Ditmyer, Heidi; Craig, Linden
Canine blastomycosis is a common systemic fungal infection within the Ohio and Mississippi River valleys and typically presents as pneumonia, lymphadenitis, or endophthalmitis. This report describes three cases in which mammary tissue samples were submitted to the Department of Pathobiology, University of Tennessee, College of Veterinary Medicine with clinical suspicion of neoplasia or postpartum bacterial mastitis. Pyogranulomatous to granulomatous mastitis and dermatitis with intralesional yeast consistent with Blastomyces dermatitidis were diagnosed. Two of the three dogs also had lymph node and pulmonary involvement. Mycotic mastitis due to Blastomyces dermatitidis is rarely reported and blastomycosis should be considered in the differential diagnosis of dogs with mammary lesions from endemic areas.
Nemeth, Nicole M; Campbell, G Douglas; Oesterle, Paul T; Shirose, Lenny; McEwen, Beverly; Jardine, Claire M
Blastomyces dermatitidis, a fungus that can cause fatal infection in humans and other mammals, is not readily recoverable from soil, its environmental reservoir. Because of the red fox's widespread distribution, susceptibility to B. dermatitidis, close association with soil, and well-defined home ranges, this animal has potential utility as a sentinel for this fungus.
Muñoz, José F.; Gauthier, Gregory M.; Desjardins, Christopher A.; Gallo, Juan E.; Holder, Jason; Sullivan, Thomas D.; Marty, Amber J.; Carmen, John C.; Chen, Zehua; Ding, Li; Gujja, Sharvari; Magrini, Vincent; Misas, Elizabeth; Mitreva, Makedonka; Priest, Margaret
Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated...
Elizabeth M Brown
Full Text Available Analysis of the population genetic structure of microbial species is of fundamental importance to many scientific disciplines because it can identify cryptic species, reveal reproductive mode, and elucidate processes that contribute to pathogen evolution. Here, we examined the population genetic structure and geographic differentiation of the sexual, dimorphic fungus Blastomyces dermatitidis, the causative agent of blastomycosis.Criteria for Genealogical Concordance Phylogenetic Species Recognition (GCPSR applied to seven nuclear loci (arf6, chs2, drk1, fads, pyrF, tub1, and its-2 from 78 clinical and environmental isolates identified two previously unrecognized phylogenetic species. Four of seven single gene phylogenies examined (chs2, drk1, pyrF, and its-2 supported the separation of Phylogenetic Species 1 (PS1 and Phylogenetic Species 2 (PS2 which were also well differentiated in the concatenated chs2-drk1-fads-pyrF-tub1-arf6-its2 genealogy with all isolates falling into one of two evolutionarily independent lineages. Phylogenetic species were genetically distinct with interspecific divergence 4-fold greater than intraspecific divergence and a high Fst value (0.772, P<0.001 indicative of restricted gene flow between PS1 and PS2. Whereas panmixia expected of a single freely recombining population was not observed, recombination was detected when PS1 and PS2 were assessed separately, suggesting reproductive isolation. Random mating among PS1 isolates, which were distributed across North America, was only detected after partitioning isolates into six geographic regions. The PS2 population, found predominantly in the hyper-endemic regions of northwestern Ontario, Wisconsin, and Minnesota, contained a substantial clonal component with random mating detected only among unique genotypes in the population.These analyses provide evidence for a genetically divergent clade within Blastomyces dermatitidis, which we use to describe a novel species
José F Muñoz
Full Text Available Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics
Muñoz, José F; Gauthier, Gregory M; Desjardins, Christopher A; Gallo, Juan E; Holder, Jason; Sullivan, Thomas D; Marty, Amber J; Carmen, John C; Chen, Zehua; Ding, Li; Gujja, Sharvari; Magrini, Vincent; Misas, Elizabeth; Mitreva, Makedonka; Priest, Margaret; Saif, Sakina; Whiston, Emily A; Young, Sarah; Zeng, Qiandong; Goldman, William E; Mardis, Elaine R; Taylor, John W; McEwen, Juan G; Clay, Oliver K; Klein, Bruce S; Cuomo, Christina A
Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics of genome evolution
Reed, Kurt D.; Meece, Jennifer K.; Archer, John R.; Peterson, A. Townsend
Background Blastomycosis is a potentially fatal mycosis that is acquired by inhaling infectious spores of Blastomyces dermatitidis present in the environment. The ecology of this pathogen is poorly understood, in part because it has been extremely difficult to identify the niche(s) it occupies based on culture isolation of the organism from environmental samples. Methodology/Principal Findings We investigated the ecology of blastomycosis by performing maximum entropy modeling of exposure sites from 156 cases of human and canine blastomycosis to provide a regional-scale perspective of the geographic and ecologic distribution of B. dermatitidis in Wisconsin. Based on analysis with climatic, topographic, surface reflectance and other environmental variables, we predicted that ecologic conditions favorable for maintaining the fungus in nature occur predominantly within northern counties and counties along the western shoreline of Lake Michigan. Areas of highest predicted occurrence were often in proximity to waterways, especially in northcentral Wisconsin, where incidence of infection is highest. Ecologic conditions suitable for B. dermatitidis are present in urban and rural environments, and may differ at the extremes of distribution of the species in the state. Conclusions/Significance Our results provide a framework for a more informed search for specific environmental factors modulating B. dermatitidis occurrence and transmission and will be useful for improving public health awareness of relative exposure risks. PMID:18446224
Walkty, Andrew; Keynan, Yoav; Karlowsky, James; Dhaliwal, Perry; Embil, John
Blastomyces dermatitidis is a thermally dimorphic fungus that is capable of causing pulmonary and extra-pulmonary disease, including infections of the central nervous system (CNS). Diagnosis of CNS blastomycosis with non-invasive testing can be difficult, and a surgical biopsy may ultimately be required for microbiological and/or histopathological confirmation. A case of B. dermatitidis meningitis is presented where the diagnosis was made by testing cerebrospinal fluid (CSF) using the MVista® Blastomyces Quantitative Antigen Enzyme Immunoassay test. The utility of performing this test on CSF for diagnosis of CNS mass lesions/abscesses caused by B. dermatitidis in the absence of associated meningitis remains unclear. Cross reaction of the Blastomyces antigen test with other dimorphic fungi is a concern, necessitating that positive test results are interpreted in the context of the patient's exposure and travel history. Copyright © 2017 Elsevier Inc. All rights reserved.
Meece, Jennifer K.; Anderson, Jennifer L.; Gruszka, Sarah; Sloss, Brian L.; Sullivan, Bradley; Reed, Kurt D.
Background. Blastomyces dermatitidis, the etiologic agent of blastomycosis, has 2 genetic groups and shows varied clinical presentation, ranging from silent infections to fulminant respiratory disease and dissemination. The objective of this study was to determine whether clinical phenotype and outcomes vary based on the infecting organism's genetic group.Methods. We used microsatellites to genotype 227 clinical isolates of B. dermatitidis from Wisconsin patients. For each isolate, corresponding clinical disease characteristics and patient demographic information were abstracted from electronic health records and Wisconsin Division of Health reportable disease forms and questionnaires.Results. In univariate analysis, group 1 isolates were more likely to be associated with pulmonary-only infections (P 1 month (P smoking status (P = .0001) remained predictors for group 2 infections.Conclusions. This study identified previously unknown associations between clinical phenotype of human infection and genetic groups of B. dermatitidis and provides a framework for further investigations of the genetic basis for virulence in B. dermatitidis.
Amber J Marty
Full Text Available In response to temperature, Blastomyces dermatitidis converts between yeast and mold forms. Knowledge of the mechanism(s underlying this response to temperature remains limited. In B. dermatitidis, we identified a GATA transcription factor, SREB, important for the transition to mold. Null mutants (SREBΔ fail to fully complete the conversion to mold and cannot properly regulate siderophore biosynthesis. To capture the transcriptional response regulated by SREB early in the phase transition (0-48 hours, gene expression microarrays were used to compare SREB∆ to an isogenic wild type isolate. Analysis of the time course microarray data demonstrated SREB functioned as a transcriptional regulator at 37°C and 22°C. Bioinformatic and biochemical analyses indicated SREB was involved in diverse biological processes including iron homeostasis, biosynthesis of triacylglycerol and ergosterol, and lipid droplet formation. Integration of microarray data, bioinformatics, and chromatin immunoprecipitation identified a subset of genes directly bound and regulated by SREB in vivo in yeast (37°C and during the phase transition to mold (22°C. This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation. Functional analysis suggested that lipid droplets were actively metabolized during the phase transition and lipid metabolism may contribute to filamentous growth at 22°C. Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX. Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition.
Marty, Amber J; Wüthrich, Marcel; Carmen, John C; Sullivan, Thomas D; Klein, Bruce S; Cuomo, Christina A; Gauthier, Gregory M
Blastomyces dermatitidis belongs to a group of thermally dimorphic fungi that grow as sporulating mold in the soil and convert to pathogenic yeast in the lung following inhalation of spores. Knowledge about the molecular events important for fungal adaptation and survival in the host remains limited. The development of high-throughput analytic tools such as RNA sequencing (RNA-Seq) has potential to provide novel insight on fungal pathogenesis especially if applied in vivo during infection. However, in vivo transcriptional profiling is hindered by the low abundance of fungal cells relative to mammalian tissue and difficulty in isolating fungal cells from the tissues they infect. For the purpose of obtaining B. dermatitidis RNA for in vivo transcriptional analysis by RNA-Seq, we developed a simple technique for isolating yeast from murine lung tissue. Using a two-step approach of filtration and centrifugation following lysis of murine lung cells, 91% of yeast cells causing infection were isolated from lung tissue. B. dermatitidis recovered from the lung yielded high-quality RNA with minimal murine contamination and was suitable for RNA-Seq. Approximately 87% of the sequencing reads obtained from the recovered yeast aligned with the B. dermatitidis genome. This was similar to 93% alignment for yeast grown in vitro. The use of near-freezing temperature along with short ex vivo time minimized transcriptional changes that would have otherwise occurred with higher temperature or longer processing time. In conclusion, we have developed a technique that recovers the majority of yeast causing pulmonary infection and yields high-quality fungal RNA with minimal contamination by mammalian RNA. Copyright © 2013 Elsevier Inc. All rights reserved.
Marty, Amber J; Gauthier, Gregory M
Blastomyces dermatitidis, the etiologic agent of blastomycosis, belongs to a group of thermally dimorphic fungi that change between mold (22°C) and yeast (37°C) in response to temperature. The contribution of structural proteins such as septins to this phase transition in these fungi remains poorly understood. Septins are GTPases that serve as a scaffold for proteins involved with cytokinesis, cell polarity, and cell morphology. In this study, we use a GFP sentinel RNA interference system to investigate the impact of CDC3, CDC10, CDC12, and ASPE on the morphology and phase transition of B. dermatitidis. Targeting CDC3, CDC10, and CDC12 by RNA interference resulted in yeast with aberrant morphology at 37°C with defects in cytokinesis. Downshifting the temperature to 22°C promoted the conversion to the mold phase, but did not abrogate the morphologic defects. CDC3, CDC10, and CDC12 knockdown strains grew as mold with curved, thickened hyphae. Knocking down ASPE transcript did not alter morphology of yeast at 37°C or mold at 22°C. Following an increase in temperature from 22°C to 37°C, all septin knockdown strains were able to revert to yeast. In conclusion, CDC3, CDC10, and CDC12 septin- encoding genes are required for proper morphology of yeast and hyphae, but are dispensable for the phase transition.
Klein, B.S.; Jones, J.M.
No well-defined Blastomyces-specific antigens are currently available. We used sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting to identify immunologically active molecules in the cell wall of B. dermatitidis. A major immunoreactive 120-kD protein (WI-1) was present in all five strains studied and comprised 5% of the protein in the cell wall extract obtained after freezing and thawing yeast cells. WI-1 was recognized by serum from all 10 patients with blastomycosis but by none of those from 5 patients with histoplasmosis. It was purified by electroelution, radiolabeled with 125I, and incorporated into a radioimmunoassay (RIA) for serodiagnosis of blastomycosis. Antibody to WI-1 was detected in 58 (85%) of 68 patients with blastomycosis (geometric mean titer, 1:2,981), in two (3%) of 73 patients with histoplasmosis, coccidioidomycosis, sporotrichosis, or candidiasis (titers, 1:86 and 1:91) and in none of 44 healthy persons. WI-1 was shown to be a surface molecule abundant on B. dermatitidis yeasts that were indirectly stained with serum from a rabbit immunized with WI-1. Approximately 0.93 pg of WI-1 or 4.7 x 10(6) WI-1 molecules were found on the surface of an individual yeast using an antigen-inhibition RIA; none was found on Histoplasma capsulatum or Candida albicans yeasts. We conclude that WI-1 is a novel, immunologically active surface molecule on the invasive form of B. dermatitidis and that WI-1 can be used to reliably detect antibody and study the immunopathogenesis of blastomycosis
Klein, B.S.; Jones, J.M.
No well-defined Blastomyces-specific antigens are currently available. We used sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting to identify immunologically active molecules in the cell wall of B. dermatitidis. A major immunoreactive 120-kD protein (WI-1) was present in all five strains studied and comprised 5% of the protein in the cell wall extract obtained after freezing and thawing yeast cells. WI-1 was recognized by serum from all 10 patients with blastomycosis but by none of those from 5 patients with histoplasmosis. It was purified by electroelution, radiolabeled with 125I, and incorporated into a radioimmunoassay (RIA) for serodiagnosis of blastomycosis. Antibody to WI-1 was detected in 58 (85%) of 68 patients with blastomycosis (geometric mean titer, 1:2,981), in two (3%) of 73 patients with histoplasmosis, coccidioidomycosis, sporotrichosis, or candidiasis (titers, 1:86 and 1:91) and in none of 44 healthy persons. WI-1 was shown to be a surface molecule abundant on B. dermatitidis yeasts that were indirectly stained with serum from a rabbit immunized with WI-1. Approximately 0.93 pg of WI-1 or 4.7 x 10(6) WI-1 molecules were found on the surface of an individual yeast using an antigen-inhibition RIA; none was found on Histoplasma capsulatum or Candida albicans yeasts. We conclude that WI-1 is a novel, immunologically active surface molecule on the invasive form of B. dermatitidis and that WI-1 can be used to reliably detect antibody and study the immunopathogenesis of blastomycosis.
compatibility in cross-mating experiments. The diagnosis of this disease can be ... The kidney and prostate are other organs commonly involved. In the lung, the disease process may be acute or chronic, the latter presenting in a similar fashion to ...
Marty, Amber J.; Wüthrich, Marcel; Carmen, John C.; Sullivan, Thomas D.; Klein, Bruce S.; Cuomo, Christina A.; Gauthier, Gregory M.
B. dermatitidis belongs to a group of thermally dimorphic fungi that grow as sporulating mold in the soil and convert to pathogenic yeast in the lung following inhalation of spores. Knowledge about the molecular events important for fungal adaptation and survival in the host remains limited. The development of high-throughput analytic tools such as RNA sequencing (RNA-Seq) has potential to provide novel insight on fungal pathogenesis especially if applied in vivo during infection. However, in...
Woods, Katharine S; Barry, Maureen; Richardson, Danielle
A 6-month-old male castrated Labrador retriever was presented for coughing and forelimb lameness. Blastomyces dermatitidis was identified in cytology of sputum and synovial fluid. Repeat arthrocentesis 7 months later revealed resolution of septic arthritis. Fungal septic arthritis should be considered for cases of monoarthritis and may respond to oral itraconazole treatment.
Woods, Katharine S.; Barry, Maureen; Richardson, Danielle
A 6-month-old male castrated Labrador retriever was presented for coughing and forelimb lameness. Blastomyces dermatitidis was identified in cytology of sputum and synovial fluid. Repeat arthrocentesis 7 months later revealed resolution of septic arthritis. Fungal septic arthritis should be considered for cases of monoarthritis and may respond to oral itraconazole treatment.
Hernández Tapia, Ana Laura; Santoscoy Mejía, Eduardo Carlos; Ramírez Lezama, José; Cervantes Olivares, Roberto A.; Quiroz Mercado, Joaquín Arturo
La infección del sistema nervioso en el perro es poco común; posibles causas son Aspergillus spp, Cryptococcus neoformans, Blastomyces dermatidis y Coccidioides immitis. La infección por Aspergillus spp afecta al aparato respiratorio y en pocas ocasiones se presenta de manera diseminada. Sin embargo, en el Pastor Alemán hay mayor incidencia de éste, pues dicha infección se asocia con una deficiencia inmunológica. Se describe el caso de una perra de raza Pastor Alemán, de 1.5 años de edad, ref...
Associação da rifampicina à anfotericina B no tratamento da paracoccidioidomicose: resultados em três pacientes tratados Association of Amphotericin B and Rifampicin in the treatment of paracoccidioidomycosis. Report of efficacy in three cases
Full Text Available Trabalhos experimentais demonstraram que a anfotericina B, desorganizando funcionalmente a membrana celular fúngica, permite a penetração da rifampicina no citoplasma e sua conseqüente ação contra Histoplasma capsulatum, Blastomyces dermatitidis e Candida albicans. Com metade das doses habituais' de anfotericina B associada à rifampicina conseguem-se melhores resultados do que com a anfotericina B isoladamente em doses plenas. Os Autores discutem as possíveis aplicações desta associação no tratamento da paracoccidioidomi-cose e apresentam 3 casos desta micose em que a inatividade clínica e micológica só foi obtida após o emprego combinado destas drogas.Experimental data have shown that low concentration of amphotericin B disrupts of the fungal cellular membranes, enhancing entrance of rifampicin into citoplasm, where it acts specifically as an antifungal agent against Histoplasma capsulatum, Blastomyces dermatitidis and Candida albicans. Amphotericin B in half dosage combined with rifampicin is more effective than when used alone in full dosage. The Authors discuss the possible indications of this association in the therapy of paracoccidioidomycosis, and report its efficacy in three cases of this disease only controlled after its use.
Reynolds, Daniel J; Andersen, Carl A; Hoskote, Sumedh S; Lee, Hee Eun; Raghunathan, Aditya; Kalra, Sanjay; Limper, Andrew H
A 19-year-old male with a history of idiopathic panuveitis, currently taking methotrexate and infliximab, presented to our institution with 6 weeks of cough, dyspnoea and fevers. He had failed outpatient antimicrobial therapy. Computerised tomography (CT) of the chest revealed the presence of a lobar pneumonia and he was treated with broad spectrum antibiotics, which did not improve his symptoms. Bronchoalveolar lavage was performed with a transbronchial lung biopsy because of the diagnostic uncertainty of the patient's presentation. Pathology revealed non-budding yeasts, consistent with Pneumocystis Serological and urine studies were positive for both Histoplasma and Blastomyces The diagnosis of Histoplasma pneumonia was made because of the presentation being inconsistent with Pneumocystis pneumonia, and serology, urine and pathology testing being more consistent with Histoplasma The patient was treated with oral itraconazole and was doing well at follow-up 12 weeks after hospitalisation. © Royal College of Physicians 2016. All rights reserved.
KUROKAWA Cilmery Suemi
Full Text Available Pathogenic fungi that cause systemic mycoses retain several factors which allow their growth in adverse conditions provided by the host, leading to the establishment of the parasitic relationship and contributing to disease development. These factors are known as virulence factors which favor the infection process and the pathogenesis of the mycoses. The present study evaluates the virulence factors of pathogenic fungi such as Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis in terms of thermotolerance, dimorphism, capsule or cell wall components as well as enzyme production. Virulence factors favor fungal adhesion, colonization, dissemination and the ability to survive in hostile environments and elude the immune response mechanisms of the host. Both the virulence factors presented by different fungi and the defense mechanisms provided by the host require action and interaction of complex processes whose knowledge allows a better understanding of the pathogenesis of systemic mycoses.
Ryan R Kroll
Full Text Available In certain parts of the United States and Canada, and northern Ontario in particular, the dimorphic fungus Blastomyces dermatitidis is endemic and can cause infection in exposed individuals. The site of infection is usually pulmonary, causing respiratory and constitutional symptoms, but can also affect other sites in the body. Symptom severity can vary substantially from no symptoms to fatal acute respiratory distress syndrome. The present report describes a 27-year-old professional diver who had recently worked in northern Ontario, who developed symptoms of pneumonia and exhibited atypical findings on chest imaging. He was diagnosed with blastomycosis based on histopathological findings and fungal culture, and was treated with amphotericin B and itraconazole in accordance with treatment guidelines. While outdoor occupations in endemic areas increase the risk of infection, there is no literature specifically identifying professional diving as an occupational risk for blastomycosis.
Zarnowski, Robert; Woods, Jon P.
In this study, extracellular glutathione-dependent ferric reductase (GSH-FeR) activities in different dimorphic zoopathogenic fungal species were characterized. Supernatants from Blastomyces dermatitidis, Histoplasma capsulatum, Paracoccidioides brasiliensis and Sporothrix schenckii strains grown in their yeast form were able to reduce iron enzymically with glutathione as a cofactor. Some variations in the level of reduction were noted amongst the strains. This activity was stable in acidic, neutral and slightly alkaline environments and was inhibited when trivalent aluminium and gallium ions were present. Using zymography, single bands of GSH-FeRs with apparent molecular masses varying from 430 to 460 kDa were identified in all strains. The same molecular mass range was determined by size exclusion chromatography. These data demonstrate that dimorphic zoopathogenic fungi produce and secrete a family of similar GSH-FeRs that may be involved in the acquisition and utilization of iron. Siderophore production by these and other fungi has sometimes been considered to provide a full explanation of iron acquisition in these organisms. Our work reveals an additional common mechanism that may be biologically and pathogenically important. Furthermore, while some characteristics of these enzymes such as extracellular location, cofactor utilization and large size are not individually unique, when considered together and shared across a range of fungi, they represent an important novel physiological feature. PMID:16000713
Drouhet, E; Dupont, B
Forty-eight cases of deep mycoses were studied and treated with ketoconazole, each with in vitro evaluation of the minimum inhibitory concentrations (MIC) of the causative fungi, in vivo pharmacokinetic, clinical, and mycologic evaluations, several months to two years after the treatment was stopped. Excellent results were obtained in six cases of chronic mucocutaneous candidiasis, with restoration of immunologic disturbances; 23 cases of systemic candidiasis, including new aspects of heroin addicts with cutaneous, ocular, or osteoarticular manifestations; eight cases of histoplasmosis, five due to Histoplasma capsulatum and three to Histoplasma duboisii, with cure in seven and remission in one; one case of African blastomycosis (Blastomyces dermatitidis); three cases of mycetoma, two due to Monosporium apiospermum, one due to a dematiacious fungus; three cases of entomophthoromycosis with cure; one case of fungal arthritis, due to new hyphomycete similar to M. apiospermum, pathogenic for laboratory animals; one case of Drechslera longirostrata causing vertebral arthritis, following a fungal endocarditis and cured by combination of ketoconazole with amphotericin B, each agent alone being ineffective; and other deep mycoses.
Dixon, D M; Casadevall, A; Klein, B; Mendoza, L; Travassos, L; Deepe, G S
Vaccine approaches to infectious diseases are widely applied and appreciated. Disciplines such as bacteriology and virology have a rich history of successful vaccine development. The complexity of eukaryotic systems presents additional challenges to the development of vaccines against them. These challenges are being met in the fields of parasitology, and are being revisited for application in oncology. Vaccine opportunities exist in medical mycology. The National Institute of Allergy and Infectious Diseases has held a series of workshops in medical mycology where the need to develop vaccines for fungal diseases was noted and where important opportunities were discussed. Major advances in vaccinology and the technology of antigen preparation and delivery have increased feasibility and heightened interest. The recent epidemic of coccidioidomycosis in the American Southwest has demonstrated the need for developing a vaccine as an effective preventive measure for those living in and for those who subsequently move into regions with the endemic mycoses. The XIIth Congress of the International Society for Human and Animal Mycology included a symposium that summarized new vaccination strategies for selected fungi: Candida albicans, Coccidioides immitis, and Trichophyton verrucosum. The goal of the present summary is to provide representative examples of continuing efforts relating to vaccine development within the medical mycological community highlighting Blastomyces dermatidis, Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, and Pythiumn insidiosum.
Storms, Timothy N; Clyde, Victoria L; Munson, Linda; Ramsay, Edward C
Blastomycosis was diagnosed in six nondomestic felids from eastern Tennessee, including two Asian lions (Panthera leo persicus), one African lion (Panthera leo), one Siberian tiger (Panthera tigris), one cheetah (Acinonyx jubatus), and one snow leopard (Panthera uncia). Clinical signs included lethargy, anorexia, weight loss, dyspnea, sneezing. ataxia, and paresis. Variable nonspecific changes included leukocytosis, monocytosis, moderate left shift of neutrophils, moderate hypercalcemia, hyperproteinemia, and hyperglobulinemia. Thoracic radiographs revealed interstitial and alveolar changes, consolidation or collapse of a lung lobe, bullae formation, and a pulmonary mass. Agar gel immunodiffusion (AGID) serology for Blastomyces dermatitidis was performed in five felids and was positive in three. The tiger had cerebral blastomycosis and was positive for AGID serologic tests of both cerebrospinal fluid and serum. One percutaneous lung aspirate in the snow leopard and one bronchial aspirate in an Asian lion demonstrated B. dermatitidis organisms. whereas tracheal wash samples and a nasal discharge were nondiagnostic in others. Treatment with itraconazole was attempted in four cats. The tiger improved before euthanasia, whereas the others did not survive beyond initial treatments. In four felids, B. dermatitidis was found in the lungs and tracheobronchial lymph nodes associated with a florid pyogranulomatous reaction; the tiger had a pyogranulomatous encephalomyelitis, and the cheetah had a single pulmonary granuloma. Thoracic radiography, cytologic examination of lung lesion aspirates, and B. dermatitidis AGID serology should be performed on clinically ill zoo felids in endemic areas to rule out blastomycosis.
O Guinn, Devon J; Serletis, Demitre; Kazemi, Noojan
We present a rare case of thoracic vertebral osteomyelitis secondary to pulmonary Blastomyces dermatitides. A 27-year-old male presented with three months of chest pains and non-productive cough. Examination revealed diminished breath sounds on the right. CT/MR imaging confirmed a right-sided pre-/paravertebral soft tissue mass and destructive lytic lesions from T2 to T6. CT-guided needle biopsy confirmed granulomatous pulmonary Blastomycosis. Conservative management with antifungal therapy was initiated. Neurosurgical review confirmed no clinical or profound radiographic instability, and the patient was stabilized with TLSO bracing. Serial imaging 3 months later revealed near-resolution of the thoracic soft tissue mass, with vertebral re-ossification from T2 to T6. Fungal osteomyelitis presents a rare entity in the spectrum of spinal infections. In such cases, lytic spinal lesions are classically seen in association with a large paraspinous mass. Fungal infections of the spinal column may be treated conservatively, with surgical intervention reserved for progressive cases manifesting with neurological compromise and/or spinal column instability. Here, we found unexpected evidence for vertebral re-ossification across the affected thoracic levels (T2-6) in response to IV antibiotic therapy and conservative bracing, nearly 3 months later. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Chitko-McKown, C G; Leymaster, K A; Heaton, M P; Griffin, D D; Veatch, J K; Jones, S A; Clawson, M L
An 8-month-old crossbred ewe, normal upon physical examination, was humanely euthanized for tissue collection. After approximately 3 weeks in tissue culture, fungi began budding out of cells obtained from the choroid plexus. After an additional 3 weeks, budding was observed in kidney cell cultures and eventually in monocyte cultures as well. Serum from the lamb was submitted to the Veterinary Diagnostic Laboratory at Colorado State University for fungal diagnosis and was found negative for Aspergillus, Blastomyces, Coccidioidomycosis and Histoplasmosis. DNA was isolated from fungi collected from tissue culture supernatants and used in a set of pan-fungal PCR assays with DNA from Candida acting as a positive control. PCR products were sequenced and BLAST analysis performed. The unknown fungal sequence aligned with 100% identity to Rhodotorula minuta an emerging opportunistic pathogen. Samples were submitted to The Fungal Testing Laboratory at The University of Texas Health Science Center at San Antonio for additional validation. We believe this to be the first report of Rhodotorula fungemia in a sheep in the United States. © 2013 Blackwell Verlag GmbH.
Ito, Hitoshi; Ishigaki, Isao
Radiation treatment is getting important position for sterilizing medical devices and for packaging films of foods. Recently, survey of bioburden is an important technique for evaluation of sterility doses for medical devices. However, many studies have been done mainly on the irradiation effects of spore-forming bacteria in medical devices. In this study, radiation sensitivity of spore-forming bacteria and fungi were examined after the survey on distribution of microorganisms in several kinds of medical devices. The main contaminant in disposable syringes, needles and conical flasks were consisted of Bacillus, with lesser amount of Micrococcus, Pseudomonas, Peptococcaceae and fungi as positive of 5 - 60 % in the medical devices which cultivated in thioglycolate broth. Bacillus group were identified as B. pumilus, B. sphaericus, B. coagulans, B. megaterium and etc. Fungi were isolated a lesser amounts compared with spore-forming bacteria and identified as Blastomyces, Penicillium, Haplosporangium, Euricoa and Audeobasidium. Peptococaceae were not isolated after irradiation with a dose of 0.1 Mrad even the samples were contaminated with high percentage. The D 10 values of dryed endospores of Bacillus-isolates which attached to the filter paper with pepton-glycerin were obtained to be 0.11 - 0.19 Mrad. The D 10 values of many isolates of fungi in dry condition were obtained below 0.08 Mrad. However, the isolate of Aureobasidium is radiation-resistant, and it's D 10 values was obtained as 0.28 Mrad under aerobic and anaerobic dry condition. (author)
Reilly, Thomas J; Calcutt, Michael J; Wennerdahl, Laura A; Williams, Fred; Evans, Tim J; Ganjam, Irene K; Bowman, Jesse W; Fales, William H
Microbiological and histological analysis of a sample from a swollen testicle of a 2-year-old Border Collie dog revealed a mixed infection of the fungus Blastomyces dermatitidis and the Gram-negative bacterium Aureimonas altamirensis. When subjected to an automated microbial identification system, the latter isolate was provisionally identified as Psychrobacter phenylpyruvicus, but the organism shared several biochemical features with Brucella canis and exhibited agglutination, albeit weakly, with anti-B. canis antiserum. Unequivocal identification of the organism was only achieved by 16S ribosomal RNA gene sequencing, ultimately establishing the identity as A. altamirensis. Since its first description in 2006, this organism has been isolated infrequently from human clinical samples, but, to the authors' knowledge, has not been reported from a veterinary clinical sample. While of unknown clinical significance with respect to the pathology observed for the polymicrobial infection described herein, it highlights the critical importance to unambiguously identify the microbe for diagnostic, epidemiological, infection control, and public health purposes. © 2014 The Author(s).
Boyce, Kylie J; Andrianopoulos, Alex
The ability of pathogenic fungi to switch between a multicellular hyphal and unicellular yeast growth form is a tightly regulated process known as dimorphic switching. Dimorphic switching requires the fungus to sense and respond to the host environment and is essential for pathogenicity. This review will focus on the role of dimorphism in fungi commonly called thermally dimorphic fungi, which switch to a yeast growth form during infection. This group of phylogenetically diverse ascomycetes includes Talaromyces marneffei (recently renamed from Penicillium marneffei), Blastomyces dermatitidis (teleomorph Ajellomyces dermatitidis), Coccidioides species (C. immitis and C. posadasii), Histoplasma capsulatum (teleomorph Ajellomyces capsulatum), Paracoccidioides species (P. brasiliensis and P. lutzii) and Sporothrix schenckii (teleomorph Ophiostoma schenckii). This review will explore both the signalling pathways regulating the morphological transition and the transcriptional responses necessary for intracellular growth. The physiological requirements of yeast cells during infection will also be discussed, highlighting recent advances in the understanding of the role of iron and calcium acquisition during infection. © FEMS 2015. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Laura Elena Carreto-Binaghi
Full Text Available Healthcare-associated infections (HAI are described in diverse settings. The main etiologic agents of HAI are bacteria (85% and fungi (13%. Some factors increase the risk for HAI, particularly the use of medical devices; patients with severe cuts, wounds, and burns; stays in the intensive care unit, surgery, and hospital reconstruction works. Several fungal HAI are caused by Candida spp., usually from an endogenous source; however, cross-transmission via the hands of healthcare workers or contaminated devices can occur. Although other medically important fungi, such as Blastomyces dermatitidis, Paracoccidioides brasiliensis, and Histoplasma capsulatum, have never been considered nosocomial pathogens, there are some factors that point out the pros and cons for this possibility. Among these fungi, H. capsulatum infection has been linked to different medical devices and surgery implants. The filamentous form of H. capsulatum may be present in hospital settings, as this fungus adapts to different types of climates and has great dispersion ability. Although conventional pathogen identification techniques have never identified H. capsulatum in the hospital environment, molecular biology procedures could be useful in this setting. More research on H. capsulatum as a HAI etiologic agent is needed, since it causes a severe and often fatal disease in immunocompromised patients.
Zafar Iqbal*, Uzma Sheikh and Rabia Mughal
Full Text Available Aim of this study was to investigate fungal infections in four species of carps including goldfish, Carassius (C. auratus L.; silver carp, Hypophthalmichthys (H. molitrix Richardsons; rahu, Labeo (L. rohita Hamilton and Ctenopharyngodon (C. idella Valenciennes. Nine specimens of each species were studied for the presence of fungal infections. Infected fishes showed clinical signs such as fungal growth on skin, fins, eyes, eroded fins and scales, hemorrhages on body surface and abdominal distension. The specimens from infected organs of fish were inoculated on each, malt extract, Sabouraud dextrose and potato dextrose agars. The fungal colonies of white, black, green, grey and brown colors were observed in the agar plates. Slides were prepared and stained with 0.05% Trypan blue in lactophenol. C. auratus showed the highest infection rate (44.4% followed by H. molitrix and L. rohita (11.1% each. Five fungal species viz. Aspergillus (33.3%, Penicillium (22.2%, Alternaria (27.7%, Blastomyces spp (11.1% and Rhizopus (5.5% were isolated. Posterior part of the fish had significantly (P=0.05 higher (62.5% infection as compared to anterior part (37.5%. The caudal fin with 31.25% infection was the single most affected area. This study showed that most of the fungi isolated from fishes are considered as normal mycoflora, yet many fungi can cause natural infections in ponds and aquarium.
Pamela P. Lee
Full Text Available The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV, hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs. Dimorphic fungi such as Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis, Sporothrix schenckii, Talaromyces (Penicillium marneffei, and Emmonsia spp. are geographically restricted to their respective habitats and cause endemic mycoses. Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are recognized as acquired immunodeficiency syndrome (AIDS-defining conditions, while the rest also cause high rate of morbidities and mortalities in patients with HIV infection and other immunocompromised conditions. In the past decade, a growing number of monogenic immunodeficiency disorders causing increased susceptibility to fungal infections have been discovered. In particular, defects of the IL-12/IFN-γ pathway and T-helper 17-mediated response are associated with increased susceptibility to endemic mycoses. In this review, we put together the various forms of endemic mycoses on the map and take a journey around the world to examine how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections, including primary immunodeficiencies, individuals with autoantibodies against interferon-γ, and those receiving biologic response modifiers. Though rare, these conditions provide importance insights to host defense mechanisms against endemic fungi, which can only be appreciated in unique
Zhu, D; Wang, J; Zeng, Q; Zhang, Z; Yan, R
To characterize and identify a novel Huperzine A (HupA)-producing fungal strain Slf14 isolated from Huperzia serrata (Thunb. ex Murray) Trev. in China. The isolation, identification and characterization of a novel endophytic fungus producing HupA specifically and consistently from the leaves of H. serrata were investigated. The fungus was identified as Shiraia sp. Slf14 by molecular and morphological methods. The HupA produced by this endophytic fungus was shown to be identical to authentic HupA analysed by thin layer chromatographic, High-performance liquid chromatography (HPLC), LC-MS, (1) H NMR and acetylcholinesterase (AChE) inhibition activity in vitro. The amount of HupA produced by Shiraia sp. Slf14 was quantified to be 327.8 μg l(-1) by HPLC, which was far higher than that of the reported endophytic fungi, Acremonium sp., Blastomyces sp. and Botrytis sp. The production of HupA by endophyte Shiraia sp. Slf14 is an enigmatic observation. It would be interesting to further study the HupA production and regulation by the cultured endophyte in H. serrata and in axenic cultures. Although the current accumulation of HupA by the endophyte is not very high, it could provide a promising alterative approach for large-scale production of HupA. However, further strain improvement and the fermentation process optimization are required to result in the consistent and dependable production. © 2010 The Authors. Journal compilation © 2010 The Society for Applied Microbiology.
Full Text Available Twenty-three cases of blastomycosis were reported in a survey conducted in the province of Quebec from 1981–90. Thirteen patients resided south of the St Lawrence River and the other 10, north. Two small geographical clusters were apparent in and around the cities of Sherbrooke and Quebec. The male to female ratio was 1.6:1 and the median age was 47 years (range 26 to 77. Lung involvement was observed in 19 cases and was the only site involved in 11. Cutaneous manifestations were reported in 11 cases while bone infection (three cases and central nervous system (CNS infections were also noted. Diagnosis was confirmed by culture in 21 cases and by histopathology in two cases. Of the 21 culture-positive cases, 12 strains of Blastomyces dermatitidis were isolated from lungs, nine from skin, and one each from bone and brain. Serodiagnostic tests by immunodiffusion or complement fixation were positive for only one of the 10 patients known to have been tested. Ten patients were treated with amphotericin B, 11 with ketoconazole, one with fluconazole and eight underwent surgery. While amphotericin B was used in eight of the 10 earliest treated cases, ketoconazole was administered in 10 of the 13 more recent cases. Of the patients for whom follow-up data have been obtained, 21 are reported cured (one of whom was not treated and one patient died of another cause. This survey confirms that blastomycosis is a rare disease in this endemic area and that patterns of therapy are changing.
Martins Natalia F
Full Text Available Abstract Background The prevalence of invasive fungal infections (IFIs has increased steadily worldwide in the last few decades. Particularly, there has been a global rise in the number of infections among immunosuppressed people. These patients present severe clinical forms of the infections, which are commonly fatal, and they are more susceptible to opportunistic fungal infections than non-immunocompromised people. IFIs have historically been associated with high morbidity and mortality, partly because of the limitations of available antifungal therapies, including side effects, toxicities, drug interactions and antifungal resistance. Thus, the search for alternative therapies and/or the development of more specific drugs is a challenge that needs to be met. Genomics has created new ways of examining genes, which open new strategies for drug development and control of human diseases. Results In silico analyses and manual mining selected initially 57 potential drug targets, based on 55 genes experimentally confirmed as essential for Candida albicans or Aspergillus fumigatus and other 2 genes (kre2 and erg6 relevant for fungal survival within the host. Orthologs for those 57 potential targets were also identified in eight human fungal pathogens (C. albicans, A. fumigatus, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Paracoccidioides lutzii, Coccidioides immitis, Cryptococcus neoformans and Histoplasma capsulatum. Of those, 10 genes were present in all pathogenic fungi analyzed and absent in the human genome. We focused on four candidates: trr1 that encodes for thioredoxin reductase, rim8 that encodes for a protein involved in the proteolytic activation of a transcriptional factor in response to alkaline pH, kre2 that encodes for α-1,2-mannosyltransferase and erg6 that encodes for Δ(24-sterol C-methyltransferase. Conclusions Our data show that the comparative genomics analysis of eight fungal pathogens enabled the identification of
Dennis J. Baumgardner
Full Text Available Purpose: Blastomycosis is a serious fungal infection contracted by inhalation of Blastomyces spores from the environment. Case occurrence in dogs in Vilas County, Wisconsin, has been associated with antecedent weather. We aimed to explore the effects of weather on the occurrence of human pulmonary blastomycosis in this area, and update exposure factors and symptoms since last published reports. Methods: Mandatory case reports were reviewed. Chi-square test was used for categorical data of exposures, comparing 1979–1996 (n=101 versus 1997–June 2013 (n=95. Linear regression was used to model local weather data (available 1990–2013; n=126; Southern Oscillation Index (SOI, North Atlantic Oscillation Index (NAOI, and Wisconsin River water discharge (WRD from the adjacent county (all available for 1984–2013; n=174; and case counts of known onset by warm (April–September and cold (October–March 6-month periods. Results: Distribution of pulmonary blastomycosis cases did not vary by season. Environmental exposures for the 1997–June 2013 group (mean age 45, 59% male were: residence(76%, excavation (42% and gardening (31%, all similar to the 1979–1996 group. Fishing (23% vs. 37%; P=0.09 and hunting (15% vs. 26%; P=0.13 exposures were less common in 1997–June 2013, but not significantly different. Overall, 69% of cases recalled some prior soil-disturbing activities. Considering the 6-month warm/cold periods, 19% of variation is explained by a direct relationship with total precipitation from two periods prior (P=0.005. There was no association of case occurrence with SOI, NAOI or WRD. Estimated annual incidence of blastomycosis for 1997–June 2013 was 27/100,000 compared with 44/100,000 for 1984–1996. Several symptoms were significantly less frequent in 2002–June 2013 compared to earlier years. Conclusions: As with dogs, human pulmonary blastomycosis occurrence is partially determined by antecedent precipitation. It is unclear if