic region (IGR of serogroup C Neisseria meningitidis (MenC isolates from Spain confers increased resistance against complement-mediated killing. Here we investigate the significance of IS1301 in the same location in N. meningitidis isolates from the UK. PCR and sequencing was used to screen a collection of more than 1500 meningococcal carriage and disease isolates from the UK for the presence of IS1301 in the IGR. IS1301 was not identified in the IGR among vaccine failure strains but was frequently found in serogroup B isolates (MenB from clonal complex 269 (cc269. Almost all IS1301 insertions in cc269 were associated with novel polymorphisms, and did not change capsule expression or resistance to human complement. After excluding sequence types (STs distant from the central genotype within cc269, there was no significant difference for the presence of IS1301 in the IGR of carriage isolates compared to disease isolates. Isolates with insertion of IS1301 in the IGR are not responsible for MenC disease in UK vaccine failures. Novel polymorphisms associated with IS1301 in the IGR of UK MenB isolates do not lead to the resistance phenotype seen for IS1301 in the IGR of MenC isolates.

Characterisation of the Immunomodulatory Effects of Meningococcal Opa Proteins on Human Peripheral Blood Mononuclear Cells and CD4+ T Cells.

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Claire Jones

Full Text Available Opa proteins are major surface-expressed proteins located in the Neisseria meningitidis outer membrane, and are potential meningococcal vaccine candidates. Although Opa proteins elicit high levels of bactericidal antibodies following immunisation in mice, progress towards human clinical trials has been delayed due to previous findings that Opa inhibits T cell proliferation in some in vitro assays. However, results from previous studies are conflicting, with different Opa preparations and culture conditions being used. We investigated the effects of various Opa+ and Opa- antigens from N. meningitidis strain H44/76 in a range of in vitro conditions using peripheral blood mononuclear cells (PBMCs and purified CD4+ T cells, measuring T cell proliferation by CFSE dilution using flow cytometry. Wild type recombinant and liposomal Opa proteins inhibited CD4+ T cell proliferation after stimulation with IL-2, anti-CD3 and anti-CD28, and these effects were reduced by mutation of the CEACAM1-binding region of Opa. These effects were not observed in culture with ex vivo PBMCs. Opa+ and Opa- OMVs did not consistently exert a stimulatory or inhibitory effect across different culture conditions. These data do not support a hypothesis that Opa proteins would be inhibitory to T cells if given as a vaccine component, and T cell immune responses to OMV vaccines are unlikely to be significantly affected by the presence of Opa proteins.

Cross-protection in Neisseria meningitidis serogroups Y and W polysaccharides: A comparative conformational analysis.

Science.gov (United States)

Kuttel, Michelle M; Timol, Zaheer; Ravenscroft, Neil

2017-06-29

The capsular polysaccharide is the main virulence factor in meningococcus. The capsular polysaccharides for meningococcal serogroups Y and W are almost identical polymers of hexose-sialic acid, suggesting the possibility of cross-protection between group Y and W vaccines. However, early studies indicated that they elicit different levels of cross-protection. Here we explore the conformations of the meningococcal Y and W polysaccharides with molecular dynamics simulations of three repeating unit oligosaccharide strands. We find differences in Y and W antigen conformation: the Y polysaccharide has a single dominant conformation, whereas W exhibits a family of conformations including the Y conformation. This result is supported by our NMR NOESY analysis, which indicates key close contacts for W that are not present in Y. These conformational differences provide an explanation for the different levels of cross-protection measured for the Y and W monovalent vaccines and the high group W responses observed in HibMenCY-TT vaccinees. Copyright © 2017 Elsevier Ltd. All rights reserved.

CRISPR/Cas systems: new players in gene regulation and bacterial physiology

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David eWeiss

2014-04-01

Full Text Available CRISPR-Cas systems are bacterial defenses against foreign nucleic acids derived from bacteriophages, plasmids or other sources. These systems are targeted in an RNA-dependent, sequence-specific manner, and are also adaptive, providing protection against previously encountered foreign elements. In addition to their canonical function in defense against foreign nucleic acid, their roles in various aspects of bacterial physiology are now being uncovered. We recently revealed a role for a Cas9-based Type II CRISPR-Cas system in the control of endogenous gene expression, a novel form of prokaryotic gene regulation. Cas9 functions in association with two small RNAs to target and alter the stability of an endogenous transcript encoding a bacterial lipoprotein (BLP. Since BLPs are recognized by the host innate immune protein Toll-like Receptor 2 (TLR2, CRISPR-Cas-mediated repression of BLP expression facilitates evasion of TLR2 by the intracellular bacterial pathogen Francisella novicida, and is essential for its virulence. Here we describe the Cas9 regulatory system in detail, as well as data on its role in controlling virulence traits of Neisseria meningitidis and Campylobacter jejuni. We also discuss potential roles of CRISPR-Cas systems in the response to envelope stress and other aspects of bacterial physiology. Since ~45% of bacteria and ~83% of Archaea encode these machineries, the newly appreciated regulatory functions of CRISPR-Cas systems are likely to play broad roles in controlling the pathogenesis and physiology of diverse prokaryotes.

Lactoferrin binding protein B - a bi-functional bacterial receptor protein.

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Nicholas K H Ostan

2017-03-01

Full Text Available Lactoferrin binding protein B (LbpB is a bi-lobed outer membrane-bound lipoprotein that comprises part of the lactoferrin (Lf receptor complex in Neisseria meningitidis and other Gram-negative pathogens. Recent studies have demonstrated that LbpB plays a role in protecting the bacteria from cationic antimicrobial peptides due to large regions rich in anionic residues in the C-terminal lobe. Relative to its homolog, transferrin-binding protein B (TbpB, there currently is little evidence for its role in iron acquisition and relatively little structural and biophysical information on its interaction with Lf. In this study, a combination of crosslinking and deuterium exchange coupled to mass spectrometry, information-driven computational docking, bio-layer interferometry, and site-directed mutagenesis was used to probe LbpB:hLf complexes. The formation of a 1:1 complex of iron-loaded Lf and LbpB involves an interaction between the Lf C-lobe and LbpB N-lobe, comparable to TbpB, consistent with a potential role in iron acquisition. The Lf N-lobe is also capable of binding to negatively charged regions of the LbpB C-lobe and possibly other sites such that a variety of higher order complexes are formed. Our results are consistent with LbpB serving dual roles focused primarily on iron acquisition when exposed to limited levels of iron-loaded Lf on the mucosal surface and effectively binding apo Lf when exposed to high levels at sites of inflammation.

[A case of bacterial peritonitis caused by Neisseria gonorrhoeae].

Science.gov (United States)

Akahane, T; Kawakami, Y; Oana, K

2001-10-01

On January 17, 2001, a 39-year old female with sudden abdominal pain was admitted to her neighboring outpatient clinic and diagnosed as suspicious of infectious enteritis. However, on the next day (January 18, 2001) she was soon transferred to Toyoshina Red Cross Hospital with the chief complaint of severe abdominal pain, high fever, and of conspicuous leucocytosis. Laboratory data on her admission demonstrated apparent signs of inflammation and she was soon undergone an emergency operation. Neisseria gonorrhoeae was recovered from her ascetic fluid, otherwise Chlamydia EIA was negative. The antibiotic chemotherapy of minocycline (200 mg/day) was continued for the first 9 days and sulbactam/cefoperazone (2 g/day) had been administered for the first 5 days. Her symptoms were discontinued on her 10th hospital day, and she was discharged on the 14th hospital day. There have been few reported cases in Japan of bacterial peritonitis due to N. gonorrhoeae. This is, to the best of our knowledge, the first reported case of N. gonorrhoeae peritonitis in Japan.

NERVE: New Enhanced Reverse Vaccinology Environment

Directory of Open Access Journals (Sweden)

Filippini Francesco

2006-07-01

Full Text Available Abstract Background Since a milestone work on Neisseria meningitidis B, Reverse Vaccinology has strongly enhanced the identification of vaccine candidates by replacing several experimental tasks using in silico prediction steps. These steps have allowed scientists to face the selection of antigens from the predicted proteome of pathogens, for which cell culture is difficult or impossible, saving time and money. However, this good example of bioinformatics-driven immunology can be further developed by improving in silico steps and implementing biologist-friendly tools. Results We introduce NERVE (New Enhanced Reverse Vaccinology Environment, an user-friendly software environment for the in silico identification of the best vaccine candidates from whole proteomes of bacterial pathogens. The software integrates multiple robust and well-known algorithms for protein analysis and comparison. Vaccine candidates are ranked and presented in a html table showing relevant information and links to corresponding primary data. Information concerning all proteins of the analyzed proteome is not deleted along selection steps but rather flows into an SQL database for further mining and analyses. Conclusion After learning from recent years' works in this field and analysing a large dataset, NERVE has been implemented and tuned as the first available tool able to rank a restricted pool (~8–9% of the whole proteome of vaccine candidates and to show high recall (~75–80% of known protective antigens. These vaccine candidates are required to be "safe" (taking into account autoimmunity risk and "easy" for further experimental, high-throughput screening (avoiding possibly not soluble antigens. NERVE is expected to help save time and money in vaccine design and is available as an additional file with this manuscript; updated versions will be available at http://www.bio.unipd.it/molbinfo.

Consensus recommendation for meningococcal disease prevention for Hajj and Umra pilgrimage/travel medicine.

Science.gov (United States)

Shibl, A; Tufenkeji, H; Khalil, M; Memish, Z

2013-04-01

The Islamic Hajj to Makkah (Mecca) has been associated with outbreaks of invasive meningococcal disease and the global spread of Neisseria meningitidis serogroup W-135. For Hajj pilgrims the quadrivalent vaccination against serogroups A, C, W-135 and Y is a mandatory requirement. Novel conjugate vaccines may provide benefits for the community by reduction of carriage. With the introduction of the new generation of quadrivalent meningococcal conjugate vaccines (Menveo, Menactra, and others pending license) and their recent implementation in Saudi Arabia, experts from 11 countries in the Middle East region met at a Meningococcal Leadership Forum (MLF), in Dubai in May 2010 to exchange opinions on meningococcal disease and prevention strategies. These experts discussed the importance of introducing conjugate vaccines for pilgrims and travellers, and elaborated a consensus recommendation to support healthcare professionals and decision-makers.

Global invasive bacterial vaccine-preventable diseases surveillance--2008-2014.

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Murray, Jillian; Agócs, Mary; Serhan, Fatima; Singh, Simarjit; Deloria-Knoll, Maria; O'Brien, Katherine; Mwenda, Jason M; Mihigo, Richard; Oliveira, Lucia; Teleb, Nadia; Ahmed, Hinda; Wasley, Annemarie; Videbaek, Dovile; Wijesinghe, Pushpa; Thapa, Arun Bhadra; Fox, Kimberly; Paladin, Fem Julia; Hajjeh, Rana; Schwartz, Stephanie; Van Beneden, Chris; Hyde, Terri; Broome, Claire; Cherian, Thomas

2014-12-12

Meningitis and pneumonia are leading causes of morbidity and mortality in children globally infected with Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis, and Haemophilus influenzae causing a large proportion of disease. Vaccines are available to prevent many of the common types of these infections. S. pneumoniae was estimated to have caused 11% of deaths in children aged Organization (WHO) has recommended inclusion of PCV in childhood immunization programs worldwide, especially in countries with high child mortality. As of November 26, 2014, a total of 112 (58%) of all 194 WHO member states and 44 (58%) of the 76 member states ever eligible for support from Gavi, the Vaccine Alliance (Gavi), have introduced PCV. Invasive pneumococcal disease (IPD) surveillance that includes data on serotypes, along with meningitis and pneumonia syndromic surveillance, provides important data to guide decisions to introduce PCV and monitor its impact.

Gonorrhea in Indonesia: High Prevalence of Asymptomatic Urogenital Gonorrhea but No Circulating Extended Spectrum Cephalosporins-Resistant Neisseria gonorrhoeae Strains in Jakarta, Yogyakarta, and Denpasar, Indonesia

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Hananta, I. Putu Yuda; van Dam, Alje P.; Bruisten, Sylvia Maria; Schim van der Loeff, Maarten Franciscus; Soebono, Hardyanto; de Vries, Henry John Christiaan

2016-01-01

Little is known about the epidemiology of asymptomatic urogenital gonorrhea and antimicrobial susceptibility of Neisseria gonorrhoeae (NG) strains circulating in Indonesia. We studied these issues in 3 large Indonesian cities. In 2014, participants were recruited from sexually transmitted infection

Carriage of Streptococcus pneumoniae and other respiratory bacterial pathogens in low and lower-middle income countries: a systematic review and meta-analysis.

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Richard A Adegbola

Full Text Available Infection with Streptococcus pneumoniae is a major cause of childhood morbidity and mortality worldwide, especially in low income countries where pneumococcal conjugate vaccines (PCVs are still underused. In countries where PCVs have been introduced, much of their efficacy has resulted from their impact on nasopharyngeal carriage in vaccinated children. Understanding the epidemiology of carriage for S. pneumoniae and other common respiratory bacteria in developing countries is crucial for implementing appropriate vaccination strategies and evaluating their impact.We have systematically reviewed published studies reporting nasopharyngeal or oropharyngeal carriage of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Neisseria meningitidis in children and adults in low and lower-middle income countries. Studies reporting pneumococcal carriage for healthy children <5 years of age were selected for a meta-analysis. The prevalences of carriage for S. pneumoniae, H. influenzae, and M. catarrhalis were generally higher in low income than in lower-middle income countries and were higher in young children than in adults. The prevalence of S. aureus was high in neonates. Meta-analysis of data from young children before the introduction of PCVs showed a pooled prevalence estimate of 64.8% (95% confidence interval, 49.8%-76.1% in low income countries and 47.8% (95% confidence interval, 44.7%-50.8% in lower-middle income countries. The most frequent serotypes were 6A, 6B, 19A, 19F, and 23F.In low and lower-middle income countries, pneumococcal carriage is frequent, especially in children, and the spectrum of serotypes is wide. However, because data are limited, additional studies are needed to adequately assess the impact of PCV introduction on carriage of respiratory bacteria in these countries.

Identification of Novel Immunogenic Proteins of Neisseria gonorrhoeae by Phage Display.

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Daniel O Connor

Full Text Available Neisseria gonorrhoeae is one of the most prevalent sexually transmitted diseases worldwide with more than 100 million new infections per year. A lack of intense research over the last decades and increasing resistances to the recommended antibiotics call for a better understanding of gonococcal infection, fast diagnostics and therapeutic measures against N. gonorrhoeae. Therefore, the aim of this work was to identify novel immunogenic proteins as a first step to advance those unresolved problems. For the identification of immunogenic proteins, pHORF oligopeptide phage display libraries of the entire N. gonorrhoeae genome were constructed. Several immunogenic oligopeptides were identified using polyclonal rabbit antibodies against N. gonorrhoeae. Corresponding full-length proteins of the identified oligopeptides were expressed and their immunogenic character was verified by ELISA. The immunogenic character of six proteins was identified for the first time. Additional 13 proteins were verified as immunogenic proteins in N. gonorrhoeae.

Prevalence of Chlamydia trachomatis, Trichomonas vaginalis and Neisseria gonorrhoeae Based on Data Collected by a Network of Clinical Microbiology Laboratories, in Italy.

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Salfa, Maria Cristina; Suligoi, Barbara

Bacterial and protozoal sexually transmitted infections (STIs), such as Chlamydia trachomatis, Trichomonas vaginalis and Neisseria gonorrhoeae, may cause acute symptoms, chronic infections and severe long-term complications. The complications of these infections in women include pelvic inflammatory disease, chronic pelvic pain, tubal infertility, ectopic pregnancy, and infertility. Moreover, infection during pregnancy is associated with premature rupture of the membranes, low birth weight and miscarriage.In Italy, Chlamydia trachomatis and Trichomonas vaginalis infections are not subject to mandatory reporting; while gonorrhoea is subject to mandatory reporting.To extend surveillance to STIs that are widespread yet often asymptomatic and to improve the knowledge on the epidemiology of these infections in Italy, in 2009 the "Centro Operativo AIDS of the Istituto Superiore di SanitÁ", in collaboration with the Association of Italian Clinical Microbiologists (AMCLI, Associazione Microbiologi Clinici Italiani), launched the sentinel STIs surveillance system based on a network of 13 clinical microbiology laboratories.The main objective of the surveillance was to assess the prevalence and risk factors associated with Chlamydia trachomatis, Trichomonas vaginalis and Neisseria gonorrhoea infections among individuals attending microbiology laboratories in Italy.

Neisseria gonorrhoeae co-infection exacerbates vaginal HIV shedding without affecting systemic viral loads in human CD34+ engrafted mice.

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Stacey X Xu

Full Text Available HIV synergy with sexually transmitted co-infections is well-documented in the clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital HIV shedding and mucosal transmission. However, no animal model of co-infection currently exists to directly explore this relationship or to bridge the gap in understanding between clinical and in vitro studies of this interaction. This study aims to test the feasibility of using a humanized mouse model to overcome this barrier. Combining recent in vivo modelling advancements in both HIV and gonococcal research, we developed a co-infection model by engrafting immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae infection. Systemic plasma and vaginal lavage titres of HIV were measured in order to assess the impact of gonococcal challenge on viral plasma titres and genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels but higher viral shedding in the genital tract, which reflects published clinical observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an experimentally tractable animal model in which to study HIV shedding during gonococcal co-infection, allowing dissection of molecular and immunological interactions between these pathogens, and providing a platform to assess future therapeutics aimed at reducing HIV transmission.

Neisseria gonorrhoeae co-infection exacerbates vaginal HIV shedding without affecting systemic viral loads in human CD34+ engrafted mice.

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Xu, Stacey X; Leontyev, Danila; Kaul, Rupert; Gray-Owen, Scott D

2018-01-01

HIV synergy with sexually transmitted co-infections is well-documented in the clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital HIV shedding and mucosal transmission. However, no animal model of co-infection currently exists to directly explore this relationship or to bridge the gap in understanding between clinical and in vitro studies of this interaction. This study aims to test the feasibility of using a humanized mouse model to overcome this barrier. Combining recent in vivo modelling advancements in both HIV and gonococcal research, we developed a co-infection model by engrafting immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae infection. Systemic plasma and vaginal lavage titres of HIV were measured in order to assess the impact of gonococcal challenge on viral plasma titres and genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels but higher viral shedding in the genital tract, which reflects published clinical observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an experimentally tractable animal model in which to study HIV shedding during gonococcal co-infection, allowing dissection of molecular and immunological interactions between these pathogens, and providing a platform to assess future therapeutics aimed at reducing HIV transmission.

Agar dilution method for susceptibility testing of Neisseria gonorrhoeae

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Marta C de Castillo

1996-12-01

Full Text Available The antibiotic susceptibilities of Neisseria gonorrhoeae isolates obtained from patients attending a clinic for sexually transmitted diseases in Tucumán, Argentina, were determined by the agar dilution method (MIC. 3.5% of the isolates produced ²-lactamase. A total of 96.5% of ²-lactamase negative isolates tested were susceptible to penicillin (MIC < 2 µgml-1; 14.03% of the tested isolates were resistant to tetracycline (MIC < 2 µgml-1, and 98% of the tested isolates were susceptible to spectinomycin (MIC < 64 µgml-1. The MICs for 95% of the isolates, tested for other drugs were: < 2 µgml-1 for cefoxitin, < 0.06 µgml-1 for cefotaxime, < 0.25 µgml-1 for norfloxacin, < 10 µgml-1 for cephaloridine, < 10 µgml-1 for cephalexin, and < 50 µgml-1 for kanamycin. Antibiotic resistance among N. gonorrhoeae isolates from Tucumán, Argentina, appeared to be primarily limited to penicillin and tetracycline, which has been a general use against gonorrhoeae in Tucumán since 1960. Periodic monitoring of the underlying susceptibility profiles of the N. gonorrhoeae strains prevalent in areas of frequent transmission may provide clues regarding treatment options and emerging of drug resistance.

Characterization of a catalase-deficient strain of Neisseria gonorrhoeae: evidence for the significance of catalase in the biology of N. gonorrhoeae.

OpenAIRE

Johnson, S R; Steiner, B M; Cruce, D D; Perkins, G H; Arko, R J

1993-01-01

We obtained a catalase-deficient (Kat-) strain of Neisseria gonorrhoeae isolated from a patient who had been unsuccessfully treated with penicillin. Quantitative enzyme assays and electrophoresis of cell extracts on native polyacrylamide gels subsequently stained for catalase and peroxidase activities failed to detect both enzymes. The strain exhibited no growth anomalies or unusual requirements when grown under ordinary laboratory conditions. However, the Kat- strain proved extremely sensiti...

Las meningoencefalitis bacterianas en la población infantil cubana: 1998-2000

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Félix Orlando Dickinson Meneses

2002-06-01

Full Text Available Se describen algunos aspectos epidemiológicos de las meningoencefalitis bacterianas (MEB en Cuba entre 1998 y el año 2000, según los datos de la Vigilancia Nacional de las MEB (VNMEB disponibles. Se reportaron un total de 530 casos en menores de 15 años en todo el país durante el período. El grupo de edad más afectado resultó el de menos de 5 años. Los agentes más frecuentemente identificados fueron Haemophilus influenzae tipo b (Hib, Streptococcus pneumoniae (Spn y Neisseria meningitidis (Nm. La incidencia de Hib disminuyó 4 veces por el efecto de la vacunación masiva, especialmente en los menores de 5 años, a partir del año 2000 Spn es el principal agente causante de MEB y el más letal en Cuba. La letalidad general se incrementó de 10,6 a 20,4 %, y fue el grupo de los de menos de 1 año uno de los más afectados. Futuros estudios permitirán profundizar en la epidemiología de estas infecciones y monitorear los cambios que ocurran como consecuencia de intervenciones.Somme epidemiological aspects of bacterial meningoencephalities that occurred in Cuba from 1998-2000 are described according to available data from the National Surveillance Service. A total of 530 cases involving children under 15 years old were reported throughout the country in this period of time. The most affected age group was under 5 years. The most frequent identified agents were Haemophilus influenzae type B(Hib, Streptococcus pneumoniae (Spn and Neisseria meningitidis (Nm. The incidence of Hib decreased by 4 times thanks to massive vaccination program, particularly in under 5 years-old children, from the year 2000 on. Spn is the main causative agent of bacterial meningoencephalities and the most lethal one in Cuba. General lethality rate increased from 10.6 to 20.4% and the under one-year old age group was the most affected. Further studies will allow deepening into the epidemiology of these infections and monitoring the changes that might occur as a

Ribosomal proteins as biomarkers for bacterial identification by mass spectrometry in the clinical microbiology laboratory.

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Suarez, Stéphanie; Ferroni, Agnès; Lotz, Aurélie; Jolley, Keith A; Guérin, Philippe; Leto, Julie; Dauphin, Brunhilde; Jamet, Anne; Maiden, Martin C J; Nassif, Xavier; Armengaud, Jean

2013-09-01

Whole-cell matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a rapid method for identification of microorganisms that is increasingly used in microbiology laboratories. This identification is based on the comparison of the tested isolate mass spectrum with reference databases. Using Neisseria meningitidis as a model organism, we showed that in one of the available databases, the Andromas database, 10 of the 13 species-specific biomarkers correspond to ribosomal proteins. Remarkably, one biomarker, ribosomal protein L32, was subject to inter-strain variability. The analysis of the ribosomal protein patterns of 100 isolates for which whole genome sequences were available, confirmed the presence of inter-strain variability in the molecular weight of 29 ribosomal proteins, thus establishing a correlation between the sequence type (ST) and/or clonal complex (CC) of each strain and its ribosomal protein pattern. Since the molecular weight of three of the variable ribosomal proteins (L30, L31 and L32) was included in the spectral window observed by MALDI-TOF MS in clinical microbiology, i.e., 3640-12000 m/z, we were able by analyzing the molecular weight of these three ribosomal proteins to classify each strain in one of six subgroups, each of these subgroups corresponding to specific STs and/or CCs. Their detection by MALDI-TOF allows therefore a quick typing of N. meningitidis isolates. © 2013 Elsevier B.V. All rights reserved.

Risk factors for antimicrobial-resistant Neisseria gonorrhoeae and characteristics of patients infected with gonorrhea.

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Fuertes de Vega, Irene; Baliu-Piqué, Carola; Bosch Mestres, Jordi; Vergara Gómez, Andrea; Vallés, Xavier; Alsina Gibert, Mercè

2018-03-01

There are very few data available regarding risk factors associated with antibiotic resistant-Neisseria gonorrhoeae. A study was conducted on 110 samples from 101 patients with gonococcal infection, in order to describe their characteristics and compare them with the antimicrobial susceptibility profile of their samples. An association was observed between resistant infections and heterosexual men, older age, concurrent sexually transmitted infection, and unsafe sexual behaviors. There is a need for improved data on the risk factors associated with antibiotic resistant gonococcal infection in order to identify risk groups, and to propose public health strategies to control this infection. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Detection of HPV and co-infecting pathogens in healthy Italian women by multiplex real-time PCR.

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Camporiondo, Maria Pia; Farchi, Francesca; Ciccozzi, Massimo; Denaro, Aurelia; Gallone, Domenica; Maracchioni, Fabio; Favalli, Cartesio; Ciotti, Marco

2016-01-01

Several pathogens can be transmitted sexually and are an important cause of morbidity among sexually active women. The aim of the study was to detect the presence of human papillomavirus (HPV), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Ureaplasma urealyticum (UU), and Ureaplasma parvum (UP) in a group of 309 healthy women enrolled at the San Camillo - Forlanini hospital of Rome by using two multiplex real-time PCR assays based on TOCE® technology. The women's ages ranged from 34 to 60 years, median 49 [IQR 45-54]. Of the 309 women tested, HPV DNA was detected in 77/309 (24.9%) patients. Of these, 44 (14.2%) harboured a single infection while 33 (10.7%) were infected by multiple genotypes. Prevalence of HPV infection was highest among females aged 40-50 years (15.2%). Of the other pathogens sought, CT, MG and NG were not detected while positive results were found for MH (12/309, 3.9%), TV (4/309, 1.3%), UP (89/309, 28.8%) and UU (14/309, 4.5%). Co-infections were as follows: 5 MH/HPV, 4 TV/HPV, 34 UP/HPV and 9 UU/HPV. In HPV-positive women, the probability of being infected by UP and UU was 2.5 (p=0.00045) and 6 fold higher (p=0.0016) than in HPV-negative women. The study supports the use of multiplex real-time PCR assays in a routine diagnostic setting. The high sensitivity and specificity of these assays along with the simultaneous detection of the most common sexually transmitted pathogens confers an advantage with respect to more obsolete methods reducing costs and time to diagnosis.

Strategy for determination of an efficient Cochleate particle size.

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Gil, Danay; Bracho, Gustavo; Zayas, Caridad; del Campo, Judith; Acevedo, Reinaldo; Toledo, Arturo; Lastre, Miriam; Pérez, Oliver

2006-04-12

Cochleate structures obtained from the outer membrane of Neisseria meningitidis serotype B have demonstrated to be high immunogenicity when administrated by intramuscular, oral or intranasal routes, and could be used as adjuvant and meningococcal nasal vaccine candidate. Due to the microparticulate nature of Cochleate it is necessary to control the particle size since it capture by cells of the immune system could be affected by this aspect. We combined optic microscopy and immunisation experiments to select the optimum particle size. Six different processes of producing Cochleate obtaining were evaluated and different mechanical stress conditions were carried out to homogenize and modulate the particles size. The more immunogenic particles were selected on the basis of the levels of specific IgA and IgG antibodies induced after intranasal immunisation in mice. The best treatment parameter for mechanical stress of the Cochleate was prolonged treatment with untrasonic low frequency waves.

Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions

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George P. Dinos

2016-06-01

Full Text Available Chloramphenicol (CAM is the D-threo isomer of a small molecule, consisting of a p-nitrobenzene ring connected to a dichloroacetyl tail through a 2-amino-1,3-propanediol moiety. CAM displays a broad-spectrum bacteriostatic activity by specifically inhibiting the bacterial protein synthesis. In certain but important cases, it also exhibits bactericidal activity, namely against the three most common causes of meningitis, Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. Resistance to CAM has been frequently reported and ascribed to a variety of mechanisms. However, the most important concerns that limit its clinical utility relate to side effects such as neurotoxicity and hematologic disorders. In this review, we present previous and current efforts to synthesize CAM derivatives with improved pharmacological properties. In addition, we highlight potentially broader roles of these derivatives in investigating the plasticity of the ribosomal catalytic center, the main target of CAM.

Rapid Methods for the Laboratory Identification of Pathogenic Microorganisms.

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1982-09-01

coli Hemophilus influenzae Bacillus anthracis Bacillus circulans Bacillus coagulans Bacillus cereus T Candida albicans Cryptococcus neoformans Legionel...reveree aide If neceeeary and Identify by block number) Lectins: Rapid Identification, Bacillus anthracisjCryptococcus " neoformans. Neisseria...field-type kit for the rapid identification of Bacillus anthracis. We have shown that certain lectins will selectively interact with B. anthracis

Antimicrobial blue light inactivation of Neisseria gonorrhoeae

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Wang, Ying; Gu, Ying; Dai, Tianhong

2018-02-01

Neisseria gonorrhoeae is a human-adapted, gram-negative diplococcus that infects human reproductive tracts and causes gonorrhea, a sexually transmitted disease, resulting in discharge and inflammation at the urethra, cervix, pharynx, or rectum. Over the years, N. gonorrhoeae has developed resistance to nearly every drug ever used to treat it, including sulfonamides, penicillin, tetracycline, and fluoroquinolones. Drug-resistant N. gonorrhoeae is now considered by the Centers for Disease Control and Prevention (CDC) as an urgent threat. The present study aimed to evaluate the efficacy of antimicrobial blue light (aBL) at 405 and 470 nm for inactivating N. gonorrhoeae and reveal the mechanism of action. Our results showed that an exposure of 45 J/cm2 aBL at 405 nm reduced the bacterial CFU by 7.16-log10. When the aBL exposure was increased to 54 J/cm2, eradication of bacterial CFU was achieved. When the bacteria were exposed to aBL at 470 nm, 3-log10 reduction of CFU was observed at an aBL exposure of higher than 126 J/cm2. Absorption and fluorescence spectroscopic analyses revealed the presence of endogenous porphyrins and flavins in N. gonorrhoeae cells. The present study indicated that aBL is a potential strategy to control N. gonorrhoeae infections. Endogenous porphyrins play a vital role in the killing effects of aBL. In vivo experiments are ongoing in our laboratory to treat genital tract infections in mice using aBL and explore the potential clinical applications.

Understanding Bacterial Isolates in Blood Culture and Approaches Used to Define Bacteria as Contaminants: A Literature Review.

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Hossain, Belal; Islam, Mohammad Shahidul; Rahman, Atiqur; Marzan, Mahfuza; Rafiqullah, Iftekhar; Connor, Nicholas E; Hasanuzzaman, Mohammad; Islam, Maksuda; Hamer, Davidson H; Hibberd, Patricia L; Saha, Samir K

2016-05-01

Interpretation of blood culture isolates is challenging due to a lack of standard methodologies for identifying contaminants. This problem becomes more complex when the specimens are from sick young infants, as a wide range of bacteria can cause illness among this group. We used 43 key words to find articles published between 1970 and 2011 on blood culture isolates and possible contaminants in the PubMed database. Experts were also consulted to obtain other relevant articles. Selection of articles followed systematic methods considering opinions from more than 1 reviewer. After reviewing the titles of 3869 articles extracted from the database, we found 307 relevant to our objective. Based on the abstracts, 42 articles were selected for the literature review. In addition, we included 7 more articles based on cross-references and expert advice. The most common methods for differentiating blood culture isolates were multiple blood cultures from the same subject, antibiograms and molecular testing. Streptococcus pneumoniae, Hemophilus influenzae, Neisseria meningitidis and group A and B streptococcus were always considered as pathogens, whereas Bacillus sp., Diphtheroids, Propionibacterium and Micrococcus were commonly regarded as contaminants. Coagulase-negative staphylococci were the most frequent isolates and usually reported as contaminants unless the patient had a specific condition, such as long-term hospitalization or use of invasive devices (catheters). Inaccurate interpretation of blood culture may falsely guide treatment and also has long-term policy implications. The combination of clinical and microbiological knowledge, patient's clinical history and laboratory findings are essential for appropriate interpretation of blood culture.

Influence of medium components on the expression of recombinant lipoproteins in Escherichia coli.

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Tseng, Chi-Ling; Leng, Chih-Hsiang

2012-02-01

Bacterial lipoproteins are crucial antigens for protective immunity against bacterial pathogens. Expression of exogenous lipoproteins in Escherichia coli at high levels is thought to be an extremely difficult endeavor because it frequently results in incomplete or absent lipid modification. Previously, we identified a fusion sequence (D1) from a Neisseria meningitidis lipoprotein that induced a non-lipidated protein, E3 (the domain III of the dengue virus envelope protein), to become lipidated. However, without optimizing the growth conditions, some of the D1-fusion proteins were not lipidated. Here, we report the influence of medium components on the expression of recombinant lipoproteins in E. coli. For high-level expression of mature lipoproteins in the C43 (DE3) strain, M9 medium was better than M63 and the rich medium. Furthermore, we analyzed the influence of other media factors (including nitrogen and carbon sources, phosphate, ferrous ions, calcium, magnesium, and pH) on the levels of lipoprotein expression. The results showed that excess nitrogen sources and phosphate in M9 medium could increase the amount of immature lipoproteins, and glucose was a better carbon source than glycerol for expressing mature lipoproteins. We also found that lipoproteins tended to be completely processed in the alkaline environment, even in the nutrient-rich medium. Additional constructs expressing different immunogens or lipid signal peptides as targets were also utilized, demonstrating that these targets could be expressed as completely mature lipoproteins in the M9 medium but not in the rich medium. Our results provide the useful information for expressing mature exogenous lipoproteins in E. coli.

Vaginal Lactobacilli Reduce Neisseria gonorrhoeae Viability through Multiple Strategies: An in Vitro Study

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Claudio Foschi

2017-12-01

Full Text Available The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae (GC underline the need of “antibiotic-free” strategies for the control of gonorrhea. The aim of this study was to assess the anti-gonococcal activity of 14 vaginal Lactobacillus strains, belonging to different species (L. crispatus, L. gasseri, L. vaginalis, isolated from healthy pre-menopausal women. In particular, we performed “inhibition” experiments, evaluating the ability of both lactobacilli cells and culture supernatants in reducing GC viability, at two different contact times (7 and 60 min. First, we found that the acidic environment, associated to lactobacilli metabolism, is extremely effective in counteracting GC growth, in a pH- and time-dependent manner. Indeed, a complete abolishment of GC viability by lactobacilli supernatants was observed only for pH values < 4.0, even at short contact times. On the contrary, for higher pH values, no 100%-reduction of GC growth was reached at any contact time. Experiments with organic/inorganic acid solutions confirmed the strict correlation between the pH levels and the anti-gonococcal effect. In this context, the presence of lactate seemed to be crucial for the anti-gonococcal activity, especially for pH values in the range 4.4–5.3, indicating that the presence of H+ ions is necessary but not sufficient to kill gonococci. Moreover, experiments with buffered supernatants led to exclude a direct role in the GC killing by other bioactive molecules produced by lactobacilli. Second, we noticed that lactobacilli cells are able to reduce GC viability and to co-aggregate with gonococci. In this context, we demonstrated that released-surface components with biosurfactant properties, isolated from “highly-aggregating” lactobacilli, could affect GC viability. The antimicrobial potential of biosurfactants isolated from lactobacilli against pathogens has been largely investigated, but this is the first report about a

Comparison Predominant Oral micro-flora in Subjects with and without Complete Denture Referred to Yazd Dentistry Department

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Abbas Ali Jafari

2014-11-01

Results: The non-aureus staphylococcus and alpha-hemolytic streptococci showed the highest positive culture among the isolated microorganisms in both groups, whereas beta hemolytic streptococci showed the least percent of isolated microorganism in both groups. The higher density of non-aureus Staphylococci, α-hemolitic Streptococci, Gram negative cocobasillus, non-pathogenic Neisseria, Candida and Corynebacterium were recovered from oral samples of denture users in compare with dentate subjects (P= 0.0001. There was also seen a statistical significant correlation between the number of isolated microorganisms and the duration of denture utilization in denture users (P=0.013. Conclusion: Results of the present study showed that complete denture can be act as a predisposal factor in overgrowing of several oral micro-flora particularly Candida, non-aureus Staphylococci, α-hemolytic streptococci, gram negative cocobacillus, non-pathogenic Neisseria, and Corynebacterium, which emphasized the users denture hygine.

Type I interferon induction by Neisseria gonorrhoeae: Dual requirement of cyclic GMP-AMP synthase and Toll-like receptor 4

OpenAIRE

Andrade, Warrison A.; Agarwal, Sarika; Mo, Shunyan; Shaffer, Scott A.; Dillard, Joseph P.; Schmidt, Tobias; Hornung, Veit; Fitzgerald, Katherine A.; Kurt-Jones, Evelyn A.; Golenbock, Douglas T.

2016-01-01

The innate immune system is the first line of defense against Neisseria gonorrhoeae (GC). Exposure of cells to GC lipooligosaccharides induces a strong immune response, leading to type I interferon (IFN) production via TLR4/MD-2. In addition to living freely in the extracellular space, GC can invade the cytoplasm to evade detection and elimination. Double-stranded DNA introduced into the cytosol binds and activates the enzyme cyclic-GMP-AMP synthase (cGAS), which produces 2′3′-cGAMP and trigg...

Type III methyltransferase M.NgoAX from Neisseria gonorrhoeae FA1090 regulates biofilm formation and human cell invasion

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Agnieszka eKwiatek

2015-12-01

Full Text Available Neisseria gonorrhoeae is the etiological factor of the sexually transmitted gonorrhea disease that may lead, under specific conditions, to systemic infections. The gonococcal genome encodes many Restriction Modification (RM systems, which main biological role is to defend the pathogen from potentially harmful foreign DNA. However, RM systems seem also to be involved in several other functions. In this study, we examined the effect of inactivation the N. gonorrhoeae FA1090 ngo0545 gene encoding M.NgoAX methyltransferase on the global gene expression, biofilm formation, interactions with human epithelial host cells and overall bacterial growth. Expression microarrays showed at least a two-fold deregulation of a total of 121 genes in the NgoAX knock-out mutant compared to the wt strain under standard grow conditions. As determined by the assay with crystal violet, the NgoAX knock-out strain formed a slightly larger biofilm biomass per cell than the wt strain (OD570/600 = 13.8  2.24 and 9.35  2.06, respectively. SCLM observations showed that the biofilm formed by the gonococcal ngo0545 gene mutant is more relaxed and dispersed than the one formed by the wt strain. Thickness of the biofilm formed by both strains was 48.3 (14.9 µm for the mutant and 28.6 (4.0 µm for the wt. This more relaxed feature of the biofilm in respect to adhesion and bacterial interactions seems advantageous for pathogenesis of the NgoAX-deficient gonococci at the stage of human epithelial cell invasion. Indeed, the overall adhesion of mutant bacterial cells to human cells was lower than adhesion of the wt gonococci (adhesion index = 0.672 ( 0.2 and 2.15 ( 1.53, respectively; yet, a higher number of mutant than wt bacteria were found inside the Hec-1-B epithelial cells (invasion index = 3.38 ( 0.93  105 for mutant and 4.67 ( 3.09  104 for the wt strain. These results indicate that NgoAX-deficient cells have lower ability to attach to human cells

Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection.

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Oliver Kepp

2009-03-01

Full Text Available Bcl-2 family proteins including the pro-apoptotic BH3-only proteins are central regulators of apoptotic cell death. Here we show by a focused siRNA miniscreen that the synergistic action of the BH3-only proteins Bim and Bmf is required for apoptosis induced by infection with Neisseria gonorrhoeae (Ngo. While Bim and Bmf were associated with the cytoskeleton of healthy cells, they both were released upon Ngo infection. Loss of Bim and Bmf from the cytoskeleton fraction required the activation of Jun-N-terminal kinase-1 (JNK-1, which in turn depended on Rac-1. Depletion and inhibition of Rac-1, JNK-1, Bim, or Bmf prevented the activation of Bak and Bax and the subsequent activation of caspases. Apoptosis could be reconstituted in Bim-depleted and Bmf-depleted cells by additional silencing of antiapoptotic Mcl-1 and Bcl-X(L, respectively. Our data indicate a synergistic role for both cytoskeletal-associated BH3-only proteins, Bim, and Bmf, in an apoptotic pathway leading to the clearance of Ngo-infected cells.

Male non-gonococcal urethritis: From microbiological etiologies to demographic and clinical features.

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Ito, Shin; Hanaoka, Nozomu; Shimuta, Ken; Seike, Kensaku; Tsuchiya, Tomohiro; Yasuda, Mitsuru; Yokoi, Shigeaki; Nakano, Masahiro; Ohnishi, Makoto; Deguchi, Takashi

2016-04-01

To detect microorganisms responsible for male acute urethritis and to define the microbiology of non-gonococcal urethritis. The present study comprised 424 men with symptoms and signs compatible with acute urethritis. Their urethral swabs and first-voided urine underwent detection of the microorganisms. Demographic characteristics and clinical features of Mycoplasma genitalium-, Ureaplasma urealyticum-, Haemophilus influenza-, adenovirus- or Herpes simplex virus-positive monomicrobial non-gonococcal urethritis, or all-examined microorganism-negative urethritis in heterosexual men were compared with urethritis positive only for Chlamydia trachomatis. Neisseria gonorrhoeae was detected in 127 men (30.0%). In 297 men with non-gonococcal urethritis, C. trachomatis was detected in 143 (48.1%). In 154 men with non-chlamydial non-gonococcal urethritis, M. genitalium (22.7%), M. hominis (5.8%), Ureaplasma parvum (9.1%), U. urealyticum (19.5%), H. influenzae (14.3%), Neisseria meningitidis (3.9%), Trichomonas vaginalis (1.3%), human adenovirus (16.2%), and Herpes simplex virus types 1 (7.1%) and 2 (2.6%) were detected. Although some features of monomicrobial non-chlamydial non-gonococcal urethritis or all-examined microorganism-negative urethritis were significantly different from those of monomicrobial chlamydial non-gonococcal urethritis, most features were superimposed. Predicting causative microorganisms in men with non-gonococcal urethritis based on demographic and clinical features is difficult. However, the present study provides useful information to better understand the microbiological diversity in non-gonococcal urethritis, and to manage patients with non-gonococcal urethritis appropriately. © 2016 The Japanese Urological Association.

Trends in the prevalence of pathogens causing urethritis in Asturias, Spain, 1989-2000.

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Varela, José A; Otero, Luis; García, María José; Palacio, Virgilo; Carreño, Francisco; Cuesta, Mar; Sánchez, Carmen; Vázquez, Fernando

2003-04-01

There are few studies of recent trends in the etiology and epidemiologic characteristics of specific microorganisms causing urethritis in men. The objective of the current study was to show the clinical experience in our country and to evaluate the trends in the prevalence of the pathogens in male urethritis, as well as the epidemiologic patterns in a series of 2101 patients. This was a descriptive study of the etiological agents causing urethritis in our sexually transmitted disease clinics in a period of 12 years (1989-2000), with a comparison of two periods of time. There were 97 cases of gonococcal urethritis (4.6%), 2004 of nongonococcal urethritis (95.4%), and 82 of mixed urethritis (3.9%). An association was found between gonococcal urethritis and heterosexual men; between chlamydial urethritis and homosexual/bisexual men; Ureaplasma urealyticum urethritis and heterosexual men and patients younger than 30 years of age; and between trichomonal urethritis and patients more than 30 years of age and the presence of HIV antibodies. During the period of research there was a significant decrease in cases of Neisseria gonorrhoeae and Chlamydia trachomatis urethritis and an increase in those of U urealyticum urethritis. In conclusion, this report describes changes in the etiology and epidemiologic patterns of urethritis in our country in recent years.

Prevalencia de anticuerpos anti-Chlamydia trachomatis y anti-Neisseria gonorrhoeae en grupos de individuos de la población mexicana Prevalence of antibodies against Chlamydia trachomatis and Neisseria gonorrhoeae in Mexican populations

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María del Carmen Cravioto

2003-01-01

Full Text Available OBJETIVO: Estimar la prevalencia de infección por Chlamydia trachomatis (CT y Neisseria gonorrhoeae (NG en grupos de individuos con diferente riesgo para infecciones de transmisión sexual. MATERIAL Y MÉTODOS: Estudio transversal multicéntrico efectuado en el Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, de la Ciudad de México, de enero de 1992 a diciembre de 1993, en el que se estudiaron 945 individuos en edad reproductiva, 585 mujeres y 360 hombres. Según su riesgo para infecciones de transmisión sexual se clasificaron en grupos de alto y bajo riesgo. Los de alto riesgo incluyeron mujeres infértiles con daño tubario, mujeres con embarazo ectópico o aborto, hombres infértiles, pacientes con VIH/SIDA, hombres homo o bisexuales y trabajadoras del sexo comercial (TSC. Los de bajo riesgo: mujeres primigestas, hombres fértiles y mujeres infértiles sin daño tubario. Se determinó en duplicado IgG e IgA anti-NG y anti-CT en suero, por análisis inmunoenzimático, utilizando como antígeno el pili de NG y la fracción L1 de CT. Se calcularon porcentajes. RESULTADOS: En mujeres la prevalencia para NG fue IgG 13.7% e IgA 14.3%, y para CT fue IgG 11.4% e IgA 4.4%. En hombres, NG 3.3% y 13.3%, respectivamente, y para CT 7.2% y 5.5%, respectivamente. En TSC se encontró NG en 31.2 % y 28.4%, respectivamente, y para CT 25.0% y 5.7%, respectivamente. En mujeres con infertilidad por daño tubario, NG 5.6% y 9.8%, respectivamente, y CT 8.4% y 1.4%, respectivamente. En 110 primigestas jóvenes, NG 4.5% y 10.0%, respectivamente, y CT 3.6% y 9.1%, respectivamente. CONCLUSIONES: Estos datos confirman la prevalencia elevada de Neisseria gonorrhoeae y Chlamydia trachomatis en trabajadoras del sexo comercial y en hombres homo/bisexuales, pero no en otros grupos de alto riesgo como las mujeres infértiles, con aborto o embarazo ectópico.OBJECTIVE: To estimate the prevalence of Chlamydia trachomatis (CT and Neisseria gonorrhoeae

Molecular properties of bacterial multidrug transporters

NARCIS (Netherlands)

Putman, M; van Veen, HW; Konings, WN

2000-01-01

One of the mechanisms that bacteria utilize to evade the toxic effects of antibiotics is the active extrusion of structurally unrelated drugs from the cell. Both intrinsic and acquired multidrug transporters play an important role in antibiotic resistance of several pathogens, including Neisseria