NANNAN LIU; QIANG XU; FANG ZHU; LEE ZHANG
Repeated blood feedings throughout their life span have made mosquitoes ideal transmitters of a wide variety of disease agents. Vector control is a very important part of the current global strategy for the control of mosquito-associated diseases and insecticide application is the most important component in this effort. Pyrethroids, which account for 25% of the world insecticide market, are currently the most widely used insecticides for the indoor control of mosquitoes and are the only chemical recommended for the treatment of mosquito nets, the main tool for preventing malaria in Africa. However, mosquito-borne diseases are now resurgent, largely because of insecticide resistance that has developed in mosquito vectors and the anti-parasite drug resistance of parasites. This paper reviews our current knowledge of the molecular mechanisms governing metabolic detoxification and the development of target site insensitivity that leads to pyrethroid resistance in mosquitoes.
Horn fly resistance to pyrethroid insecticides occurs throughout Brazil, but knowledge about the involved mechanisms is still in an incipient stage. This survey was aimed to identify the mechanisms of horn fly resistance to cypermethrin in Mato Grosso do Sul state, Brazil. Impregnated filter paper bioassays using cypermethrin, synergized or not with piperonyl butoxide (PBO) and triphenyl phosphate (TPP), were conducted from March 2004 to June 2005 in horn fly populations (n = 33) from all ove...
Adelman, Zach N; Kilcullen, Kathleen A; Koganemaru, Reina; Anderson, Michelle A E; Anderson, Troy D; Miller, Dini M
A frightening resurgence of bed bug infestations has occurred over the last 10 years in the U.S. and current chemical methods have been inadequate for controlling this pest due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in U.S. bed bug populations, making it extremely difficult to develop intelligent strategies for their control. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I) and metabolic resistance to pyrethroid insecticides. Using LD(50) bioassays, we determined that resistance ratios for Richmond strain bed bugs were ∼5200-fold to the insecticide deltamethrin. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible) and Richmond (resistant) bed bugs revealed several candidate cytochrome P450 and carboxylesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance.
Zach N Adelman
Full Text Available A frightening resurgence of bed bug infestations has occurred over the last 10 years in the U.S. and current chemical methods have been inadequate for controlling this pest due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in U.S. bed bug populations, making it extremely difficult to develop intelligent strategies for their control. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I and metabolic resistance to pyrethroid insecticides. Using LD(50 bioassays, we determined that resistance ratios for Richmond strain bed bugs were ∼5200-fold to the insecticide deltamethrin. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible and Richmond (resistant bed bugs revealed several candidate cytochrome P450 and carboxylesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance.
Antonio Thadeu Medeiros Barros
Full Text Available Horn fly resistance to pyrethroid insecticides occurs throughout Brazil, but knowledge about the involved mechanisms is still in an incipient stage. This survey was aimed to identify the mechanisms of horn fly resistance to cypermethrin in Mato Grosso do Sul state, Brazil. Impregnated filter paper bioassays using cypermethrin, synergized or not with piperonyl butoxide (PBO and triphenyl phosphate (TPP, were conducted from March 2004 to June 2005 in horn fly populations (n = 33 from all over the state. All populations were highly resistant to cypermethrin, with resistance factors (RF ranging from 89.4 to 1,020.6. Polymerase chain reaction (PCR assays to detect the knockdown resistance (kdr mutation also were performed in 16 samples. The kdr mutation was found in 75% of the tested populations, mostly with relatively low frequencies (<20%, and was absent in some highly resistant populations. Addition of TPP did not significantly reduce the LC50 in any population. However, PBO reduced LC50s above 40-fold in all tested populations, resulting in RFs ≤ 10 in most cases. Horn fly resistance to cypermethrin is widespread in the state, being primarily caused by an enhanced activity of P450 mono-oxygenases and secondarily by reduced target site sensitivity.
Carvalho, Renato A; Omoto, Celso; Field, Linda M; Williamson, Martin S; Bass, Chris
The fall armyworm Spodoptera frugiperda is an economically important pest of small grain crops that occurs in all maize growing regions of the Americas. The intensive use of chemical pesticides for its control has led to the selection of resistant populations, however, to date, the molecular mechanisms underlying resistance have not been characterised. In this study the mechanisms involved in the resistance of two S. frugiperda strains collected in Brazil to chlorpyrifos (OP strain) or lambda-cyhalothrin (PYR strain) were investigated using molecular and genomic approaches. To examine the possible role of target-site insensitivity the genes encoding the organophosphate (acetylcholinesterase, AChE) and pyrethroid (voltage-gated sodium channel, VGSC) target-site proteins were PCR amplified. Sequencing of the S. frugiperda ace-1 gene identified several nucleotide changes in the OP strain when compared to a susceptible reference strain (SUS). These result in three amino acid substitutions, A201S, G227A and F290V, that have all been shown previously to confer organophosphate resistance in several other insect species. Sequencing of the gene encoding the VGSC in the PYR strain, identified mutations that result in three amino acid substitutions, T929I, L932F and L1014F, all of which have been shown previously to confer knockdown/super knockdown-type resistance in several arthropod species. To investigate the possible role of metabolic detoxification in the resistant phenotype of the OP and PYR stains all EST sequences available for S. frugiperda were used to design a gene-expression microarray. This was then used to compare gene expression in the resistant strains with the susceptible reference strain. Members of several gene families, previously implicated in metabolic resistance in other insects were found to be overexpressed in the resistant strains including glutathione S-transferases, cytochrome P450s and carboxylesterases. Taken together these results provide
Renato A Carvalho
Full Text Available The fall armyworm Spodoptera frugiperda is an economically important pest of small grain crops that occurs in all maize growing regions of the Americas. The intensive use of chemical pesticides for its control has led to the selection of resistant populations, however, to date, the molecular mechanisms underlying resistance have not been characterised. In this study the mechanisms involved in the resistance of two S. frugiperda strains collected in Brazil to chlorpyrifos (OP strain or lambda-cyhalothrin (PYR strain were investigated using molecular and genomic approaches. To examine the possible role of target-site insensitivity the genes encoding the organophosphate (acetylcholinesterase, AChE and pyrethroid (voltage-gated sodium channel, VGSC target-site proteins were PCR amplified. Sequencing of the S. frugiperda ace-1 gene identified several nucleotide changes in the OP strain when compared to a susceptible reference strain (SUS. These result in three amino acid substitutions, A201S, G227A and F290V, that have all been shown previously to confer organophosphate resistance in several other insect species. Sequencing of the gene encoding the VGSC in the PYR strain, identified mutations that result in three amino acid substitutions, T929I, L932F and L1014F, all of which have been shown previously to confer knockdown/super knockdown-type resistance in several arthropod species. To investigate the possible role of metabolic detoxification in the resistant phenotype of the OP and PYR stains all EST sequences available for S. frugiperda were used to design a gene-expression microarray. This was then used to compare gene expression in the resistant strains with the susceptible reference strain. Members of several gene families, previously implicated in metabolic resistance in other insects were found to be overexpressed in the resistant strains including glutathione S-transferases, cytochrome P450s and carboxylesterases. Taken together these results
Full Text Available BACKGROUND: Establishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for resistance management. Here, we report a widespread distribution of insecticide resistance in the major malaria vector An. funestus across Uganda and western Kenya under the control of metabolic resistance mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: Female An. funestus collected throughout Uganda and western Kenya exhibited a Plasmodium infection rate between 4.2 to 10.4%. Widespread resistance against both type I (permethrin and II (deltamethrin pyrethroids and DDT was observed across Uganda and western Kenya. All populations remain highly susceptible to carbamate, organophosphate and dieldrin insecticides. Knockdown resistance plays no role in the pyrethroid and DDT resistance as no kdr mutation associated with resistance was detected despite the presence of a F1021C replacement. Additionally, no signature of selection was observed on the sodium channel gene. Synergist assays and qRT-PCR indicated that metabolic resistance plays a major role notably through elevated expression of cytochrome P450s. DDT resistance mechanisms differ from West Africa as the L119F-GSTe2 mutation only explains a small proportion of the genetic variance to DDT resistance. CONCLUSION: The extensive distribution of pyrethroid and DDT resistance in East African An. funestus populations represents a challenge to the control of this vector. However, the observed carbamate and organophosphate susceptibility offers alternative solutions for resistance management.
Eiden, A L; Kaufman, P E; Oi, F M; Dark, M J; Bloomquist, J R; Miller, R J
Rhipicephalus sanguineus (Latreille) (Ixodida: Ixodidae) is a three-host dog tick found worldwide that is able to complete its' entire lifecycle indoors. Options for the management of R. sanguineus are limited and its' control relies largely on only a few acaricidal active ingredients. Previous studies have confirmed permethrin resistance and fipronil tolerance in R. sanguineus populations, commonly conferred by metabolic detoxification or target site mutations. Herein, five strains of permethrin-resistant and three strains of fipronil-tolerant ticks were evaluated for metabolic resistance using synergists to block metabolic enzymes. Synergist studies were completed with triphenyl phosphate (TPP) for esterase inhibition, piperonyl butoxide (PBO) for cytochrome P450 inhibition, and diethyl maleate (DEM) for glutathione-S-transferase inhibition. Additionally, increased esterase activity was confirmed using gel electrophoresis. The most important metabolic detoxification mechanism in permethrin-resistant ticks was increased esterase activity, followed by increased cytochrome P450 activity. The inhibition of metabolic enzymes did not have a marked impact on fipronil-tolerant tick strains. © 2017 The Royal Entomological Society.
Dorte H Højland
Full Text Available Cabbage stem flea beetle (CSFB, Psylliodes chrysocephala L. (Coleoptera: Chrysomelidae is a major early season pest of oilseed rape throughout Europe. Pyrethroids have been used for controlling this pest by foliar application, but in recent years control failures have occurred, particularly in Germany due to the evolution of knock-down resistance (kdr. The purpose of this study was to investigate the incidence and spread of pyrethroid resistance in CSFB collected in Germany, Denmark and the United Kingdom during 2014. The level of pyrethroid resistance was measured in adult vial tests and linked to the presence of kdr genotypes.Although kdr (L1014F genotypes are present in all three countries, marked differences in pyrethroid efficacy were found in adult vial tests. Whereas Danish CSFB samples were in general susceptible to recommended label rates, those collected in the UK mostly resist such rates to some extent. Moderately resistant and susceptible samples were found in Germany. Interestingly, some of the resistant samples from the UK did not carry the kdr allele, which is in contrast to German CSFB. Pre-treatment with PBO, prior to exposure to λ-cyhalothrin suggested involvement of metabolic resistance in UK samples.Danish samples were mostly susceptible with very low resistance ratios, while most other samples showed reduced sensitivity in varying degrees. Likewise, there was a clear difference in the presence of the kdr mutation between the three countries. In the UK, the presence of kdr genotypes did not always correlate well with resistant phenotypes. This appears to be primarily conferred by a yet undisclosed, metabolic-based mechanism. Nevertheless our survey disclosed an alarming trend concerning the incidence and spread of CSFB resistance to pyrethroids, which is likely to have negative impacts on oilseed production in affected regions due to the lack of alternative modes of action for resistance management purposes.
Full Text Available Aedes aegypti is the major vector of yellow and dengue fevers. After 10 generations of adult selection, an A. aegypti strain (SP developed 1650-fold resistance to permethrin, which is one of the most widely used pyrethroid insecticides for mosquito control. SP larvae also developed 8790-fold resistance following selection of the adults. Prior to the selections, the frequencies of V1016G and F1534C mutations in domains II and III, respectively, of voltage-sensitive sodium channel (Vssc, the target site of pyrethroid insecticide were 0.44 and 0.56, respectively. In contrast, only G1016 alleles were present after two permethrin selections, indicating that G1016 can more contribute to the insensitivity of Vssc than C1534. In vivo metabolism studies showed that the SP strain excreted permethrin metabolites more rapidly than a susceptible SMK strain. Pretreatment with piperonyl butoxide caused strong inhibition of excretion of permethrin metabolites, suggesting that cytochrome P450 monooxygenases (P450s play an important role in resistance development. In vitro metabolism studies also indicated an association of P450s with resistance. Microarray analysis showed that multiple P450 genes were over expressed during the larval and adult stages in the SP strain. Following quantitative real time PCR, we focused on two P450 isoforms, CYP9M6 and CYP6BB2. Transcription levels of these P450s were well correlated with the rate of permethrin excretion and they were certainly capable of detoxifying permethrin to 4'-HO-permethrin. Over expression of CYP9M6 was partially due to gene amplification. There was no significant difference in the rate of permethrin reduction from cuticle between SP and SMK strains.
Full Text Available Pyrethroid insecticides are widely used to control insect pests and human disease vectors. Voltage-gated sodium channels are the primary targets of pyrethroid insecticides. Mutations in the sodium channel have been shown to be responsible for pyrethroid resistance, known as knockdown resistance (kdr, in various insects including mosquitoes. In Aedes aegypti mosquitoes, the principal urban vectors of dengue, zika, and yellow fever viruses, multiple single nucleotide polymorphisms in the sodium channel gene have been found in pyrethroid-resistant populations and some of them have been functionally confirmed to be responsible for kdr in an in vitro expression system, Xenopus oocytes. This mini-review aims to provide an update on the identification and functional characterization of pyrethroid resistance-associated sodium channel mutations from Aedes aegypti. The collection of kdr mutations not only helped us develop molecular markers for resistance monitoring, but also provided valuable information for computational molecular modeling of pyrethroid receptor sites on the sodium channel.
Du, Yuzhe; Nomura, Yoshiko; Zhorov, Boris S.; Dong, Ke
Pyrethroid insecticides are widely used to control insect pests and human disease vectors. Voltage-gated sodium channels are the primary targets of pyrethroid insecticides. Mutations in the sodium channel have been shown to be responsible for pyrethroid resistance, known as knockdown resistance (kdr), in various insects including mosquitoes. In Aedes aegypti mosquitoes, the principal urban vectors of dengue, zika, and yellow fever viruses, multiple single nucleotide polymorphisms in the sodium channel gene have been found in pyrethroid-resistant populations and some of them have been functionally confirmed to be responsible for kdr in an in vitro expression system, Xenopus oocytes. This mini-review aims to provide an update on the identification and functional characterization of pyrethroid resistance-associated sodium channel mutations from Aedes aegypti. The collection of kdr mutations not only helped us develop molecular markers for resistance monitoring, but also provided valuable information for computational molecular modeling of pyrethroid receptor sites on the sodium channel. PMID:27809228
Shi, Linna; Hu, Hongxia; Ma, Kai; Zhou, Dan; Yu, Jing; Zhong, Daibin; Fang, Fujin; Chang, Xuelian; Hu, Shengli; Zou, Feifei; Wang, Weijie; Sun, Yan; Shen, Bo; Zhang, Donghui; Ma, Lei; Zhou, Guofa; Yan, Guiyun; Zhu, Changliang
Current vector control programs are largely dependent on pyrethroids, which are the most commonly used and only insecticides recommended by the World Health Organization for insecticide-treated nets (ITNs). However, the rapid spread of pyrethroid resistance worldwide compromises the effectiveness of control programs and threatens public health. Since few new insecticide classes for vector control are anticipated, limiting the development of resistance is crucial for prolonging efficacy of pyrethroids. In this study, we exposed a field-collected population of Culex pipiens pallens to different insecticide selection intensities to dynamically monitor the development of resistance. Moreover, we detected kdr mutations and three detoxification enzyme activities in order to explore the evolutionary mechanism of pyrethroid resistance. Our results revealed that the level of pyrethroid resistance was proportional to the insecticide selection pressure. The kdr and metabolic resistance both contributed to pyrethroid resistance in the Cx. pipiens pallens populations, but they had different roles under different selection pressures. We have provided important evidence for better understanding of the development and mechanisms of pyrethroid resistance which may guide future insecticide use and vector management in order to avoid or delay resistance.
Full Text Available Current vector control programs are largely dependent on pyrethroids, which are the most commonly used and only insecticides recommended by the World Health Organization for insecticide-treated nets (ITNs. However, the rapid spread of pyrethroid resistance worldwide compromises the effectiveness of control programs and threatens public health. Since few new insecticide classes for vector control are anticipated, limiting the development of resistance is crucial for prolonging efficacy of pyrethroids. In this study, we exposed a field-collected population of Culex pipiens pallens to different insecticide selection intensities to dynamically monitor the development of resistance. Moreover, we detected kdr mutations and three detoxification enzyme activities in order to explore the evolutionary mechanism of pyrethroid resistance. Our results revealed that the level of pyrethroid resistance was proportional to the insecticide selection pressure. The kdr and metabolic resistance both contributed to pyrethroid resistance in the Cx. pipiens pallens populations, but they had different roles under different selection pressures. We have provided important evidence for better understanding of the development and mechanisms of pyrethroid resistance which may guide future insecticide use and vector management in order to avoid or delay resistance.
陈澄宇; 史雪岩; 髙希武
随着拟除虫菊酯类杀虫剂在卫生和农业害虫防治中的广泛应用，昆虫对此类杀虫剂产生抗性的报道越来越多。目前已明确昆虫对拟除虫菊酯类杀虫剂的抗性机制包括表皮穿透率下降、靶标抗性以及代谢抗性，其中代谢抗性机制较为普遍，而且其与昆虫对多种杀虫剂的交互抗性关系密切。目前，随着基因组、转录组以及蛋白质组学等新技术的发展及应用，昆虫对拟除虫菊酯类杀虫剂的代谢抗性机制研究也取得了很多新进展。昆虫体内细胞色素 P450酶(P450s)、羧酸酯酶(CarE)及谷胱甘肽S-转移酶(GSTs)等重要解毒酶系的改变均与昆虫对拟除虫菊酯类杀虫剂的代谢抗性有关，其中这3类解毒酶的活性及相关基因表达量的变化是昆虫对此类杀虫剂产生代谢抗性的主要原因。明确昆虫对拟除虫菊酯类杀虫剂的代谢抗性机制，对合理使用此类杀虫剂及延缓抗药性的产生均具有重要意义。本文在总结拟除虫菊酯类杀虫剂代谢路径及相关生物酶研究概况的基础上，综述了近年来有关昆虫对此类杀虫剂代谢抗性机制研究的主要进展。%With indiscriminate use of pyrethroid insecticides on agricultural and urban settings insect pests, the pyrethroid resistance in insects has occurred widely. The resistance mechanisms of insects to pyrethroid insecticides include the resistance caused by the decline of insect cuticular penetration rate, insensitive target resistance and metabolic resistance. Among those mechanisms, the metabolic resistance of insects to pyrethroids is more commonly existed and closely related to insects cross resistance to a variety of insecticides. Recently, many new achievements on the mechanisms of insect metabolic resistance to pyrethroids insecticides have been obtained, with the application of new techniques such as proteomics, transcriptome and genomic techniques. The changes of
Smith, Letícia B; Kasai, Shinji; Scott, Jeffrey G
Aedes aegypti and A. albopictus mosquitoes are vectors of important human disease viruses, including dengue, yellow fever, chikungunya and Zika. Pyrethroid insecticides are widely used to control adult Aedes mosquitoes, especially during disease outbreaks. Herein, we review the status of pyrethroid resistance in A. aegypti and A. albopictus, mechanisms of resistance, fitness costs associated with resistance alleles and provide suggestions for future research. The widespread use of pyrethroids has given rise to many populations with varying levels of resistance worldwide, albeit with substantial geographical variation. In adult A. aegypti and A. albopictus, resistance levels are generally lower in Asia, Africa and the USA, and higher in Latin America, although there are exceptions. Susceptible populations still exist in several areas of the world, particularly in Asia and South America. Resistance to pyrethroids in larvae is also geographically widespread. The two major mechanisms of pyrethroid resistance are increased detoxification due to P450-monooxygenases, and mutations in the voltage sensitive sodium channel (Vssc) gene. Several P450s have been putatively associated with insecticide resistance, but the specific P450s involved are not fully elucidated. Pyrethroid resistance can be due to single mutations or combinations of mutations in Vssc. The presence of multiple Vssc mutations can lead to extremely high levels of resistance. Suggestions for future research needs are presented. Copyright © 2016 Elsevier B.V. All rights reserved.
Dong, Ke; Du, Yuzhe; Rinkevich, Frank; Nomura, Yoshiko; Xu, Peng; Wang, Lingxin; Silver, Kristopher; Zhorov, Boris S
Voltage-gated sodium channels are essential for the initiation and propagation of the action potential in neurons and other excitable cells. Because of their critical roles in electrical signaling, sodium channels are targets of a variety of naturally occurring and synthetic neurotoxins, including several classes of insecticides. This review is intended to provide an update on the molecular biology of insect sodium channels and the molecular mechanism of pyrethroid resistance. Although mammalian and insect sodium channels share fundamental topological and functional properties, most insect species carry only one sodium channel gene, compared to multiple sodium channel genes found in each mammalian species. Recent studies showed that two posttranscriptional mechanisms, alternative splicing and RNA editing, are involved in generating functional diversity of sodium channels in insects. More than 50 sodium channel mutations have been identified to be responsible for or associated with knockdown resistance (kdr) to pyrethroids in various arthropod pests and disease vectors. Elucidation of molecular mechanism of kdr led to the identification of dual receptor sites of pyrethroids on insect sodium channels. Many of the kdr mutations appear to be located within or close to the two receptor sites. The accumulating knowledge of insect sodium channels and their interactions with insecticides provides a foundation for understanding the neurophysiology of sodium channels in vivo and the development of new and safer insecticides for effective control of arthropod pests and human disease vectors.
Dong, Ke; Du, Yuzhe; Rinkevich, Frank; Nomura, Yoshiko; Xu, Peng; Wang, Lingxin; Silver, Kristopher; Zhorov, Boris S.
Voltage-gated sodium channels are essential for the initiation and propagation of the action potential in neurons and other excitable cells. Because of their critical roles in electrical signaling, sodium channels are targets of a variety of naturally occurring and synthetic neurotoxins, including several classes of insecticides. This review is intended to provide an update on the molecular biology of insect sodium channels and the molecular mechanism of pyrethroid resistance. Although mammalian and insect sodium channels share fundamental topological and functional properties, most insect species carry only one sodium channel gene, compared to multiple sodium channel genes found in each mammalian species. Recent studies showed that two posttranscriptional mechanisms, alternative splicing and RNA editing, are involved in generating functional diversity of sodium channels in insects. More than 50 sodium channel mutations have been identified to be responsible for or associated with knockdown resistance (kdr) to pyrethroids in various arthropod pests and disease vectors. Elucidation of molecular mechanism of kdr led to the identification of dual receptor sites of pyrethroids on insect sodium channels. Most of the kdr mutations appear to be located within or close to the two receptor sites. The accumulating knowledge of insect sodium channels and their interactions with insecticides provides a foundation for understanding the neurophysiology of sodium channels in vivo and the development of new and safer insecticides for effective control of arthropod pests and human disease vectors. PMID:24704279
Wei, Y; Appel, A G; Moar, W J; Liu, N
A German cockroach (Blatella germanica (L)) strain, Apyr-R, was collected from Opelika, Alabama after control failures with pyrethroid insecticides. Levels of resistance to permethrin and deltamethrin in Apyr-R (97- and 480-fold, respectively, compared with a susceptible strain, ACY) were partially or mostly suppressed by piperonyl butoxide (PBO) and S,S,S,-tributylphosphorotrithioate (DEF), suggesting that P450 monooxygenases and hydrolases are involved in resistance to these two pyrethroids in Apyr-R. However, incomplete suppression of pyrethroid resistance with PBO and DEF implies that one or more additional mechanisms are involved in resistance. Injection, compared with topical application, resulted in 43- and 48-fold increases in toxicity of permethrin in ACY and Apyr-R, respectively. Similarly, injection increased the toxicity of deltamethrin 27-fold in ACY and 28-fold in Apyr-R. These data indicate that cuticular penetration is one of the obstacles for the effectiveness of pyrethroids against German cockroaches. However, injection did not change the levels of resistance to either permethrin or deltamethrin, suggesting that a decrease in the rate of cuticular penetration may not play an important role in pyrethroid resistance in Apyr-R. Apyr-R showed cross-resistance to imidacloprid, with a resistance ratio of 10. PBO treatment resulted in no significant change in the toxicity of imidacloprid, implying that P450 monooxygenase-mediated detoxication is not the mechanism responsible for cross-resistance. Apyr-R showed no cross-resistance to spinosad, although spinosad had relatively low toxicity to German cockroaches compared with other insecticides tested in this study. This result further confirmed that the mode of action of spinosad to insects is unique. Fipronil, a relatively new insecticide, was highly toxic to German cockroaches, and the multi-resistance mechanisms in Apyr-R did not confer significant cross-resistance to this compound. Thus, we propose
Muthusamy, R; Shivakumar, M S
Pesticide resistance poses a serious problem for worldwide mosquito control programs. Resistance to insecticides can be caused by an increased metabolic detoxification of the insecticide and/or by target site insensitivity. In the present study, we estimated the tolerance of Indian Aedes aegypti populations using adult bioassays that revealed high resistance levels of the field populations to permethrin (RR-6, 5.8 and 5.1 folds) compared to our susceptible population. Enzymatic assays revealed increased activities of glutathione S-transferase and carboxylesterase enzymes in the field populations comparatively to the susceptible population. PBO synergist assays did not confirm that cytochrome P450 monooxygenase metabolic detoxification acted as a major cause of resistance. Hence the role of target site resistance was therefore investigated. A single substitution Phe1534Cys in the voltage gated sodium channel was found in domain III, segment 6 (III-S6) of the resistance populations (allele frequency=0.59, 0.51 and 0.47) suggesting its potential role in permethrin resistance in A. aegypti.
Zhu, Fang; Gujar, Hemant; Gordon, Jennifer R; Haynes, Kenneth F; Potter, Michael F; Palli, Subba R
Recent advances in genomic and post-genomic technologies have facilitated a genome-wide analysis of the insecticide resistance-associated genes in insects. Through bed bug, Cimex lectularius transcriptome analysis, we identified 14 molecular markers associated with pyrethroid resistance. Our studies revealed that most of the resistance-associated genes functioning in diverse mechanisms are expressed in the epidermal layer of the integument, which could prevent or slow down the toxin from reaching the target sites on nerve cells, where an additional layer of resistance (kdr) is possible. This strategy evolved in bed bugs is based on their unique morphological, physiological and behavioral characteristics and has not been reported in any other insect species. RNA interference-aided knockdown of resistance associated genes showed the relative contribution of each mechanism towards overall resistance development. Understanding the complexity of adaptive strategies employed by bed bugs will help in designing the most effective and sustainable bed bug control methods.
Full Text Available Abstract Background Malaria in South Africa is primarily transmitted by Anopheles funestus Giles. Resistance to pyrethroid insecticides in An. funestus in northern Kwazulu/Natal, South Africa, and in neighbouring areas of southern Mozambique enabled populations of this species to increase their ranges into areas where pyrethroids were being exclusively used for malaria control. Pyrethroid resistance in southern African An. funestus is primarily conferred by monooxygenase enzyme metabolism. However, selection for this resistance mechanism is likely to have occurred in conjunction with other factors that improve production of the resistance phenotype. A strong candidate is cuticle thickening. This is because thicker cuticles lead to slower rates of insecticide absorption, which is likely to increase the efficiency of metabolic detoxification. Results Measures of mean cuticle thickness in laboratory samples of female An. funestus were obtained using scanning electron microscopy (SEM. These females were drawn from a laboratory colony carrying the pyrethroid resistance phenotype at a stable rate, but not fixed. Prior to cuticle thickness measurements, these samples were characterised as either more or less tolerant to permethrin exposure in one experiment, and either permethrin resistant or susceptible in another experiment. There was a significant and positive correlation between mean cuticle thickness and time to knock down during exposure to permethrin. Mean cuticle thickness was significantly greater in those samples characterised either as more tolerant or resistant to permethrin exposure compared to those characterised as either less tolerant or permethrin susceptible. Further, insecticide susceptible female An. funestus have thicker cuticles than their male counterparts. Conclusion Pyrethroid tolerant or resistant An. funestus females are likely to have thicker cuticles than less tolerant or susceptible females, and females generally have
John C Morgan
Full Text Available BACKGROUND: The susceptibility status of Anopheles funestus to insecticides remains largely unknown in most parts of Africa because of the difficulty in rearing field-caught mosquitoes of this malaria vector. Here we report the susceptibility status of the An. funestus population from Tororo district in Uganda and a preliminary characterisation of the putative resistance mechanisms involved. METHODOLOGY/PRINCIPAL FINDINGS: A new forced egg laying technique used in this study significantly increased the numbers of field-caught females laying eggs and generated more than 4000 F1 adults. WHO bioassays indicated that An. funestus in Tororo is resistant to pyrethroids (62% mortality after 1 h exposure to 0.75% permethrin and 28% mortality to 0.05% deltamethrin. Suspected DDT resistance was also observed with 82% mortality. However this population is fully susceptible to bendiocarb (carbamate, malathion (organophosphate and dieldrin with 100% mortality observed after exposure to each of these insecticides. Sequencing of a fragment of the sodium channel gene containing the 1014 codon conferring pyrethroid/DDT resistance in An. gambiae did not detect the L1014F kdr mutation but a correlation between haplotypes and resistance phenotype was observed indicating that mutations in other exons may be conferring the knockdown resistance in this species. Biochemical assays suggest that resistance in this population is mediated by metabolic resistance with elevated level of GSTs, P450s and pNPA compared to a susceptible strain of Anopheles gambiae. RT-PCR further confirmed the involvement of P450s with a 12-fold over-expression of CYP6P9b in the Tororo population compared to the fully susceptible laboratory colony FANG. CONCLUSION: This study represents the first report of pyrethroid/DDT resistance in An. funestus from East Africa. With resistance already reported in southern and West Africa, this indicates that resistance in An. funestus may be more widespread
Lilly, David G; Latham, Sharissa L; Webb, Cameron E; Doggett, Stephen L
Thickening of the integument as a mechanism of resistance to insecticides is a well recognised phenomenon in the insect world and, in recent times, has been found in insects exhibiting pyrethroid-resistance. Resistance to pyrethroid insecticides in the common bed bug, Cimex lectularius L., is widespread and has been frequently inferred as a reason for the pest's resurgence. Overexpression of cuticle depositing proteins has been demonstrated in pyrethroid-resistant bed bugs although, to date, no morphological analysis of the cuticle has been undertaken in order to confirm a phenotypic link. This paper describes examination of the cuticle thickness of a highly pyrethroid-resistant field strain collected in Sydney, Australia, in response to time-to-knockdown upon forced exposure to a pyrethroid insecticide. Mean cuticle thickness was positively correlated to time-to-knockdown, with significant differences observed between bugs knocked-down at 2 hours, 4 hours, and those still unaffected at 24 hours. Further analysis also demonstrated that the 24 hours survivors possessed a statistically significantly thicker cuticle when compared to a pyrethroid-susceptible strain of C. lectularius. This study demonstrates that cuticle thickening is present within a pyrethroid-resistant strain of C. lectularius and that, even within a stable resistant strain, cuticle thickness will vary according to time-to-knockdown upon exposure to an insecticide. This response should thus be considered in future studies on the cuticle of insecticide-resistant bed bugs and, potentially, other insects.
Oxborough, Richard M; Kitau, Jovin; Matowo, Johnson; Feston, Emmanuel; Mndeme, Rajab; Mosha, Franklin W; Rowland, Mark W
Pyrethroid resistant Anopheles gambiae malaria vectors are widespread throughout sub-Saharan Africa and continued efficacy of pyrethroid ITNs is under threat. Chlorfenapyr is a promising pyrrole insecticide with a unique mechanism of action conferring no cross-resistance to existing public health insecticides. Mixtures of chlorfenapyr (CFP) and alphacypermethrin (alpha) may provide additional benefits over chlorfenapyr or alphacypermethrin used alone. An ITN mixture of CFP 100 mg/m(2)+alpha 25 mg/m(2) was compared with CFP 100 mg/m(2) and alpha 25 mg/m(2) in a small-scale experimental hut trial in an area of wild An. arabiensis. The same treatments were evaluated in tunnel tests against insectary-reared pyrethroid susceptible and resistant Culex quinquefasciatus. Performance was measured in terms of insecticide-induced mortality, and blood-feeding inhibition. Tunnel tests showed that mixtures of CFP 100+ alpha 25 were 1.2 and 1.5 times more effective at killing susceptible Cx. quinquefasciatus than either Alpha 25 (P = 0.001) or CFP 100 (P = 0.001) ITNs. Mixtures of CFP100+ alpha 25 were 2.2 and 1.2 times more effective against resistant Cx. quinquefasciatus than either alpha 25 (P = 0.001) or CFP100 (P = 0.003) ITNs. CFP 100+ alpha 25 produced higher levels of blood-feeding inhibition than CFP alone for susceptible (94 vs 46%, P = 0.001) and resistant (84 vs 53%, P = 0.001) strains. In experimental huts the mixture of CFP 100+ Alpha 25 killed 58% of An. arabiensis, compared with 50% for alpha and 49% for CFP, though the differences were not significant. Blood-feeding inhibition was highest in the mixture with a 76% reduction compared to the untreated net (P = 0.001). ITN mixtures of chlorfenapyr and alphacypermethrin should restore effective control of resistant populations of An. gambiae malaria vectors, provide protection from blood-feeding, and may have benefits for resistance management, particularly in areas with low or moderate
Richard M Oxborough
Full Text Available Pyrethroid resistant Anopheles gambiae malaria vectors are widespread throughout sub-Saharan Africa and continued efficacy of pyrethroid ITNs is under threat. Chlorfenapyr is a promising pyrrole insecticide with a unique mechanism of action conferring no cross-resistance to existing public health insecticides. Mixtures of chlorfenapyr (CFP and alphacypermethrin (alpha may provide additional benefits over chlorfenapyr or alphacypermethrin used alone. An ITN mixture of CFP 100 mg/m(2+alpha 25 mg/m(2 was compared with CFP 100 mg/m(2 and alpha 25 mg/m(2 in a small-scale experimental hut trial in an area of wild An. arabiensis. The same treatments were evaluated in tunnel tests against insectary-reared pyrethroid susceptible and resistant Culex quinquefasciatus. Performance was measured in terms of insecticide-induced mortality, and blood-feeding inhibition. Tunnel tests showed that mixtures of CFP 100+ alpha 25 were 1.2 and 1.5 times more effective at killing susceptible Cx. quinquefasciatus than either Alpha 25 (P = 0.001 or CFP 100 (P = 0.001 ITNs. Mixtures of CFP100+ alpha 25 were 2.2 and 1.2 times more effective against resistant Cx. quinquefasciatus than either alpha 25 (P = 0.001 or CFP100 (P = 0.003 ITNs. CFP 100+ alpha 25 produced higher levels of blood-feeding inhibition than CFP alone for susceptible (94 vs 46%, P = 0.001 and resistant (84 vs 53%, P = 0.001 strains. In experimental huts the mixture of CFP 100+ Alpha 25 killed 58% of An. arabiensis, compared with 50% for alpha and 49% for CFP, though the differences were not significant. Blood-feeding inhibition was highest in the mixture with a 76% reduction compared to the untreated net (P = 0.001. ITN mixtures of chlorfenapyr and alphacypermethrin should restore effective control of resistant populations of An. gambiae malaria vectors, provide protection from blood-feeding, and may have benefits for resistance management, particularly in areas with low or
Romero, Alvaro; Potter, Michael F; Haynes, Kenneth F
An understanding of the mechanisms of insecticide resistance in the bed bug, Cimex lectularius L., has the potential to lead to new approaches for the control of resistant populations. We used the cytochrome P450 monooxygenase (P450) inhibitor piperonyl butoxide (PBO) to assess the role of P450s in deltamethrin resistance in three field-collected bed bug strains, LA-1, CIN-1 and WOR-1. In addition, we exposed two highly resistant strains, CIN-1 and WOR-1 (resistance ratio [RR] >2,500-fold), to dry residues of piperonyl butoxide-synergized pyrethroid formulations to determine the utility of synergism by PBO. Piperonyl butoxide synergized deltamethrin in all three strains, but its impact was variable. The synergistic ratio varied from 40 in CIN-1 to 176 in WOR-1. Because the resistance ratio for each strain after piperonyl butoxide treatment was 174 and 39, respectively, our results suggest that P450s have some involvement in deltamethrin resistance, but other resistance mechanisms must be involved as well. No significant synergistic effect of formulated deltamethrin was observed with the addition of synergized pyrethrins or formulated piperonyl butoxide in the CIN-1 strain, but synergism occurred in the WOR-1 strain. Addition of PBO to pyrethroids is not a comprehensive solution to pyrethroid resistance because strains vary in both overall resistance level and the proportion of that resistance attributable to P450s.
Full Text Available The Varroa mite, Varroa destructor, is an important pest of honeybees and has played a prominent role in the decline in bee colony numbers over recent years. Although pyrethroids such as tau-fluvalinate and flumethrin can be highly effective in removing the mites from hives, their intensive use has led to many reports of resistance. To investigate the mechanism of resistance in UK Varroa samples, the transmembrane domain regions of the V. destructor voltage-gated sodium channel (the main target site for pyrethroids were PCR amplified and sequenced from pyrethroid treated/untreated mites collected at several locations in Central/Southern England. A novel amino acid substitution, L925V, was identified that maps to a known hot spot for resistance within the domain IIS5 helix of the channel protein; a region that has also been proposed to form part of the pyrethroid binding site. Using a high throughput diagnostic assay capable of detecting the mutation in individual mites, the L925V substitution was found to correlate well with resistance, being present in all mites that had survived tau-fluvalinate treatment but in only 8 % of control, untreated samples. The potential for using this assay to detect and manage resistance in Varroa-infected hives is discussed.
González-Cabrera, Joel; Davies, T G Emyr; Field, Linda M; Kennedy, Peter J; Williamson, Martin S
The Varroa mite, Varroa destructor, is an important pest of honeybees and has played a prominent role in the decline in bee colony numbers over recent years. Although pyrethroids such as tau-fluvalinate and flumethrin can be highly effective in removing the mites from hives, their intensive use has led to many reports of resistance. To investigate the mechanism of resistance in UK Varroa samples, the transmembrane domain regions of the V. destructor voltage-gated sodium channel (the main target site for pyrethroids) were PCR amplified and sequenced from pyrethroid treated/untreated mites collected at several locations in Central/Southern England. A novel amino acid substitution, L925V, was identified that maps to a known hot spot for resistance within the domain IIS5 helix of the channel protein; a region that has also been proposed to form part of the pyrethroid binding site. Using a high throughput diagnostic assay capable of detecting the mutation in individual mites, the L925V substitution was found to correlate well with resistance, being present in all mites that had survived tau-fluvalinate treatment but in only 8 % of control, untreated samples. The potential for using this assay to detect and manage resistance in Varroa-infected hives is discussed.
Full Text Available BACKGROUND: Although Anopheles funestus is difficult to rear, it is crucial to analyse field populations of this malaria vector in order to successfully characterise mechanisms of insecticide resistance observed in this species in Africa. In this study we carried out a large-scale field collection and rearing of An. funestus from Mozambique in order to analyse its susceptibility status to insecticides and to broadly characterise the main resistance mechanisms involved in natural populations. METHODOLOGY/PRINCIPAL FINDINGS: 3,000 F(1 adults were obtained through larval rearing. WHO susceptibility assays indicated a very high resistance to pyrethroids with no mortality recorded after 1 h 30 min exposure and less than 50% mortality at 3 h 30 min. Resistance to the carbamate, bendiocarb was also noted, with 70% mortality after 1h exposure. In contrast, no DDT resistance was observed, indicating that no kdr-type resistance was involved. The sequencing of the acetylcholinesterase gene indicated the absence of the G119S and F455W mutations associated with carbamate and organophosphate resistance. This could explain the absence of malathion resistance in this population. Both biochemical assays and quantitative PCR implicated up-regulated P450 genes in pyrethroid resistance, with GSTs playing a secondary role. The carbamate resistance observed in this population is probably conferred by the observed altered AChE with esterases also involved. CONCLUSION/SIGNIFICANCE: The high level of pyrethroid resistance in this population despite the cessation of pyrethroid use for IRS in 1999 is a serious concern for resistance management strategies such as rotational use of insecticides. As DDT has now been re-introduced for IRS, susceptibility to DDT needs to be closely monitored to prevent the appearance and spread of resistance to this insecticide.
Donnelly Martin J
Full Text Available Abstract Background Mosquito resistance to the pyrethroid insecticides used to treat bednets threatens the sustainability of malaria control in sub-Saharan Africa. While the impact of target site insensitivity alleles is being widely discussed the implications of insecticide detoxification – though equally important – remains elusive. The successful development of new tools for malaria intervention and management requires a comprehensive understanding of insecticide resistance, including metabolic resistance mechanisms. Although three enzyme families (cytochrome P450s, glutathione S-transferases and carboxylesterases have been widely associated with insecticide detoxification the role of individual enzymes is largely unknown. Results Here, constitutive expression patterns of genes putatively involved in conferring pyrethroid resistance was investigated in a recently colonised pyrethroid resistant Anopheles gambiae strain from Odumasy, Southern Ghana. RNA from the resistant strain and a standard laboratory susceptible strain, of both sexes was extracted, reverse transcribed and labelled with either Cy3- or Cy5-dye. Labelled cDNA was co-hybridised to the detox chip, a custom-made microarray containing over 230 A. gambiae gene fragments predominantly from enzyme families associated with insecticide resistance. After hybridisation, Cy3- and Cy5-signal intensities were measured and compared gene by gene. In both females and males of the resistant strain the cytochrome P450s CYP6Z2 and CYP6M2 are highly over-expressed along with a member of the superoxide dismutase (SOD gene family. Conclusion These genes differ from those found up-regulated in East African strains of pyrethroid resistant A. gambiae and constitute a novel set of candidate genes implicated in insecticide detoxification. These data suggest that metabolic resistance may have multiple origins in A. gambiae, which has strong implications for the management of resistance.
Mechanisms of pyrethroid resistance in Haematobia irritans (Muscidae from Mato Grosso do Sul state, Brazil Mecanismos de resistência da Haematobia irritans (Muscidae a piretróides em Mato Grosso do Sul, Brasil
Antonio Thadeu Medeiros Barros
Full Text Available Horn fly resistance to pyrethroid insecticides occurs throughout Brazil, but knowledge about the involved mechanisms is still in an incipient stage. This survey was aimed to identify the mechanisms of horn fly resistance to cypermethrin in Mato Grosso do Sul state, Brazil. Impregnated filter paper bioassays using cypermethrin, synergized or not with piperonyl butoxide (PBO and triphenyl phosphate (TPP, were conducted from March 2004 to June 2005 in horn fly populations (n = 33 from all over the state. All populations were highly resistant to cypermethrin, with resistance factors (RF ranging from 89.4 to 1,020.6. Polymerase chain reaction (PCR assays to detect the knockdown resistance (kdr mutation also were performed in 16 samples. The kdr mutation was found in 75% of the tested populations, mostly with relatively low frequencies (Resistência da mosca-dos-chifres a inseticidas piretróides ocorre em todo o país, entretanto, o conhecimento sobre os mecanismos envolvidos é ainda incipiente. Este estudo objetivou identificar os mecanismos de resistência desta mosca à cipermetrina em Mato Grosso do Sul. Bioensaios utilizando papéis impregnados com cipermetrina, isoladamente ou sinergizada por butóxido de piperonila (PBO ou trifenil fosfato (TPP, foram realizados de março∕2004 a junho∕2005 em 33 populações. Todas as populações apresentaram elevada resistência à cipermetrina, com fatores de resistência (FR variando de 89,4 a 1.020,6. Ensaios de reação em cadeia da polimerase (PCR visando a detecção de kdr (“knockdown resistance” foram realizados em 16 amostras. A mutação kdr foi detectada em 75% das populações, geralmente em baixas frequências (<20% e ausente em algumas populações resistentes. A adição de TPP não reduziu significativamente a CL50 em nenhuma população. Entretanto, o PBO reduziu em mais de 40 vezes a CL50 de todas as populações testadas, resultando em FR ≤ 10 na maioria dos casos. Resist
Wanjala, Christine L; Mbugi, Jernard P; Ototo, Edna; Gesuge, Maxwell; Afrane, Yaw A; Atieli, Harrysone E; Zhou, Guofa; Githeko, Andrew K; Yan, Guiyun
We conducted standard insecticide susceptibility testing across western Kenya and found that the Anopheles gambiae mosquito has acquired high resistance to pyrethroids and DDT, patchy resistance to carbamates, but no resistance to organophosphates. Use of non-pyrethroid-based vector control tools may be preferable for malaria prevention in this region.
Pyrethroid resistance is a serious problem to cattle producers in Brazil. There are specific resistance-associated mutations, known as kdr and super-kdr, in the region of DNA that codes for the target of pyrethroids, the sodium channel protein. The presence of these mutations in the sodium channel c...
Nauen, Ralf; Zimmer, Christoph T; Andrews, Melanie
by cytochrome P450 monooxygenases was implicated in the resistance of several pollen beetle populations from different European regions. Here, we have also investigated the possible occurrence of a target-site mechanism caused by modification of the pollen beetle para-type voltage-gated sodium channel gene. We....... No super-kdr mutations (e.g. M918T) known to cause resistance to pyrethroids were detected. The implications of these results for resistance management strategies of pollen beetle populations in oilseed rape crops are discussed....
N'Guessan, R; Boko, P; Odjo, A; Akogbéto, M; Yates, A; Rowland, M
Owing to the development and spread of pyrethroid resistance in Anopheles gambiae in Africa there is an urgent need to develop alternative insecticides to supplement the pyrethroids. Chlorfenapyr is a pyrrole insecticide first commercialized for the control of agricultural pests and termites. Performance against An. gambiae bearing kdr (pyrethroid and DDT resistance) or Ace-1(R) insensitive acetylcholinesterase (organophosphate and carbamate resistance) mechanisms was studied using a variety of adult bioassay tests including a simulated-experimental hut system (tunnel tests) that allows uninhibited mosquito behaviour/insecticide interactions. Strains resistant to pyrethroids and organophosphates showed no cross resistance to chlorfenapyr. In cone bioassays on treated netting the mortality of adult mosquitoes showed an unexpected curvilinear response, with highest mortality occurring at intermediate dosages. Adults expressed irritability to chlorfenapyr at higher dosages, which might explain the dosage-mortality trend. Toxic activity of chlorfenapyr was slow compared to conventional neurotoxic insecticides and additional mortality occurred between 24h and 72 h. In tunnel tests, the dosage-mortality trend showed a more typical sigmoid response and most mortality occurred during the first 24h. Mosquito penetration through the holed, treated netting showed only limited inhibition and blood-feeding was not inhibited. Mortality rates in the kdr strain exposed to chlorfenapyr treated netting in tunnel tests were much higher than with permethrin treated netting over the same 100-500 mg/m(2) dosage range. Chlorfenapyr has potential for malaria control in treated-net or residual spraying applications in areas where mosquitoes are pyrethroid resistant. For treated-net applications chlorfenapyr might be combined with pyrethroid as a mixture to provide personal protection as well as to give control of resistant mosquitoes.
In response to selection pressure from pesticides, Anopheles mosquitoes have evolved resistance to those pesticides. These mosquitoes have different mechanisms of resistance to different types of pesticides since those pesticides have different mechanisms of action. This paper summarizes recent advances in the study of factors such as esterases, P45O monooxygenases, glutathione S-transferases, and insensitive sodium channels that may relate to resistance to pyrethroids in Anopheles mosquitoes,%在杀虫剂的选择压力下蚊虫形成抗药性,不同类型的杀虫剂,由于其作用机制不同,其抗性分子机制也会有所不同.本文对按蚊拟除虫菊酯类杀虫剂抗药性相关因素酯酶、细胞色素P450单加氧酶、谷胱甘肽S-转移酶及神经轴突钠离子通道等的研究进展进行了综述.
Full Text Available Abstract Background Pyrethroid resistance is now widespread in Anopheles gambiae, the major vector for malaria in sub-Saharan Africa. This resistance may compromise malaria vector control strategies that are currently in use in endemic areas. In this context, a new tool for management of resistant mosquitoes based on the combination of a pyrethroid-treated bed net and carbamate-treated plastic sheeting was developed. Methods In the laboratory, the insecticidal activity and wash resistance of four carbamate-treated materials: a cotton/polyester blend, a polyvinyl chloride tarpaulin, a cotton/polyester blend covered on one side with polyurethane, and a mesh of polypropylene fibres was tested. These materials were treated with bendiocarb at 100 mg/m2 and 200 mg/m2 with and without a binding resin to find the best combination for field studies. Secondly, experimental hut trials were performed in southern Benin to test the efficacy of the combined use of a pyrethroid-treated bed net and the carbamate-treated material that was the most wash-resistant against wild populations of pyrethroid-resistant An. gambiae and Culex quinquefasciatus. Results Material made of polypropylene mesh (PPW provided the best wash resistance (up to 10 washes, regardless of the insecticide dose, the type of washing, or the presence or absence of the binding resin. The experimental hut trial showed that the combination of carbamate-treated PPW and a pyrethroid-treated bed net was extremely effective in terms of mortality and inhibition of blood feeding of pyrethroid-resistant An. gambiae. This efficacy was found to be proportional to the total surface of the walls. This combination showed a moderate effect against wild populations of Cx. quinquefasciatus, which were strongly resistant to pyrethroid. Conclusion These preliminary results should be confirmed, including evaluation of entomological, parasitological, and clinical parameters. Selective pressure on resistance
Al Nazawi, Ashwaq M; Aqili, Jabir; Alzahrani, Mohammed; McCall, Philip J; Weetman, David
Pyrethroid resistance is a threat to effective vector control of Aedes aegypti, the vector of dengue, Zika and other arboviruses, but there are many major knowledge gaps on the mechanisms of resistance. In Jeddah and Makkah, the principal dengue-endemic areas of Saudi Arabia, pyrethroids are used widely for Ae. aegypti control but information about resistance remains sparse, and the underlying genetic basis is unknown. Findings from an ongoing study in this internationally significant area are reported here. Aedes aegypti collected from each city were raised to adults and assayed for resistance to permethrin, deltamethrin (with and without the synergist piperonyl butoxide, PBO), fenitrothion, and bendiocarb. Two fragments of the voltage-gated sodium channel (Vgsc), encompassing four previously identified mutation sites, were sequenced and subsequently genotyped to determine associations with resistance. Expression of five candidate genes (CYP9J10, CYP9J28, CYP9J32, CYP9M6, ABCB4) previously associated with pyrethroid resistance was compared between assay survivors and controls. Jeddah and Makkah populations exhibited resistance to multiple insecticides and a similarly high prevalence of resistance to deltamethrin compared to a resistant Cayman strain, with a significant influence of age and exposure duration on survival. PBO pre-exposure increased pyrethroid mortality significantly in the Jeddah, but not the Makkah strain. Three potentially interacting Vgsc mutations were detected: V1016G and S989P were in perfect linkage disequilibrium in each strain and strongly predicted survival, especially in the Makkah strain, but were in negative linkage disequilibrium with 1534C, though some females with the Vgsc triple mutation were detected. The candidate gene CYP9J28 was significantly over-expressed in Jeddah compared to two susceptible reference strains, but none of the candidate genes was consistently up-regulated to a significant level in the Makkah strain. Despite
Suzuki, Yusuke; Ishizaka, Shoji; Kitamura, Noboru
A novel radical trapping technique combined with a fluorescence spectroscopic analysis has been employed to investigate the radical intermediates produced by photodecarboxylation of four synthetic pyrethroids: fenvalerate (SMD), fenpropathrin (DTL), cyphenothrin (GKL), and cypermethrin (AGT). Under photoirradiation at >290 nm, all pyrethroids underwent direct photolysis via homolytic cleavage of the carbon-oxygen bonds in the ester groups. The consumed amount of a nitroxide free radical, as a trapping agent for the intermediate radical of a pyrethroid, was determined by ESR, which was the measure of the reaction yield of a photochemically generated α-cyano-3-phenoxybenzyl radical common to all pyrethroids. The reactivities of the pyrethroids studied was in the sequence of SMD > DTL > GKL > AGT. Furthermore, nanosecond transient absorption spectroscopy demonstrated that geminate recombination of the radical pair within a solvent cage is the main deactivation route of the photochemically generated α-cyano-3-phenoxybenzyl radical common for all pyrethroids studied.
Lilly, David G; Webb, Cameron E; Doggett, Stephen L
Insecticide resistance in bed bugs (Cimex lectularius and Cimex hemipterus) has become widespread, which has necessitated the development of new IPM (Integrated Pest Management) strategies and products for the eradication of infestations. Two promising options are the diatomaceous earth and silica gel-based desiccant dusts, both of which induce dehydration and eventual death upon bed bugs exposed to these products. However, the impact of underlying mechanisms that confer resistance to insecticides, such as cuticle thickening, on the performance of these dusts has yet to be determined. In the present study, two desiccant dusts, CimeXa Insecticide Dust (silica gel) and Bed Bug Killer Powder (diatomaceous earth) were evaluated against two strains of C. lectularius; one highly pyrethroid-resistant and one insecticide-susceptible. Label-rate doses of both products produced 100% mortality in both strains, albeit over dissimilar time-frames (3-4 days with CimeXa vs. 14 days with Bed Bug Killer). Sub-label rate exposure to CimeXa indicated that the pyrethroid-resistant strain possessed a degree of tolerance to this product, surviving 50% longer than the susceptible strain. This is the first study to suggest that mechanisms conferring resistance to pyrethroids, such as cuticular thickening, may have potential secondary impacts on non-synthetic insecticides, including desiccant dusts, which target the bed bug's cuticle.
David G. Lilly
Full Text Available Insecticide resistance in bed bugs (Cimex lectularius and Cimex hemipterus has become widespread, which has necessitated the development of new IPM (Integrated Pest Management strategies and products for the eradication of infestations. Two promising options are the diatomaceous earth and silica gel-based desiccant dusts, both of which induce dehydration and eventual death upon bed bugs exposed to these products. However, the impact of underlying mechanisms that confer resistance to insecticides, such as cuticle thickening, on the performance of these dusts has yet to be determined. In the present study, two desiccant dusts, CimeXa Insecticide Dust (silica gel and Bed Bug Killer Powder (diatomaceous earth were evaluated against two strains of C. lectularius; one highly pyrethroid-resistant and one insecticide-susceptible. Label-rate doses of both products produced 100% mortality in both strains, albeit over dissimilar time-frames (3–4 days with CimeXa vs. 14 days with Bed Bug Killer. Sub-label rate exposure to CimeXa indicated that the pyrethroid-resistant strain possessed a degree of tolerance to this product, surviving 50% longer than the susceptible strain. This is the first study to suggest that mechanisms conferring resistance to pyrethroids, such as cuticular thickening, may have potential secondary impacts on non-synthetic insecticides, including desiccant dusts, which target the bed bug’s cuticle.
Fountain, Toby; Ravinet, Mark; Naylor, Richard; Reinhardt, Klaus; Butlin, Roger K
The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species. Copyright © 2016 Fountain et al.
Full Text Available The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG, with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species.
Fountain, Toby; Ravinet, Mark; Naylor, Richard; Reinhardt, Klaus; Butlin, Roger K.
The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species. PMID:27733453
Full Text Available BACKGROUND: Pyrethroid insecticides are widely utilized in dengue control. However, the major vector, Aedes aegypti, is becoming increasingly resistant to these insecticides and this is impacting on the efficacy of control measures. The near complete transcriptome of two pyrethroid resistant populations from the Caribbean was examined to explore the molecular basis of this resistance. PRINCIPAL FINDINGS: Two previously described target site mutations, 1016I and 1534C were detected in pyrethroid resistant populations from Grand Cayman and Cuba. In addition between two and five per cent of the Ae. aegypti transcriptome was differentially expressed in the resistant populations compared to a laboratory susceptible population. Approximately 20 per cent of the genes over-expressed in resistant mosquitoes were up-regulated in both Caribbean populations (107 genes. Genes with putative monooxygenase activity were significantly over represented in the up-regulated subset, including five CYP9 P450 genes. Quantitative PCR was used to confirm the higher transcript levels of multiple cytochrome P450 genes from the CYP9J family and an ATP binding cassette transporter. Over expression of two genes, CYP9J26 and ABCB4, is due, at least in part, to gene amplification. SIGNIFICANCE: These results, and those from other studies, strongly suggest that increases in the amount of the CYP9J cytochrome P450s are an important mechanism of pyrethroid resistance in Ae. aegypti. The genetic redundancy resulting from the expansion of this gene family makes it unlikely that a single gene or mutation responsible for pyrethroid resistance will be identified in this mosquito species. However, the results from this study do pave the way for the development of new pyrethroid synergists and improved resistance diagnostics. The role of copy number polymorphisms in detoxification and transporter genes in providing protection against insecticide exposure requires further investigation.
Full Text Available Bed bugs are hematophagous insects responsible for a re-emerging and challenging indoor pest in many countries. Bed bugs infestations may have health consequences including nuisance biting, cutaneous and systemic reactions. This resurgence can probably be attributed to factors such as increased international travel and development of resistance against insecticides. Resistance against pyrethroids has been reported several times from the USA and rarely in Europe. In France, very few data on bed bugs are available. The present study aimed to assess the infestation by bed bugs of a complex of two high-rise apartment buildings in the suburb of Paris and to evaluate their susceptibility to pyrethroid insecticides. We inspected for bed bugs 192 out of 198 apartments units (97% and interviewed their residents. 76 (39.6% apartments were infested. Among the 97 residents living in infested apartments, 53 (54.6% reported bed bug bites. A total of 564 bed bugs were collected in the infested units. Bioassays showed that 54 out of 143 bed bugs were resistant to pyrethroids (37.8%; 95% confidence interval: 29.9-45.7%. DNA sequencing showed that all bed bugs tested (n = 124 had homozygous L925I kdr-like gene mutation. The level of pyrethroid resistance found indicates that this phenomenon was already established in the site and prompts the need to reevaluate the wide use of pyrethroids to control bed bugs.
Durand, R; Cannet, A; Berdjane, Z; Bruel, C; Haouchine, D; Delaunay, P; Izri, A
Bed bugs are hematophagous insects responsible for a re-emerging and challenging indoor pest in many countries. Bed bugs infestations may have health consequences including nuisance biting, cutaneous and systemic reactions. This resurgence can probably be attributed to factors such as increased international travel and development of resistance against insecticides. Resistance against pyrethroids has been reported several times from the USA and rarely in Europe. In France, very few data on bed bugs are available. The present study aimed to assess the infestation by bed bugs of a complex of two high-rise apartment buildings in the suburb of Paris and to evaluate their susceptibility to pyrethroid insecticides. We inspected for bed bugs 192 out of 198 apartments units (97%) and interviewed their residents. 76 (39.6%) apartments were infested. Among the 97 residents living in infested apartments, 53 (54.6%) reported bed bug bites. A total of 564 bed bugs were collected in the infested units. Bioassays showed that 54 out of 143 bed bugs were resistant to pyrethroids (37.8%; 95% confidence interval: 29.9-45.7%). DNA sequencing showed that all bed bugs tested (n=124) had homozygous L925I kdr-like gene mutation. The level of pyrethroid resistance found indicates that this phenomenon was already established in the site and prompts the need to reevaluate the wide use of pyrethroids to control bed bugs.
N'Guessan, Raphael; Boko, Pelagie; Odjo, Abiba; Knols, Bart; Akogbeto, Martin; Rowland, Mark
To compare the efficacy of chlorfenapyr applied on mosquito nets and as an indoor residual spray against populations of Anopheles gambiae and Culex quinquefasciatus in an area of Benin that shows problematic levels of pyrethroid resistance. Eight-week trial conducted in experimental huts. Indoor residual spraying killed 82.9% of An. gambiae overall (mean mortality: 79.5%) compared to 53.5% overall (mean mortality: 61.7%) in the hut containing the lower dosed ITN. Analysis of data on a fortnightly basis showed high levels of mosquito mortality and blood-feeding inhibition during the first few weeks after treatment. Control of C. quinquefasciatus by the IRS and ITN interventions showed a similar trend to that of An. gambiae and though the average level of mortality was lower it was still much higher than with pyrethroid treatments against this population. Chlorfenapyr's reputation for being rather slow acting was evident particularly at lower dosages. The treatments showed no evidence of excito-repellent activity in this trial. Chlorfenapyr has the potential to control pyrethroid resistant populations of A. gambiae. There is a need to develop long-lasting formulations of chlorfenapyr to prolong its residual life on nets and sprayed surfaces. On nets it could be combined with a contact irritant pyrethroid to give improved protection against mosquito biting while killing pyrethroid-resistant mosquitoes that come into contact with the net.
Kasai, S; Sun, H; Scott, J G
Insecticide use exerts a tremendous selection force on house fly populations, but the frequencies of the initial resistance mutations may not reach high levels if they have a significant fitness cost in the absence of insecticides. However, with the continued use of the same (or similar) insecticides, it is expected that new mutations (conferring equal or greater resistance, but less of a fitness cost) will evolve. Pyrethroid insecticides target the insect voltage sensitive sodium channel (VSSC) and have been widely used for control of house flies at animal production facilities for more than three decades. There are three Vssc mutations known that cause resistance to pyrethroids in house flies: knockdown resistance (kdr, L1014F), kdr-his (L1014H) and super-kdr (M918T + L1014F). Whether or not there are any new mutations in house fly populations has not been examined for decades. We collected house flies from a dairy in Kansas (USA) and selected this population for three generations. We discovered multiple new Vssc alleles, including two that give very high levels of resistance to most pyrethroids. The importance of these findings to understanding the evolution of insecticide resistance, designing appropriate resistance monitoring and management schemes, and the future of pyrethroids for house fly control are discussed. © 2016 The Royal Entomological Society.
Guerrero, Felix D; Barros, A Thadeu M
The horn fly, Haematobia irritans irritans (L.) (Diptera: Muscidae), has become a problem for Brazilian cattle producers even though its introduction into Brazil is relatively recent. Failure to control this cattle pest is becoming a concern, and horn fly populations from several ranches from the state of Mato Grosso do Sul were surveyed for pyrethroid resistance. Susceptibility bioassays revealed that cypermethrin resistance was widespread and reached high levels in horn fly populations throughout the state, with resistance factors (RFs) ranging from 50.4 to 704.8. Synergist bioassays failed to detect a major role for esterases as a pyrethroid resistance mechanism in these populations, except for the highly pyrethroid-resistant Estrela do Oeste population (RF = 704.8). The kdr sodium channel gene mutation was not detected in eight of the 13 populations, but Oeste exhibited this mutation. Neither the superkdr sodium channel gene mutation nor a resistance-associated gene mutation in the HialphaE7 carboxylesterase were found in any of the fly populations. Although target site insensitivity (kdr) and esterase-mediated metabolism occur in horn fly populations from Mato Grosso do Sul state, it seems that they are not the major mechanism causing pyrethroid resistance in most of these populations.
Full Text Available Abstract Background In this study, the efficacy of insecticide-treated nets was evaluated in terms of deterrence, blood-feeding inhibition, induced exophily and mortality on a wild resistant population of Anopheles epiroticus in southern Vietnam, in order to gain insight into the operational consequences of the insecticide resistance observed in this malaria vector in the Mekong delta. Method An experimental station, based on the model of West Africa and adapted to the behaviour of the target species, was built in southern Vietnam. The study design was adapted from the WHO phase 2 guidelines. The study arms included a conventionally treated polyester net (CTN with deltamethrin washed just before exhaustion, the WHO recommended long-lasting insecticidal net (LLIN PermaNet 2.0® unwashed and 20 times washed and PermaNet 3.0®, designed for the control of pyrethroid resistant vectors, unwashed and 20 times washed. Results The nets still provided personal protection against the resistant An. epiroticus population. The personal protection ranged from 67% for deltamethrin CTN to 85% for unwashed PermaNet 3.0. Insecticide resistance in the An. epiroticus mosquitoes did not seem to alter the deterrent effect of pyrethroids. A significant higher mortality was still observed among the treatment arms despite the fact that the An. epiroticus population is resistant against the tested insecticides. Conclusion This study shows that CTN and LLINs still protect individuals against a pyrethroid resistant malaria vector from the Mekong region, where insecticide resistance is caused by a metabolic mechanism. In the light of a possible elimination of malaria from the Mekong region these insights in operational consequences of the insecticide resistance on control tools is of upmost importance.
Tangena, J.A.A.; Adiamoh, M.; Alessandro, D' U.; Jarju, L.; Jawara, M.; Jeffries, D.; Malik, N.; Nwakanma, D.; Kaur, H.; Takken, W.; Lindsay, S.W.; Pinder, M.
Background: Malaria vector control is threatened by resistance to pyrethroids, the only class of insecticides used for treating bed nets. The second major vector control method is indoor residual spraying with pyrethroids or the organochloride DDT. However, resistance to pyrethroids frequently confe
Ngufor, Corine; N'Guessan, Raphael; Boko, Pelagie; Odjo, Abibatou; Vigninou, Estelle; Asidi, Alex; Akogbeto, Martin; Rowland, Mark
.... Chlorfenapyr IRS and a pyrethroid-impregnated polyester LLIN (WHO approved) were tested separately and together in experimental huts in southern Benin against pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus...
Full Text Available Abstract Background Anopheles gambiae, the main malaria vector in Benin has developed high level of resistance to pyrethroid insecticides, which is a serious concern to the future use of long-lasting insecticidal nets (LLIN and indoor residual spraying (IRS. In this context, one of the pathways available for malaria vector control would be to investigate alternative classes of insecticides with different mode of action than that of pyrethroids. The goal of this study was to evaluate under field conditions the efficacy of a carbamate (bendiocarb and an organophosphate (fenitrothion against pyrethroid-resistant An. gambiae s.s. Methods Wild populations and females from laboratory colonies of five days old An. gambiae were bio-assayed during this study. Two pyrethroids (deltamethrin and alphacypermethrin, an organophosphate (fenitrothion, a carbamate (bendiocarb and a mixture of an organophosphate (chlorpyriphos + a pyrethroid deltamethrin were compared in experimental huts as IRS treatments. Insecticides were applied in the huts using a hand-operated compression sprayer. The deterrency, exophily, blood feeding rate and mortality induced by these insecticides against An. gambiae were compared to the untreated control huts. Results Deltamethrin, alphacypermethrin and bendiocarb treatment significantly reduced mosquito entry into the huts (p An. gambiae (in the first month and 77.8% (in the fourth month. Bendiocarb and the mixture chlorpyriphos/deltamethrin mortality rates ranged from 97.9 to 100% the first month and 77.7-88% the third month respectively. Conclusion After four months, fenitrothion, bendiocarb and the mixture chlorpyriphos/deltamethrin performed effectively against pyrethroid-resistant Anopheles. These results showed that bendiocarb could be recommended as an effective insecticide for use in IRS operations in Benin, particularly as the mixture chlorpyriphos/deltamethrin does not have WHOPES authorization and complaints were mentioned
N'Guessan, R.; Boko, P.; Odjo, A.; Knols, B.G.J.; Akogbeto, M.; Rowland, M.
Objective To compare the efficacy of chlorfenapyr applied on mosquito nets and as an indoor residual spray against populations of Anopheles gambiae and Culex quinquefasciatus in an area of Benin that shows problematic levels of pyrethroid resistance. Method Eight-week trial conducted in experimental
N'Guessan, R.; Boko, P.; Odjo, A.; Knols, B.G.J.; Akogbeto, M.; Rowland, M.
Objective To compare the efficacy of chlorfenapyr applied on mosquito nets and as an indoor residual spray against populations of Anopheles gambiae and Culex quinquefasciatus in an area of Benin that shows problematic levels of pyrethroid resistance. Method Eight-week trial conducted in experimental
Full Text Available Mosquito strains that exhibit increased tolerance to the chemical class of compounds with a sodium channel modulator mode of action (pyrethroids and pyrethrins are typically described as "pyrethroid resistant". Resistance to pyrethroids is an increasingly important challenge in the control of mosquito-borne diseases, such as malaria or dengue, because one of the main interventions (the distribution of large numbers of long-lasting insecticide-treated bed nets currently relies entirely on long-lasting pyrethroids. Increasing tolerance of target insects against this class of insecticides lowers their impact in vector control. The current study suggests that the level of metabolic resistance depends on the structure of the molecule and that structurally different compounds may still be effective because detoxifying enzymes are unable to bind to these uncommon structures.Treated surface contact bioassays were performed on susceptible Aedes aegypti, East African knockdown resistance (kdr Anopheles gambiae (strain RSP-H and metabolically resistant Anopheles funestus (strain FUMOZ-R with different pyrethroids, such as cypermethrin, ß-cyfluthrin, deltamethrin, permethrin and transfluthrin (alone and in combination with the synergist piperonyl butoxide. The nonfluorinated form of transfluthrin was also assessed as a single agent and in combination with piperonyl butoxide.Although the dosages for pyrethroids containing a phenoxybenzyl moiety have exhibited differences in terms of effectiveness among the three tested mosquito species, the structurally different transfluthrin with a polyfluorobenzyl moiety remained active in mosquitoes with upregulated P450 levels. In trials with transfluthrin mixed with piperonyl butoxide, the added synergist exhibited no efficacy-enhancing effect.The results of this study suggest that transfluthrin has the potential to control P450-mediated metabolically resistant mosquitoes because the structural formula of
Saavedra-Rodriguez, Karla; Beaty, Meaghan; Lozano-Fuentes, Saul; Denham, Steven; Garcia-Rejon, Julian; Reyes-Solis, Guadalupe; Machain-Williams, Carlos; Loroño-Pino, Maria Alba; Flores-Suarez, Adriana; Ponce-Garcia, Gustavo; Beaty, Barry; Eisen, Lars; Black, William C
The mosquito Aedes aegypti is the major vector of the four serotypes of dengue virus (DENV1-4). Previous studies have shown that Ae. aegypti in Mexico have a high effective migration rate and that gene flow occurs among populations that are up to 150 km apart. Since 2000, pyrethroids have been widely used for suppression of Ae. aegypti in cities in Mexico. In Yucatan State in particular, pyrethroids have been applied in and around dengue case households creating an opportunity for local selection and evolution of resistance. Herein, we test for evidence of local adaptation by comparing patterns of variation among 27 Ae. aegypti collections at 13 single nucleotide polymorphisms (SNPs): two in the voltage-gated sodium channel gene para known to confer knockdown resistance, three in detoxification genes previously associated with pyrethroid resistance, and eight in putatively neutral loci. The SNPs in para varied greatly in frequency among collections, whereas SNPs at the remaining 11 loci showed little variation supporting previous evidence for extensive local gene flow. Among Ae. aegypti in Yucatan State, Mexico, local adaptation to pyrethroids appears to offset the homogenizing effects of gene flow.
Saavedra-Rodriguez, Karla; Beaty, Meaghan; Lozano-Fuentes, Saul; Denham, Steven; Garcia-Rejon, Julian; Reyes-Solis, Guadalupe; Machain-Williams, Carlos; Loroño-Pino, Maria Alba; Flores-Suarez, Adriana; Ponce-Garcia, Gustavo; Beaty, Barry; Eisen, Lars; Black, William C.
The mosquito Aedes aegypti is the major vector of the four serotypes of dengue virus (DENV1–4). Previous studies have shown that Ae. aegypti in Mexico have a high effective migration rate and that gene flow occurs among populations that are up to 150 km apart. Since 2000, pyrethroids have been widely used for suppression of Ae. aegypti in cities in Mexico. In Yucatan State in particular, pyrethroids have been applied in and around dengue case households creating an opportunity for local selection and evolution of resistance. Herein, we test for evidence of local adaptation by comparing patterns of variation among 27 Ae. aegypti collections at 13 single nucleotide polymorphisms (SNPs): two in the voltage-gated sodium channel gene para known to confer knockdown resistance, three in detoxification genes previously associated with pyrethroid resistance, and eight in putatively neutral loci. The SNPs in para varied greatly in frequency among collections, whereas SNPs at the remaining 11 loci showed little variation supporting previous evidence for extensive local gene flow. Among Ae. aegypti in Yucatan State, Mexico, local adaptation to pyrethroids appears to offset the homogenizing effects of gene flow. PMID:25371186
Srivastava Harish C; Bhatt Rajendra M; Sharma Poonam; Barik Tapan K; Raghavendra Kamaraju; Sreehari Uragayala; Dash Aditya P
Abstract Background Malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. Hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. In the present study, chlorfenapyr was evaluated against Anopheles culicifacies and Anopheles stephensi for its possible use in vector control. Methods Efficacy of chlorfenapyr against An. culicifacies and An. ...
Oxborough, R M; Kitau, J; Matowo, J; Mndeme, R; Feston, E; Boko, P; Odjo, A; Metonnou, C G; Irish, S; N'guessan, R; Mosha, F W; Rowland, M W
Chlorfenapyr is a pyrrole insecticide with a unique non-neurological mode of action. Laboratory bioassays of chlorfenapyr comparing the mortality of pyrethroid-susceptible and -resistant Anopheles gambiae s.s. and Culex quinquefasciatus mosquitoes indicated that operational cross-resistance is unlikely to occur (resistance ratio ranged between 0 and 2.1). Three trials of chlorfenapyr indoor residual spraying were undertaken in experimental huts in an area of rice irrigation in northern Tanzania that supports breeding of A. arabiensis. Daily mosquito collections were undertaken to assess product performance primarily in terms of mortality. In the second trial, 250mg/m(2) and 500mg/m(2) chlorfenapyr were tested for residual efficacy over 6 months. Both dosages killed 54% of C. quinquefasciatus, whilst for A. arabiensis 250mg/m(2) killed 48% compared with 41% for 500mg/m(2); mortality was as high at the end of the trial as at the beginning. In the third trial, 250mg/m(2) chlorfenapyr was compared with the pyrethroid alpha-cypermethrin dosed at 30mg/m(2). Chlorfenapyr performance was equivalent to the pyrethroid against A. arabiensis, with both insecticides killing 50% of mosquitoes. Chlorfenapyr killed a significantly higher proportion of pyrethroid-resistant C. quinquefasciatus (56%) compared with alpha-cypermethrin (17%). Chlorfenapyr has the potential to be an important addition to the limited arsenal of public health insecticides for indoor residual control of A. arabiensis and pyrethroid-resistant species of mosquito. Copyright © 2010 Royal Society of Tropical Medicine and Hygiene.
Mosqueira, Beatriz; Soma, Dieudonné D; Namountougou, Moussa; Poda, Serge; Diabaté, Abdoulaye; Ali, Ouari; Fournet, Florence; Baldet, Thierry; Carnevale, Pierre; Dabiré, Roch K; Mas-Coma, Santiago
A pilot study to test the efficacy of combining an organophosphate-based insecticide paint and pyrethroid-treated Long Lasting Insecticide Treated Nets (LLINs) against pyrethroid-resistant malaria vector mosquitoes was performed in a real village setting in Burkina Faso. Paint Inesfly 5A IGR™, comprised of two organophosphates (OPs) and an Insect Growth Regulator (IGR), was tested in combination with pyrethroid-treated LLINs. Efficacy was assessed in terms of mortality for 12 months using Early Morning Collections of malaria vectors and 30-minute WHO bioassays. Resistance to pyrethroids and OPs was assessed by detecting the frequency of L1014F and L1014S kdr mutations and Ace-1(R)G119S mutation, respectively. Blood meal origin was identified using a direct enzyme-linked immunosorbent assay (ELISA). The combination of Inesfly 5A IGR™ and LLINs was effective in killing 99.9-100% of malaria vector populations for 6 months regardless of the dose and volume treated. After 12 months, mortality rates decreased to 69.5-82.2%. The highest mortality rates observed in houses treated with 2 layers of insecticide paint and a larger volume. WHO bioassays supported these results: mortalities were 98.8-100% for 6 months and decreased after 12 months to 81.7-97.0%. Mortality rates in control houses with LLINs were low. Collected malaria vectors consisted exclusively of Anopheles coluzzii and were resistant to pyrethroids, with a L1014 kdr mutation frequency ranging from 60 to 98% through the study. About 58% of An. coluzzii collected inside houses had bloodfed on non-human animals. Combining Inesfly 5A IGR™ and LLINs yielded a one year killing efficacy against An. coluzzii highly resistant to pyrethroids but susceptible to OPs that exhibited an anthropo-zoophilic behaviour in the study area. The results obtained in a real setting supported previous work performed in experimental huts and underscore the need to study the impact that this novel strategy may have on clinical
Full Text Available German cockroaches have become a large problem in the Shenzhen area because of their pesticide resistance, especially to pyrethroid. A pyrethroid called “Jia Chong Qing” to prevent pests for a long time were found to be resistant to “Jia Chong Qing” with resistance index of 3.88 measured using RT-PCR and immunohistochemistry analysis showed that both CYP4G19 mRNA and CYP4G19 protein expression levels in the wild strain were substantially higher than that of a sensitive strain. dsRNA segments derived from the target gene CYP4G19 were prepared using in vitro transcription and were microinjected into abdomens of the wild strain. Two to eight days after injection, the result showed that CYP4G19 mRNA expressions were significantly reduced in the groups injected with dsRNAs.
Oliver, S V; Kaiser, M L; Wood, O R; Coetzee, M; Rowland, M; Brooke, B D
To evaluate the pyrrole insecticide chlorfenapyr, which has a novel non-neurotoxic mode of action and is a promising alternative to conventional adulticides, against Anopheles funestus. The toxicity of a range of concentrations of chlorfenapyr against pyrethroid resistant and susceptible laboratory reared southern African An. funestus was assessed using standard WHO protocols and analysed using probit analysis. The pyrethroid resistant strain showed consistently higher LD50 and LD95 values compared to the susceptible strain, but these differences were not statistically significant and the magnitude was twofold at most. The LD50 values recorded for An. funestus are approximately three-fold higher than those reported elsewhere for other species of anopheline. Monooxygenase based pyrethroid resistance in An. funestus does not influence the toxic effect of chlorfenapyr. It is unlikely that such a small decrease in susceptibility of An. funestus to chlorfenapyr relative to other anophelines would have any operational implications. Chlorfenapyr is an important addition to insecticides available for malaria vector control, and could be used as a resistance management tool to either circumvent or slow the development of resistance.
Ziapour, Seyyed Payman; Kheiri, Sadegh; Asgarian, Fatemeh; Fazeli-Dinan, Mahmoud; Yazdi, Fariborz; Mohammadpour, Reza Ali; Aarabi, Mohsen; Enayati, Ahmadali
Rhipicephalus (Boophilus) annulatus is one of the most important hard ticks parasitizing cattle in northern Iran. The aim of this study was to evaluate pyrethroid resistance levels of this species from Nur County, northern Iran. The hard ticks were collected through a multistage cluster randomized sampling method from the study area and fully engorged female R. (B.) annulatus were reared in a controlled insectary until they produced larvae for bioassay. Seventeen populations of the hard ticks were bioassayed with cypermethrin and 12 populations with lambda-cyhalothrin using a modified larval packet test (LPT). Biochemical assays to measure the contents/activity of different enzyme groups including mixed function oxidases (MFOs), glutathione S-transferases (GSTs) and general esterases were performed. Population 75 showed a resistance ratio of 4.05 with cypermethrin when compared with the most susceptible field population 66 at the LC50 level. With lambda-cyhalothrin the resistance ratio based on LC50 was 3.67 when compared with the susceptible population. The results of biochemical assays demonstrated significantly elevated levels of GSTs and esterases in populations tested compared with the heterozygous susceptible filed population and a correlation coefficient of these enzymes was found in association to lambda-cyhalothrin resistance. Based on the results, pyrethroid acaricides may operationally fail to control R. (B.) annulatus in North of Iran. This study is the first document of pyrethroid resistance in R. (B.) annulatus populations from Iran.
Flores, Adriana E; Ponce, Gustavo; Silva, Brenda G; Gutierrez, Selene M; Bobadilla, Cristina; Lopez, Beatriz; Mercado, Roberto; Black, William C
Seven F1 strains of Aedes aegypti (L.) were evaluated by bottle bioassay for resistance to the pyrethroids d-phenothrin, permethrin, deltamethrin, lambda-cyalothrin, bifenthrin, cypermethrin, alpha-cypermethrin, and z-cypermethrin. The New Orleans strain was used as a susceptible control. Mortality rates after a 1 h exposure and after a 24 h recovery period were determined. The resistance ratio between the 50% knockdown values (RR(KC50)) of the F1 and New Orleans strains indicated high levels of knockdown resistance. The RR(KC50) with alpha-cypermethrin varied from 10 to 100 among strains indicating high levels of knockdown resistance. Most of the strains had moderate resistance to d-phenothrin. Significant but much lower levels of resistance were detected for lambda-cyalothrin, permethrin, and cypermethrin. For zeta-cypermethrin and bifenthrin, only one strain exhibited resistance with RR(KC50) values of 10- and 21-fold, respectively. None of the strains showed RR(KC50) >10 with deltamethrin, and moderate resistance was seen in three strains, while the rest were susceptible. Mosquitoes from all strains exhibited some recovery from all pyrethroids except d-phenothrin. Regression analysis was used to analyze the relationship between RR(LC50) and RR(KC50). Both were highly correlated (R2 = 0.84-0.97) so that the slope could be used to determine how much additional pyrethroid was needed to ensure lethality. Slopes ranged from 0.875 for d-phenothrin (RR(LC50) approximately equal to RR(KC50)) to 8.67 for lambda-cyalothrin (-8.5-fold more insecticide needed to kill). Both RR(LC50) and RR(KC50) values were highly correlated for all pyrethroids except bifenthrin indicating strong cross-resistance. Bifenthrin appears to be an alternative pyrethroid without strong cross-resistance that could be used as an alternative to the current widespread use of permethrin in Mexico.
Full Text Available BACKGROUND: Dengue fever is reemerging on the island of Martinique and is a serious threat for the human population. During dengue epidemics, adult Aedes aegypti control with pyrethroid space sprays is implemented in order to rapidly reduce transmission. Unfortunately, vector control programs are facing operational challenges with the emergence of pyrethroid resistant Ae. aegypti populations. METHODOLOGY/PRINCIPAL FINDINGS: To assess the impact of pyrethroid resistance on the efficacy of treatments, applications of deltamethrin and natural pyrethrins were performed with vehicle-mounted thermal foggers in 9 localities of Martinique, where Ae. aegypti populations are strongly resistant to pyrethroids. Efficacy was assessed by monitoring mortality rates of naturally resistant and laboratory susceptible mosquitoes placed in sentinel cages. Before, during and after spraying, larval and adult densities were estimated. Results showed high mortality rates of susceptible sentinel mosquitoes treated with deltamethrin while resistant mosquitoes exhibited very low mortality. There was no reduction of either larval or adult Ae. aegypti population densities after treatments. CONCLUSIONS/SIGNIFICANCE: This is the first documented evidence that pyrethroid resistance impedes dengue vector control using pyrethroid-based treatments. These results emphasize the need for alternative tools and strategies for dengue control programs.
Zimmer, Christoph T; Müller, Andreas; Heimbach, Udo; Nauen, Ralf
Cabbage stem flea beetle, Psylliodes chrysocephala L. (Coleoptera: Chrysomelidae) is a major pest of winter oilseed rape in several European countries particularly attacking young emerging plants in autumn. Over the last several decades, pyrethroid insecticides have been foliarly applied to control flea beetle outbreaks. Recent control failures in northern Germany suggested pyrethroid resistance development in cabbage stem flea beetles, which were confirmed by resistance monitoring bioassays using lambda-cyhalothrin in an adult vial test. The purpose of this study was to investigate the presence of polymorphisms in the para-type voltage-gated sodium channel gene of P. chrysocephala known to be involved in knock-down resistance (kdr). By using a degenerate primer approach we PCR amplified part of the para-type sodium channel gene and identified in resistant flea beetles a single nucleotide polymorphism resulting in an L1014F (kdr) mutation within domain IIS6 of the channel protein, known as one of the chief pyrethroid target-site resistance mechanisms in several other pest insects. Twenty populations including four archived museum samples collected between 1945 and 1958 were analyzed using a newly developed pyrosequencing diagnostic assay. The assay revealed a kdr allele frequency of 90-100% in those flea beetle populations expressing high-level cross-resistance in discriminating dose bioassays against different pyrethroids such as lambda-cyhalothrin, tau-fluvalinate, etofenprox and bifenthrin. The presence of target-site resistance to pyrethroids in cabbage stem flea beetle is extremely worrying considering the lack of effective alternative modes of action to control this pest in Germany and other European countries, and is likely to result in major control problems once it expands to other geographies. The striking fact that cabbage stem flea beetle is next to pollen beetle, Meligethes aeneus the second coleopteran pest in European winter oilseed rape resisting
Weston, Donald P; Poynton, Helen C; Wellborn, Gary A; Lydy, Michael J; Blalock, Bonnie J; Sepulveda, Maria S; Colbourne, John K
Use of pesticides can have substantial nonlethal impacts on nontarget species, including driving evolutionary change, often with unknown consequences for species, ecosystems, and society. Hyalella azteca, a species complex of North American freshwater amphipods, is widely used for toxicity testing of water and sediment and has frequently shown toxicity due to pyrethroid pesticides. We demonstrate that 10 populations, 3 from laboratory cultures and 7 from California water bodies, differed by at least 550-fold in sensitivity to pyrethroids. The populations sorted into four phylogenetic groups consistent with species-level divergence. By sequencing the primary pyrethroid target site, the voltage-gated sodium channel, we show that point mutations and their spread in natural populations were responsible for differences in pyrethroid sensitivity. At least one population had both mutant and WT alleles, suggesting ongoing evolution of resistance. Although nonresistant H. azteca were susceptible to the typical neurotoxic effects of pyrethroids, gene expression analysis suggests the mode of action in resistant H. azteca was not neurotoxicity but was oxidative stress sustained only at considerably higher pyrethroid concentrations. The finding that a nontarget aquatic species has acquired resistance to pesticides used only on terrestrial pests is troubling evidence of the impact of chronic pesticide transport from land-based applications into aquatic systems. Our findings have far-reaching implications for continued uncritical use of H. azteca as a principal species for monitoring and environmental policy decisions.
An. gambiae from BP areas gave a high level of susceptibility to permethrin with an average mortality of 94%. Molecular analysis identified An. gambiae s.s, and An. arabiensis with a high predominance of An. gambiae s.s (90%. The two molecular forms, M and S, were also determined with a high frequency of the S form (96%. The Kdr gene seemed the main target- site resistance mechanism detected in CCP, TICP, and BP areas at the rates ranging from 32 to 78%. The frequency of ace-1R gene was very low ( The presence of inhibiting factors in soil samples under insecticide treatments were found and affected negatively in delaying the development of An. gambiae larval populations. Conclusions This research shows that Kdr has spread widely in An. gambiae, mainly in CCP and TICP areas where pyrethroids are extensively used. To reduce the negative impact of pesticides use in cotton crop protection, the application of BP-like programs, which do not appear to select for vector resistance would be useful. These results could serve as scientific evidence of the spread of resistance due to a massive agricultural use of insecticides and contribute to the management of pesticides usage on cotton crops hence reducing the selection pressure of insecticides on An. gambiae populations.
Mutunga, James M.; Anderson, Troy D.; Craft, Derek T.; Gross, Aaron D.; Swale, Daniel R.; Tong, Fan; Wong, Dawn M.; Carlier, Paul R.; Bloomquist, Jeffrey R.
Insecticide resistance in the malaria vector, Anopheles gambiae is a serious problem, epitomized by the multi-resistant Akron strain, originally isolated in the country of Benin. Here we report resistance in this strain to pyrethroids and DDT (13-fold to 35-fold compared to the susceptible G3 strain), but surprisingly little resistance to etofenprox, a compound sometimes described as a “pseudo-pyrethroid.” There was also strong resistance to topically-applied commercial carbamates (45-fold to 81-fold), except for the oximes aldicarb and methomyl. Biochemical assays showed enhanced cytochrome P450 monooxygenase and carboxylesterase activity, but not that of glutathione-S-transferase. A series of substituted α,α,α,-trifluoroacetophenone oxime methylcarbamates were evaluated for enzyme inhibition potency and toxicity against G3 and Akron mosquitoes. The compound bearing an unsubstituted phenyl ring showed the greatest toxicity to mosquitoes of both strains. Low cross resistance in Akron was retained by all analogs in the series. Kinetic analysis of acetylcholinesterase activity and its inhibition by insecticides in the G3 strain showed inactivation rate constants greater than that of propoxur, and against Akron enzyme inactivation rate constants similar to that of aldicarb. However, inactivation rate constants against recombinant human AChE were essentially identical to that of the G3 strain. Thus, the acetophenone oxime carbamates described here, though potent insecticides that control resistant Akron mosquitoes, require further structural modification to attain acceptable selectivity and human safety. PMID:26047119
Hong, Shanchao; Guo, Qin; Wang, Weijie; Hu, Shengli; Fang, Fujin; Lv, Yuan; Yu, Jing; Zou, Feifei; Lei, Zhentao; Ma, Kai; Ma, Lei; Zhou, Dan; Sun, Yan; Zhang, Donghui; Shen, Bo; Zhu, Changliang
Pyrethroids are the major class of insecticides used for mosquito control. Excessive and improper use of insecticides, however, has resulted in pyrethroid resistance, which has become a major obstacle for mosquito control. The development of pyrethroid resistance is a complex process involving many genes, and information on post-transcription regulation of pyrethroid resistance is lacking. In this study, we extracted RNA from mosquitoes in various life stages (fourth-instar larvae, pupae, male and female adult mosquitoes) from deltamethrin-sensitive (DS) and resistant (DR) strains. Using illumina sequencing, we obtained 13760296 and 12355472 reads for DS-strains and DR-strains, respectively. We identified 100 conserved miRNAs and 42 novel miRNAs derived from 21 miRNA precursors in Culex pipiens. After normalization, we identified 28 differentially expressed miRNAs between the two strains. Additionally, we found that cpp-miR-71 was significant down regulated in female adults from the DR-strain. Based on microinjection and CDC Bottle Bioassay data, we found that cpp-miR-71 may play a contributing role in deltamethrin resistance. The present study provides the firstly large-scale characterization of miRNAs in Cu. pipiens and provides evidence of post-transcription regulation. The differentially expressed miRNAs between the two strains are expected to contribute to the development of pyrethroid resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.
Hassan Vatandoost; Ahmad Ali Hanafi-Bojd
Objective:To investiagte insecticide resistance in target species for better insecticide resistance managemnet in malaria control programs.Methods:The status of insecticide resistance to different imagicides inAnopheles stephensi(An. stephensi) includingDDT4%, lambdacyhalothrin 0.50%, deltamethrin0.05%, permethrin0.75%, cyfluthrin0.15% and etofenprox0.50% was performed according toWHO standard method.Results:The mortality rate to lambdacyhalothrin, permethrin, cyfluthrin, deltamethrin, etofenprox andDDT was(88.0±3.2),(92.0±2.7),(52.0±5.0),(96.0±2.2),(90.0±3.0) and(41.0±5.7) percent, respectively at diagnostic dose for one hour exposure time followed by24 h recovery period.Conclusions:These results showed first indication of pyrethroid resistance inAn. stephensiin a malarious area, from southernIran.There is widespread, multiple resistances in the country inAn. stephensi to organochlorine and some report of tolerance to organophosphate insecticides and recently to pyrethroids.However, results of this paper will provide a clue for monitoring and mapping of insecticide resistance in the main malaria vector for implementation of any vector control.
Emmanuel A Temu
Full Text Available BACKGROUND: Long Lasting Insecticidal Nets (LLIN and Indoor Residual Spraying (IRS have both proven to be effective malaria vector control strategies in Africa and the new technology of insecticide treated durable wall lining (DL is being evaluated. Sustaining these interventions at high coverage levels is logistically challenging and, furthermore, the increase in insecticide resistance in African malaria vectors may reduce the efficacy of these chemical based interventions. Monitoring of vector populations and evaluation of the efficacy of insecticide based control approaches should be integral components of malaria control programmes. This study reports on entomological survey conducted in 2011 in Bomi County, Liberia. METHODS: Anopheles gambiae larvae were collected from four sites in Bomi, Liberia, and reared in a field insectary. Two to five days old female adult An gambiae s.l. were tested using WHO tube (n=2027 and cone (n=580 bioassays in houses treated with DL or IRS. A sample of mosquitoes (n=169 were identified to species/molecular form and screened for the presence of knock down resistance (kdr alleles associated with pyrethroid resistance. RESULTS: Anopheles gambiae s.l tested were resistant to deltamethrin but fully susceptible to bendiocarb and fenithrothion. The corrected mortality of local mosquitoes exposed to houses treated with deltamethrin either via IRS or DL was 12% and 59% respectively, suggesting that resistance may affect the efficacy of these interventions. The presence of pyrethroid resistance was associated with a high frequency of the 1014F kdr allele (90.5% although this mutation alone cannot explain the resistance levels observed. CONCLUSION: High prevalence of resistance to deltamethrin in Bomi County may reduce the efficacy of malaria strategies relying on this class of insecticide. The findings highlight the urgent need to expand and sustain monitoring of insecticide resistance in Liberian malaria vectors
Emerging insecticide resistance is a major issue for vector control; it decreases effectiveness of insecticides, thereby requiring greater quantities for comparable control with a net increase in risk of disease resurgence, product cost, and damage risk to the ecosystem. Pyrethroid resistance has b...
Aedes aegypti is an efficient vector of a number of diseases that affect man and is of increasing concern because of the reemergence of dengue and recent identification of locally acquired chikungunya in Florida. Pesticide resistance in this species has been demonstrated in several neighboring coun...
Full Text Available BACKGROUND: Alternative compounds which can complement pyrethroids on long-lasting insecticidal nets (LN in the control of pyrethroid resistant malaria vectors are urgently needed. Pyriproxyfen (PPF, an insect growth regulator, reduces the fecundity and fertility of adult female mosquitoes. LNs containing a mixture of pyriproxyfen and pyrethroid could provide personal protection through the pyrethroid component and reduce vector abundance in the next generation through the sterilizing effect of pyriproxyfen. METHOD: The efficacy of Olyset Duo, a newly developed mixture LN containing pyriproxyfen and permethrin, was evaluated in experimental huts in southern Benin against pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus. Comparison was made with Olyset Net® (permethrin alone and a LN with pyriproxyfen alone (PPF LN. Laboratory tunnel tests were performed to substantiate the findings in the experimental huts. RESULTS: Overall mortality of wild pyrethroid resistant An. gambiae s.s. was significantly higher with Olyset Duo than with Olyset Net (50% vs. 27%, P = 0.01. Olyset DUO was more protective than Olyset Net (71% vs. 3%, P<0.001. The oviposition rate of surviving blood-fed An. gambiae from the control hut was 37% whereas none of those from Olyset Duo and PPF LN huts laid eggs. The tunnel test results were consistent with the experimental hut results. Olyset Duo was more protective than Olyset Net in the huts against wild pyrethroid resistant Cx. quinquefasciatus although mortality rates of this species did not differ significantly between Olyset Net and Olyset Duo. There was no sterilizing effect on surviving blood-fed Cx. quinquefasciatus with the PPF-treated nets. CONCLUSION: Olyset Duo was superior to Olyset Net in terms of personal protection and killing of pyrethroid resistant An. gambiae, and sterilized surviving blood-fed mosquitoes. Mixing pyrethroid and pyriproxyfen on a LN shows potential for malaria control and
Lipiński, Zbigniew; Szubstarski, Jarosław; Szubstarska, Dagna
The aim of our current study was to investigate the possible occurence of pyrethroid (taufluvalinate) resistant Varroa mites infestations in 24 randomly chosen apiaries of Warmia-Mazury province of northeast Poland. The methodology used for the analysis of resistant Varroa strains strictly followed the protocol described by Milani. We identified 3 apiaries that were infested with high risk pyrethroid resistance mites and a further 9 apiaries that were free from this resitance. The brood samples collected from the remaining apiaries did not contain sufficient numbers of parasites to enable us to properly perform the assay. Our finding that 25% of the tested brood samples showed a high risk of fully pyrethroid resistant Varroa mite contamination indicates that resistant Varroa may become wide spread in apiaries in Poland. Interestingly these high risk resistant mites were found in honeybee colonies with low levels of Varroa infestation, with an average rate of 2.16%. We also discuss the role of amitraz (amidine) in the phenomenon of Varroa resistance to pyrethroids.
Full Text Available Abstract Background Pyrethroid insecticides are widely used for insect pest control in Cameroon. In certain insect species, particularly the malaria vector Anopheles gambiae, resistance to this class of insecticides is a source of great concern and needs to be monitored in order to sustain the efficacy of vector control operations in the fields. This study highlights trends in DDT and pyrethroid resistance in wild An. gambiae populations from South Cameroon. Methods Mosquitoes were collected between 2001 and 2007 in four sites in South Cameroon, where insecticides are used for agricultural or personal protection purposes. Insecticide use was documented in each site by interviewing residents. Batches of 2-4 days old adult female mosquitoes reared from larval collections were tested for susceptibility to DDT, permethrin and deltamethrin using standard WHO procedures. Control, dead and survivors mosquitoes from bioassays were identified by PCR-RFLP and characterized for the kdr mutations using either the AS-PCR or the HOLA method. Results Four chemical insecticide groups were cited in the study sites: organochlorines, organophosphates, carbamates and pyrethroids. These chemicals were used for personal, crop or wood protection. In the four An. gambiae populations tested, significant variation in resistance levels, molecular forms composition and kdr frequencies were recorded in the time span of the study. Increases in DDT and pyrethroid resistance, as observed in most areas, were generally associated with an increase in the relative frequency of the S molecular form carrying the kdr mutations at higher frequencies. In Mangoum, however, where only the S form was present, a significant increase in the frequency of kdr alleles between 2003 to 2007 diverged with a decrease of the level of resistance to DDT and pyrethroids. Analyses of the kdr frequencies in dead and surviving mosquitoes showed partial correlation between the kdr genotypes and resistance
Fiacre R Agossa
Full Text Available Since the first evidence of pyrethroids resistance in 1999 in Benin, mutations have rapidly increased in mosquitoes and it is now difficult to design a study including a control area where malaria vectors are fully susceptible. Few studies have assessed the after effect of resistance on the success of pyrethroid based prevention methods in mosquito populations. We therefore assessed the impact of resistance on the effectiveness of pyrethroids based indoor residual spraying (IRS in semi-field conditions and long lasting insecticidal nets (LLINs in laboratory conditions. The results observed showed low repulsion and low toxicity of pyrethroids compounds in the test populations. The toxicity of pyrethroids used in IRS was significantly low with An. gambiae s.l (< 46% but high for other predominant species such as Mansonia africana (93% to 97%. There were significant differences in terms of the repellent effect expressed as exophily and deterrence compared to the untreated huts (P<0.001. Furthermore, mortality was 23.71% for OlyseNet® and 39.06% for PermaNet®. However, with laboratory susceptible "Kisumu", mortality was 100% for both nets suggesting a resistance within the wild mosquito populations. Thus treatment with pyrethroids at World Health Organization recommended dose will not be effective at reducing malaria in the coming years. Therefore it is necessary to study how insecticide resistance decreases the efficacy of particular pyrethroids used in pyrethroid-based vector control so that a targeted approach can be adopted.
Ibrahim, Sulaiman S.; Riveron, Jacob M.; Stott, Robert; Irving, Helen; Wondji, Charles S.
Pyrethroid insecticides are the front line vector control tools used in bed nets to reduce malaria transmission and its burden. However, resistance in major vectors such as Anopheles arabiensis is posing a serious challenge to the success of malaria control. Herein, we elucidated the molecular and biochemical basis of pyrethroid resistance in a knockdown resistance-free Anopheles arabiensis population from Chad, Central Africa. Using heterologous expression of P450s in Escherichia coli coupled with metabolism assays we established that the over-expressed P450 CYP6P4, located in the major pyrethroid resistance (rp1) quantitative trait locus (QTL), is responsible for resistance to Type I and Type II pyrethroid insecticides, with the exception of deltamethrin, in correlation with field resistance profile. However, CYP6P4 exhibited no metabolic activity towards non-pyrethroid insecticides, including DDT, bendiocarb, propoxur and malathion. Combining fluorescent probes inhibition assays with molecular docking simulation, we established that CYP6P4 can bind deltamethrin but cannot metabolise it. This is possibly due to steric hindrance because of the large vdW radius of bromine atoms of the dihalovinyl group of deltamethrin which docks into the heme catalytic centre. The establishment of CYP6P4 as a partial pyrethroid resistance gene explained the observed field resistance to permethrin, and its inability to metabolise deltamethrin probably explained the high mortality from deltamethrin exposure in the field populations of this Sudano-Sahelian An. arabiensis. These findings describe the heterogeneity in resistance towards insecticides, even from the same class, highlighting the need to thoroughly understand the molecular basis of resistance before implementing resistance management/control tools. PMID:26548743
Ibrahim, Sulaiman S; Riveron, Jacob M; Stott, Robert; Irving, Helen; Wondji, Charles S
Pyrethroid insecticides are the front line vector control tools used in bed nets to reduce malaria transmission and its burden. However, resistance in major vectors such as Anopheles arabiensis is posing a serious challenge to the success of malaria control. Herein, we elucidated the molecular and biochemical basis of pyrethroid resistance in a knockdown resistance-free Anopheles arabiensis population from Chad, Central Africa. Using heterologous expression of P450s in Escherichia coli coupled with metabolism assays we established that the over-expressed P450 CYP6P4, located in the major pyrethroid resistance (rp1) quantitative trait locus (QTL), is responsible for resistance to Type I and Type II pyrethroid insecticides, with the exception of deltamethrin, in correlation with field resistance profile. However, CYP6P4 exhibited no metabolic activity towards non-pyrethroid insecticides, including DDT, bendiocarb, propoxur and malathion. Combining fluorescent probes inhibition assays with molecular docking simulation, we established that CYP6P4 can bind deltamethrin but cannot metabolise it. This is possibly due to steric hindrance because of the large vdW radius of bromine atoms of the dihalovinyl group of deltamethrin which docks into the heme catalytic centre. The establishment of CYP6P4 as a partial pyrethroid resistance gene explained the observed field resistance to permethrin, and its inability to metabolise deltamethrin probably explained the high mortality from deltamethrin exposure in the field populations of this Sudano-Sahelian An. arabiensis. These findings describe the heterogeneity in resistance towards insecticides, even from the same class, highlighting the need to thoroughly understand the molecular basis of resistance before implementing resistance management/control tools.
Full Text Available Introduction & Objectives: A laboratory study was carried out to investigate the insecticidal, irritant and anti-feeding effects of nets treated with various pyrethroids against susceptible and highly pyrethroid resistant strains of An. stephensi. Materials & Methods: Tests were carried out inside a mosquito cage measuring 25×25×25 cm where mosquitoes were offered the opportunity to feed blood on an arm through the top face of the cage which had been pyrethroid treated.Results: With all the pyrethroids tested, the resistant strain spent a longer time in contact with a treated net, which was in contact with a human arm, than did the susceptible strain. With permethrin the resistant strain fed significantly more successfully through the treated netting than did the susceptible strain. With deltamethrin there was a non-significant tendency in the same direction in comparing the two strains. However, with alphacypermethrin there was a non-significant tendency in the reverse direction. After 15 min in the cage which tested for the ability to feed through a pyrethroid treated net, observed mortality was higher with the susceptible than the resistant strain. Conclusion: Thus there was no sign that the longer resting of the resistant strain on treated netting would compensate for the fact that a higher dose was needed to kill this strain. Such compensation had been suggested with the West African An. gambiae where treated nets continue to work well against a highly resistant wild population. However this does not seem to apply to our resistant An. stephens.
González-Cabrera, Joel; Rodríguez-Vargas, Sonia; Davies, T. G. Emyr; Field, Linda M.; Schmehl, Daniel; Ellis, James D.; Krieger, Klemens; Williamson, Martin S.
The parasitic mite Varroa destructor has a significant worldwide impact on bee colony health. In the absence of control measures, parasitized colonies invariably collapse within 3 years. The synthetic pyrethroids tau-fluvalinate and flumethrin have proven very effective at managing this mite within apiaries, but intensive control programs based mainly on one active ingredient have led to many reports of pyrethroid resistance. In Europe, a modification of leucine to valine at position 925 (L925V) of the V. destructor voltage-gated sodium channel was correlated with resistance, the mutation being found at high frequency exclusively in hives with a recent history of pyrethroid treatment. Here, we identify two novel mutations, L925M and L925I, in tau-fluvalinate resistant V. destructor collected at seven sites across Florida and Georgia in the Southeastern region of the USA. Using a multiplexed TaqMan® allelic discrimination assay, these mutations were found to be present in 98% of the mites surviving tau-fluvalinate treatment. The mutations were also found in 45% of the non-treated mites, suggesting a high potential for resistance evolution if selection pressure is applied. The results from a more extensive monitoring programme, using the Taqman® assay described here, would clearly help beekeepers with their decision making as to when to include or exclude pyrethroid control products and thereby facilitate more effective mite management programmes. PMID:27191597
Full Text Available The parasitic mite Varroa destructor has a significant worldwide impact on bee colony health. In the absence of control measures, parasitized colonies invariably collapse within 3 years. The synthetic pyrethroids tau-fluvalinate and flumethrin have proven very effective at managing this mite within apiaries, but intensive control programs based mainly on one active ingredient have led to many reports of pyrethroid resistance. In Europe, a modification of leucine to valine at position 925 (L925V of the V. destructor voltage-gated sodium channel was correlated with resistance, the mutation being found at high frequency exclusively in hives with a recent history of pyrethroid treatment. Here, we identify two novel mutations, L925M and L925I, in tau-fluvalinate resistant V. destructor collected at seven sites across Florida and Georgia in the Southeastern region of the USA. Using a multiplexed TaqMan® allelic discrimination assay, these mutations were found to be present in 98% of the mites surviving tau-fluvalinate treatment. The mutations were also found in 45% of the non-treated mites, suggesting a high potential for resistance evolution if selection pressure is applied. The results from a more extensive monitoring programme, using the Taqman® assay described here, would clearly help beekeepers with their decision making as to when to include or exclude pyrethroid control products and thereby facilitate more effective mite management programmes.
Srivastava Harish C
Full Text Available Abstract Background Malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. Hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. In the present study, chlorfenapyr was evaluated against Anopheles culicifacies and Anopheles stephensi for its possible use in vector control. Methods Efficacy of chlorfenapyr against An. culicifacies and An. stephensi was assessed using adult bioassay tests. In the laboratory, determination of diagnostic dose, assessment of residual activity on different substrates, cross-resistance pattern with different insecticides and potentiation studies using piperonyl butoxide were undertaken by following standard procedures. Potential cross-resistance patterns were assessed on field populations of An. culicifacies. Results A dose of 5.0% chlorfenapyr was determined as the diagnostic concentration for assessing susceptibility applying the WHO tube test method in anopheline mosquitoes with 2 h exposure and 48 h holding period. The DDT-resistant/malathion-deltamethrin-susceptible strain of An. culicifacies species C showed higher LD50 and LD99 (0.67 and 2.39% respectively values than the DDT-malathion-deltamethrin susceptible An. culicifacies species A (0.41 and 2.0% respectively and An. stephensi strains (0.43 and 2.13% respectively and there was no statistically significant difference in mortalities among the three mosquito species tested (p > 0.05. Residual activity of chlorfenapyr a.i. of 400 mg/m2 on five fabricated substrates, namely wood, mud, mud+lime, cement and cement + distemper was found to be effective up to 24 weeks against An. culicifacies and up to 34 weeks against An. stephensi. No cross-resistance to DDT, malathion, bendiocarb and deltamethrin was observed with chlorfenapyr in laboratory-reared strains of An. stephensi and field-caught An. culicifacies
Raghavendra, Kamaraju; Barik, Tapan K; Sharma, Poonam; Bhatt, Rajendra M; Srivastava, Harish C; Sreehari, Uragayala; Dash, Aditya P
Malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. Hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. In the present study, chlorfenapyr was evaluated against Anopheles culicifacies and Anopheles stephensi for its possible use in vector control. Efficacy of chlorfenapyr against An. culicifacies and An. stephensi was assessed using adult bioassay tests. In the laboratory, determination of diagnostic dose, assessment of residual activity on different substrates, cross-resistance pattern with different insecticides and potentiation studies using piperonyl butoxide were undertaken by following standard procedures. Potential cross-resistance patterns were assessed on field populations of An. culicifacies. A dose of 5.0% chlorfenapyr was determined as the diagnostic concentration for assessing susceptibility applying the WHO tube test method in anopheline mosquitoes with 2 h exposure and 48 h holding period. The DDT-resistant/malathion-deltamethrin-susceptible strain of An. culicifacies species C showed higher LD50 and LD99 (0.67 and 2.39% respectively) values than the DDT-malathion-deltamethrin susceptible An. culicifacies species A (0.41 and 2.0% respectively) and An. stephensi strains (0.43 and 2.13% respectively) and there was no statistically significant difference in mortalities among the three mosquito species tested (p > 0.05). Residual activity of chlorfenapyr a.i. of 400 mg/m2 on five fabricated substrates, namely wood, mud, mud+lime, cement and cement + distemper was found to be effective up to 24 weeks against An. culicifacies and up to 34 weeks against An. stephensi. No cross-resistance to DDT, malathion, bendiocarb and deltamethrin was observed with chlorfenapyr in laboratory-reared strains of An. stephensi and field-caught An. culicifacies. Potentiation studies demonstrated the antagonistic
BACKGROUND: Pyrethroids are increasingly used to block the transmission of diseases spread by Aedes aegypti such as dengue and yellow fever. However, insecticide resistance poses a serious threat, thus there is an urgent need to identify the genes and proteins associated with pyrethroid resistance in order to produce effective counter measures. In Ae. aegypti, overexpression of P450s such as the CYP9J32 gene have been linked with pyrethroid resistance. Our aim was to confirm the role of CYP9J...
Pietrantonio, P V; Junek, T A; Parker, R; Mott, D; Siders, K; Troxclair, N; Vargas-Camplis, J; Westbrook, J K; Vassiliou, V A
The bollworm, Helicoverpa zea (Boddie), is a key pest of cotton in Texas. Bollworm populations are widely controlled with pyrethroid insecticides in cotton and exposed to pyrethroids in other major crops such as grain sorghum, corn, and soybeans. A statewide program that evaluated cypermethrin resistance in male bollworm populations using an adult vial test was conducted from 2003 to 2006 in the major cotton production regions of Texas. Estimated parameters from the most susceptible field population currently available (Burleson County, September 2005) were used to calculate resistance ratios and their statistical significance. Populations from several counties had statistically significant (P Nueces County in 2004, and Williamson and Uvalde Counties in 2005. These findings explain the observed pyrethroid control failures in various counties in Texas. Based on the assumption that resistance is caused by a single gene, the Hardy-Weinberg equilibrium formula was used for estimation of frequencies for the putative resistant allele (q) using 3 and 10 microg/vial as discriminatory dosages for susceptible and heterozygote resistant insects, respectively. The influence of migration on local levels of resistance was estimated by analysis of wind trajectories, which partially clarifies the rapid evolution of resistance to cypermethrin in bollworm populations. This approach could be used in evaluating resistance evolution in other migratory pests.
Reimer, Lisa; Fondjo, Etienne; Patchoké, Salomon; Diallo, Brehima; Lee, Yoosook; Ng, Arash; Ndjemai, Hamadou M; Atangana, Jean; Traore, Sekou F; Lanzaro, Gregory; Cornel, Anthony J
The spread of insecticide resistance genes in Anopheles gambiae Giles sensu stricto threatens to compromise vector-based malaria control programs. Two mutations at the same locus in the voltage-gated sodium channel gene are known to confer knockdown resistance (kdr) to pyrethroids and DDT. Kdr-e involves a leucine-serine substitution, and it was until recently thought to be restricted to East Africa, whereas kdr-w, which involves a leucine-phenylalanine substitution, is associated with resistance in West Africa. In this study, we analyze the frequency and relationship between the kdr genotypes and resistance to type I and type II pyrethroids and DDT by using WHO test kits in both the Forest-M and S molecular forms of An. gambiae in Cameroon. Both kdr-w and kdr-e polymorphisms were found in sympatric An. gambiae, and in many cases in the same mosquito. Kdr-e and kdr-w were detected in both forms, but they were predominant in the S form. Both kdr-e and kdr-w were closely associated with resistance to DDT and weakly associated with resistance to type II pyrethroids. Kdr-w conferred greater resistance to permethrin than kdr-e. We also describe a modified diagnostic designed to detect both resistant alleles simultaneously.
Muggelberg, Leslie L; Huff Hartz, Kara E; Nutile, Samuel A; Harwood, Amanda D; Heim, Jennifer R; Derby, Andrew P; Weston, Donald P; Lydy, Michael J
The recent discovery of pyrethroid-resistant Hyalella azteca populations in California, USA suggests there has been significant exposure of aquatic organisms to these terrestrially-applied insecticides. Since resistant organisms are able to survive in relatively contaminated habitats they may experience greater pyrethroid bioaccumulation, subsequently increasing the risk of those compounds transferring to predators. These issues were evaluated in the current study following toxicity tests in water with permethrin which showed the 96-h LC50 of resistant H. azteca (1670 ng L(-1)) was 53 times higher than that of non-resistant H. azteca (31.2 ng L(-1)). Bioaccumulation was compared between resistant and non-resistant H. azteca by exposing both populations to permethrin in water and then measuring the tissue concentrations attained. Our results indicate that resistant and non-resistant H. azteca have similar potential to bioaccumulate pyrethroids at the same exposure concentration. However, significantly greater bioaccumulation occurs in resistant H. azteca at exposure concentrations non-resistant organisms cannot survive. To assess the risk of pyrethroid trophic transfer, permethrin-dosed resistant H. azteca were fed to fathead minnows (Pimephales promelas) for four days, after which bioaccumulation of permethrin and its biotransformation products in fish tissues were measured. There were detectable concentrations of permethrin in fish tissues after they consumed dosed resistant H. azteca. These results show that bioaccumulation potential is greater in organisms with pyrethroid resistance and this increases the risk of trophic transfer when consumed by a predator. The implications of this study extend to individual fitness, populations and food webs.
Tong, Hong; Su, Qi; Zhou, Xiaomao; Bai, Lianyang
The present studies were carried out to evaluate resistance in the populations of Spodoptera litura Fab. (Lepidoptera, Noctuidae) from five districts of Hunan Province in China to various insecticides from 2010 to 2012 using a standard leaf dip bioassay method. For organophosphates and pyrethroids, resistance ratios compared with a susceptible Lab-BJ strain were in the range of 14-229-fold for organophosphates and 12-227-fold for pyrethroids. Similarly, relative low levels of resistance to emamectin, indoxacarb, and chlorfenapyr were observed in all five populations. In contrast, the resistance to carbamates (thiodicarb or methomyl) was significantly higher than that of organophosphates, pyrethroids and newer chemistry insecticides. The pairwise correlation coefficients of LC50 values indicated that the newer chemistry insecticides and old generation insecticides were not significant except abamectin, which was negatively significantly correlated with methomyl. A significant correlation was observed between thiodicarb, methomyl, and deltamethrin, whereas resistance to bifenthrin showed no correlations with resistance to other insecticides except deltamethrin. The results are discussed in relation to integrated pest management for S. litura with special reference to management of field evolved resistance to insecticides.
Julie-Anne A Tangena
Full Text Available BACKGROUND: Malaria vector control is threatened by resistance to pyrethroids, the only class of insecticides used for treating bed nets. The second major vector control method is indoor residual spraying with pyrethroids or the organochloride DDT. However, resistance to pyrethroids frequently confers resistance to DDT. Therefore, alternative insecticides are urgently needed. METHODOLOGY/PRINCIPAL FINDINGS: Insecticide resistance and the efficacy of indoor residual spraying with different insecticides was determined in a Gambian village. Resistance of local vectors to pyrethroids and DDT was high (31% and 46% mortality, respectively while resistance to bendiocarb and pirimiphos methyl was low (88% and 100% mortality, respectively. The vectors were predominantly Anopheles gambiae s.s. with 94% of them having the putative resistant genotype kdr 1014F. Four groups of eight residential compounds were each sprayed with either (1 bendiocarb, a carbamate, (2 DDT, an organochlorine, (3 microencapsulated pirimiphos methyl, an organophosphate, or (4 left unsprayed. All insecticides tested showed high residual activity up to five months after application. Mosquito house entry, estimated by light traps, was similar in all houses with metal roofs, but was significantly less in IRS houses with thatched roofs (p=0.02. Residents participating in focus group discussions indicated that IRS was considered a necessary nuisance and also may decrease the use of long-lasting insecticidal nets. CONCLUSION/SIGNIFICANCE: Bendiocarb and microencapsulated pirimiphos methyl are viable alternatives for indoor residual spraying where resistance to pyrethroids and DDT is high and may assist in the management of pyrethroid resistance.
Samra, Aman I; Kamita, Shizuo G; Yao, Hong-Wei; Cornel, Anthony J; Hammock, Bruce D
BACKGROUND The Marin strain of Culex pipiens Say is a pyrethroid-resistant population that was collected in Marin County, California, in 2001 and subsequently maintained in the laboratory under regular permethrin exposure. RESULTS In this study, two genes, CpGSTd1 and CpGSTd2, encoding glutathione S-transferase (GST) were cloned from Cx. pipiens Marin. Phylogenetic analysis of the deduced amino acid sequences, CpGSTD1 and CpGSTD2, of these genes indicated that they belong to the Delta class of insect GSTs. The nucleotide and deduced amino acid sequences of CpGSTd1 and CpGSTd2 were 59% and 48% identical, respectively. CpGSTD1 and CpGSTD2 were expressed in Escherichia coli and purified by affinity chromatography. The recombinant GSTs exhibited unique selectivity towards the general GST substrates CDNB and DCNB, and also differed in their sensitivity to known inhibitors of GSTs. CpGSTD1 exhibited peroxidase activity with cumene hydroperoxide, while CpGSTD2 appeared to lack this activity. CpGSTD1 was able to metabolize DDT, while DDT metabolism by CpGSTD2 was not detectable. CpGSTD1 and CpGSTD2 showed no detectable metabolism of permethrin. Gene expression of CpGSTd1 and CpGSTd2 in Marin mosquitoes was elevated by about 2-fold in comparison to that found in a pyrethroid-sensitive mosquito strain. CONCLUSION Our results indicated that CpGSTD1 and CpGSTD2 have unique biochemical characteristics but they did not appear to play major roles in permethrin resistance in Marin mosquitoes. PMID:22290868
Kilpinen, Ole; Kristensen, Michael; Jensen, Karl-Martin Vagn
Bed bug, Cimex lectularius L., populations were investigated for resistance against permethrin and chlorpyrifos in a topical application bioassay, after an initial establishment of a discriminating dose with a susceptible population. For both insecticides, ca. two times the lethal dose LD(99) was selected: 2,560 ng of permethrin and 200 ng of chlorpyrifos per bed bug, respectively. Bed bugs were collected from infested homes in Denmark at ten locations and bred in the laboratory. The frequency of permethrin-resistant individuals was high in Danish bed bug populations as susceptible individuals were only found in three of ten populations. In contrast, the frequency of chlorpyrifos-resistant individuals was low in Danish bed bug populations, but resistant individuals were found in five of ten populations. To test the significance of the observed resistance, we performed tarsal contact test with commercially available insecticides. The test indicated that both a permethrin and a deltamethrin product had very low efficacy against the field-collected bed bug populations. Despite the reduced sensitivity to synthetic pyrethroids, all populations tested in the tarsal test on the commercial product with micro-encapsulated chlorpyrifos resulted in close to 100% mortality.
Qayyum, Mirza Abdul; Wakil, Waqas; Arif, Muhammad Jalal; Sahi, Shahbaz Talib; Saeed, Noor Abid; Russell, Derek Allan
Field populations of Helicoverpa armigera Hübner from 15 localities across the Punjab, Pakistan, were assessed by the leaf dip method for resistance against formulated organophosphates, pyrethroids, and newer insecticide groups. Resistance levels in H. armigera have been incrementally increasing for organophosphate and pyrethroid insecticides after decades of use in Pakistan. Resistance ratios (RRs) documented for organophosphates were 24- to 116-fold for profenofos and 22- to 87-fold for chlorpyrifos. For pyrethroids, RRs were 3- to 69-fold for cypermethrin and 3- to 27-fold for deltamethrin. Resistance levels against newer chemistries were 2- to 24-fold for chlorfenapyr, 1- to 22-fold for spinosad, 1- to 20-fold for indoxacarb, 1- to 18-fold for abamectin, and 1- to 16-fold for emamectin benzoate. Resistant populations of H. armigera were mainly in the southern part of the Punjab, Pakistan. The most resistant populations were collected from Pakpattan, Multan, and Muzzafargarh. Of the nine insecticides tested, LC50 and LC90 values were lower for newer insecticide groups; resistance levels were moderate to very high against organophosphates, very low to high against pyrethroids, and very low to low against the newer-chemistry insecticides. These findings suggest that the newer-chemistry insecticides with different modes of action could be included in insecticide rotations or replace the older insecticides. Supplementing the use of synthetic insecticides with safer alternatives could help to successfully lower the farmer's reliance on insecticides and the incidence of resistance due to repeated use of insecticides against major insect pests. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: email@example.com.
Breckenridge, Charles B; Holden, Larry; Sturgess, Nicholas; Weiner, Myra; Sheets, Larry; Sargent, Dana; Soderlund, David M; Choi, Jin-Sung; Symington, Steve; Clark, J Marshall; Burr, Steve; Ray, David
an outlier when the MDS maps were based on calcium influx/glutamate release potency. Four of six alpha-cyano pyrethroids (lambda-cyfluthrin, cypermethrin, deltamethrin and fenpropathrin) reduced open chloride channel probability. The R-isomers of lambda-l-cyhalothrin reduced open channel probability whereas the S-isomers, antagonized the action of the R-isomers. None of the non-cyano pyrethroids reduced open channel probability, except bioallethrin, which gave a weak response. Overall, based upon neurotoxicity data and the effect of pyrethroids on sodium, calcium and chloride ion channels, it is proposed that bioallethrin, cismethrin, tefluthrin, bifenthrin and permethrin belong to one common mechanism group and deltamethrin, lambda-cyhalothrin, cyfluthrin and cypermethrin belong to a second. Fenpropathrin and esfenvalerate occupy an intermediate position between these two groups.
Full Text Available The aim of the currrent investigation was to evaluate (a the toxicity of three pyrethroids (deltamethrin, lambda-cyhalothrin, and tetramethrin; (b the effect of these insecticides on the locomotor activity; and (c the repellent effect of N,N-diethyl-m-toluamide (DEET on two deltamethrin-resistant strains of Triatoma infestans from Argentina (El Chorro and La Toma, and one susceptible strain. The resistance ratios (RRs obtained for the La Toma strain were: > 10,769, 50.7, and > 5.2 for deltamethrin, lambda-cyhalothrin, and tetramethrin respectively. The RRs for the El Chorro strain were: > 10,769, 85.8, and > 5.2 for deltamethrin, lambda-cyhalothrin, and tetramethrin respectively. The hyperactivity usually caused by the three pyrethroids was in both the deltamethrin-resistant strains compared to the susceptible reference strain. No differences were observed in the repellent effect of DEET between the three groups. These results indicate that the deltamethrin-resistant insects have a cross resistance to lambda-cyhalothrin and tetramethrin, and are also resistant to the first symptom of pyrethroid poisoning (hyperactivity. However, the sensorial process related to DEET repellency does not appear to be altered.
Itokawa, Kentaro; Komagata, Osamu; Kasai, Shinji; Ogawa, Kohei; Tomita, Takashi
Recently-emerging genome editing technologies have enabled targeted gene knockout experiments even in non-model insect species. For studies on insecticide resistance, genome editing technologies offer some advantages over the conventional reverse genetic technique, RNA interference, for testing causal relationships between genes of detoxifying enzymes and resistance phenotypes. There were relatively abundant evidences indicating that the overexpression of a cytochrome P450 gene CYP9M10 confers strong pyrethroid resistance in larvae of the southern house mosquito Culex quinquefasciatus. However, reverse genetic verification has not yet been obtained because of the technical difficulty of microinjection into larvae. Here, we tested two genome editing technologies, transcription activator-like effector nucleases (TALEN)s and clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), to disrupt CYP9M10 in a resistant strain of C. quinquefasciatus. Additionally, we developed a novel, effective approach to construct a TALE using the chemical cleavage of phosphorothioate inter-nucleotide linkages in the level 1 assembly. Both TALEN and CRISPR/Cas9 induced frame-shifting mutations in one or all copies of CYP9M10 in a pyrethroid-resistant strain. A line fixed with a completely disrupted CYP9M10 haplotype showed more than 100-fold reduction in pyrethroid resistance in the larval stage.
Okia, Michael; Ndyomugyenyi, Richard; Kirunda, James; Byaruhanga, Anatol; Adibaku, Seraphine; Lwamafa, Denis K; Kironde, Fred
Background There are major concerns over sustaining the efficacy of current malaria vector control interventions given the rapid spread of resistance, particularly to pyrethroids. This study assessed the bioefficacy of five WHO-recommended long-lasting insecticidal nets (LLINs) against pyrethroid-resistant Anopheles gambiae field populations from Uganda. Methods Adult An. gambiae from Lira, Tororo, Wakiso and Kanungu districts were exposed to permethrin (0.75%) or deltamethrin (0.05%) in stan...
Seong, Keon Mook; Lee, Da-Young; Yoon, Kyong Sup; Kwon, Deok Ho; Kim, Heung Chul; Klein, Terry A; Clark, J Marshall; Lee, Si Hyeock
Two point mutations (V419L and L925I) in the voltage-sensitive sodium channel alpha-subunit gene have been identified in deltamethrin-resistant bed bugs. A quantitative sequencing (QS) protocol was developed to establish a population-based genotyping method as a molecular resistance-monitoring tool based on the frequency of the two mutations. The nucleotide signal ratio at each mutation site was generated from sequencing chromatograms and plotted against the corresponding resistance allele frequency. Frequency prediction equations were generated from the plots by linear regression, and the signal ratios were shown to highly correlate with resistance allele frequencies (r2 > 0.9928). As determined by QS, neither mutation was found in a bed bug population collected in 1993. Populations collected in recent years (2007-2009), however, exhibited completely or nearly saturating L925I mutation frequencies and highly variable frequencies of the V419L mutation. In addition to QS, the filter contact vial bioassay (FCVB) method was established and used to determine the baseline susceptibility and resistance of bed bugs to deltamethrin and lambda-cyhalothrin. A pyrethroid-resistant strain showed >9,375- and 6,990-fold resistance to deltamethrin and lambda-cyhalothrin, respectively. Resistance allele frequencies in different bed bug populations predicted by QS correlated well with the FCVB results, confirming the roles of the two mutations in pyrethroid resistance. Taken together, employment of QS in conjunction with FCVB should greatly facilitate the detection and monitoring of pyrethroid-resistant bed bugs in the field. The advantages of FCVB as an on-site resistance-monitoring tool are discussed.
Bradley J Stevenson
Full Text Available BACKGROUND: Pyrethroids are increasingly used to block the transmission of diseases spread by Aedes aegypti such as dengue and yellow fever. However, insecticide resistance poses a serious threat, thus there is an urgent need to identify the genes and proteins associated with pyrethroid resistance in order to produce effective counter measures. In Ae. aegypti, overexpression of P450s such as the CYP9J32 gene have been linked with pyrethroid resistance. Our aim was to confirm the role of CYP9J32 and other P450s in insecticide metabolism in order to identify potential diagnostic resistance markers. METHODOLOGY/PRINCIPAL FINDINGS: We have expressed CYP9J32 in Escherichia coli and show that the enzyme can metabolize the pyrethroids permethrin and deltamethrin. In addition, three other Ae. aegypti P450s (CYP9J24, CYP9J26, CYP9J28 were found capable of pyrethroid metabolism, albeit with lower activity. Both Ae. aegypti and Anopheles gambiae P450s (CYP's 6M2, 6Z2, 6P3 were screened against fluorogenic and luminescent substrates to identify potential diagnostic probes for P450 activity. Luciferin-PPXE was preferentially metabolised by the three major pyrethroid metabolisers (CYP9J32, CYP6M2 and CYP6P3, identifying a potential diagnostic substrate for these P450s. CONCLUSIONS/SIGNIFICANCE: P450s have been identified with the potential to confer pyrethroid resistance in Ae.aegypti. It is recommended that over expression of these enzymes should be monitored as indicators of resistance where pyrethroids are used.
Torres, J B; Rodrigues, A R S; Barros, E M; Santos, D S
Pyrethroid insecticides are widely recommended to control insect defoliators but lack efficacy against most aphid species. Thus, conserving aphid predators such as the lady beetle Eriopis connexa (Germar) is important to pest management in crop ecosystems that require pyrethroid sprays. In a greenhouse, early fourth-instar larvae and 5-day-old adults from susceptible (S) and resistant (R) E. connexa populations were caged on lambda-cyhalothrin-treated cotton plants, after which survival and egg production (for those caged at adult stage) were assessed. In the laboratory, similar groups were subjected to dried residues and topical treatment with one of eight pyrethroids (alpha-cypermethrin, bifenthrin, deltamethrin, esfenvalerate, fenpropathrin, permethrin, zeta-cypermethrin, and lambda-cyhalothrin), the organophosphate methidathion, or water and wetting agent. After caging on treated cotton terminals, 66% of the R-population larvae survived to adulthood, compared with 2% of those from the S-population. At 12 d after caging at adult stage under the same conditions, 64% of the females from the R-population survived and laid eggs, compared with 100% mortality and no oviposition for the S-females. In trials involving dried insecticide residues, gain in survival based on the survival difference (percentage for R-population minus percentage for S-population) across all tested pyrethroids varied from 3 to 63% for larvae and from 3 to 70% for adults. In trials involving topical sprays of the tested pyrethroids, survival differences ranged from 36 to 96% for larvae and from 21 to 82% for adults. Fenpropathrin and bifenthrin were the least and most toxic, respectively. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Full Text Available Abstract Background A mosquito survey was carried out on the island of Likoma in Lake Malawi with a view to collecting baseline data to determine the feasibility of implementing an integrated malaria vector control programme. No vector control interventions are currently being applied on the island apart from the sporadic use of treated and untreated bed nets. Results Large numbers of Anopheles funestus were found resting inside houses. WHO susceptibility tests were carried out on wild caught females and 1-5 day old F-1 female progeny. Wild caught females were tested on deltamethrin (77.8% mortality and bendiocarb (56.4% mortality. Female progeny were tested on deltamethrin (41.4% mortality, permethrin (40.4%, bendiocarb (52.5%, propoxur (7.4%, malathion, fenitrothion, DDT, dieldrin (all 100% and pirimiphos-methyl (98.9%. The malaria parasite rate was 4.9%. A small number of Anopheles arabiensis were also collected. Conclusion This locality is 1,500 km north of the currently known distribution of pyrethroid resistant An. funestus in southern Africa. The susceptibility results mirror those found in southern Mozambique and South African populations, but are markedly different to An. funestus populations in Uganda, indicating that the Malawi resistance has spread from the south.
Bonizzoni, Mariangela; Ochomo, Eric; Dunn, William Augustine; Britton, Monica; Afrane, Yaw; Zhou, Guofa; Hartsel, Joshua; Lee, Ming-Chieh; Xu, Jiabao; Githeko, Andrew; Fass, Joseph; Yan, Guiyun
The extensive use of pyrethroids for control of malaria vectors, driven by their cost, efficacy and safety, has led to widespread resistance. To favor their sustainable use, the World Health Organization (WHO) formulated an insecticide resistance management plan, which includes the identification of the mechanisms of resistance and resistance surveillance. Recognized physiological mechanisms of resistance include target site mutations in the para voltage-gated sodium channel, metabolic detoxification and penetration resistance. Such understanding of resistance mechanisms has allowed the development of resistance monitoring tools, including genotyping of the kdr mutation L1014F/S in the para gene. The sequence-based technique RNA-seq was applied to study changes in the transcriptome of deltamethrin-resistant and -susceptible Anopheles gambiae mosquitoes from the Western Province of Kenya. The resulting gene expression profiles were compared to data in the most recent literature to derive a list of candidate resistance genes. RNA-seq data were analyzed also to identify sequence polymorphisms linked to resistance. A total of five candidate-resistance genes (AGAP04177, AGAP004572, AGAP008840, AGAP007530 and AGAP013036) were identified with altered expression between resistant and susceptible mosquitoes from West and East Africa. A change from G to C at position 36043997 of chromosome 3R resulting in A101G of the sulfotransferase gene AGAP009551 was significantly associated with the resistance phenotype (odds ratio: 5.10). The kdr L1014S mutation was detected at similar frequencies in both phenotypically resistant and susceptible mosquitoes, suggesting it is no longer fully predictive of the resistant phenotype. Overall, these results support the conclusion that resistance to pyrethroids is a complex and evolving phenotype, dependent on multiple gene functions including, but not limited to, metabolic detoxification. Functional convergence among metabolic detoxification
Brooke Basil D
Full Text Available Abstract Background Insecticide resistance can present a major obstacle to malaria control programmes. Following the recent detection of DDT resistance in Anopheles arabiensis in Gokwe, Zimbabwe, the underlying resistance mechanisms in this population were studied. Methods Standard WHO bioassays, using 0.75% permethrin, 4% DDT, 5% malathion, 0.1% bendiocarb and 4% dieldrin were performed on wild-collected adult anopheline mosquitoes and F1 progeny of An. arabiensis reared from wild-caught females. Molecular techniques were used for species identification as well as to identify knockdown resistance (kdr and ace-1 mutations in individual mosquitoes. Biochemical assays were used to determine the relative levels of detoxifying enzyme systems including non-specific esterases, monooxygenases and glutathione-S-transferases as well as to detect the presence of an altered acetylcholine esterase (AChE. Results Anopheles arabiensis was the predominant member of the Anopheles gambiae complex. Of the 436 An. arabiensis females, 0.5% were positive for Plasmodium falciparum infection. WHO diagnostic tests on wild populations showed resistance to the pyrethroid insecticide permethrin at a mean mortality of 47% during February 2006 and a mean mortality of 68.2% in January 2008. DDT resistance (68.4% mean mortality was present in February 2006; however, two years later the mean mortality was 96%. Insecticide susceptibility tests on F1 An. arabiensis families reared from material from two separate collections showed an average mean mortality of 87% (n = 758 after exposure to 4% DDT and 65% (n = 587 after exposure to 0.75% permethrin. Eight families were resistant to both DDT and permethrin. Biochemical analysis of F1 families reared from collections done in 2006 revealed high activity levels of monooxygenase (48.5% of families tested, n = 33, p An. arabiensis colony. Knockdown resistance (kdr and ace-IR mutations were not detected. Conclusion This study confirmed
Sayono, Sayono; Hidayati, Anggie Puspa Nur; Fahri, Sukmal; Sumanto, Didik; Dharmana, Edi; Hadisaputro, Suharyo; Asih, Puji Budi Setia; Syafruddin, Din
The emergence of insecticide resistant Aedes aegypti mosquitoes has hampered dengue control efforts. WHO susceptibility tests, using several pyrethroid compounds, were conducted on Ae. aegypti larvae that were collected and raised to adulthood from Semarang, Surakarta, Kudus and Jepara in Java. The AaNaV gene fragment encompassing kdr polymorphic sites from both susceptible and resistant mosquitoes was amplified, and polymorphisms were associated with the resistant phenotype. The insecticide susceptibility tests demonstrated Ae, aegypti resistance to the pyrethroids, with mortality rates ranging from 1.6%-15.2%. Three non-synonymous polymorphisms (S989P, V1016G and F1534C) and one synonymous polymorphism (codon 982) were detected in the AaNaV gene. Eight AaNaV alleles were observed in specimens from Central Java. Allele 3 (SGF) and allele 7 (PGF) represent the most common alleles found and demonstrated strong associations with resistance to pyrethroids (OR = 2.75, CI: 0.97-7.8 and OR = 7.37, CI: 2.4-22.5, respectively). This is the first report of 8 Ae. aegypti AaNaV alleles, and it indicates the development of resistance in Ae. aegypti in response to pyrethroid insecticide-based selective pressure. These findings strongly suggest the need for an appropriate integrated use of insecticides in the region. The 989P, 1016G and 1534C polymorphisms in the AaNaV gene are potentially valuable molecular markers for pyrethroid insecticide resistance monitoring.
Full Text Available The emergence of insecticide resistant Aedes aegypti mosquitoes has hampered dengue control efforts. WHO susceptibility tests, using several pyrethroid compounds, were conducted on Ae. aegypti larvae that were collected and raised to adulthood from Semarang, Surakarta, Kudus and Jepara in Java. The AaNaV gene fragment encompassing kdr polymorphic sites from both susceptible and resistant mosquitoes was amplified, and polymorphisms were associated with the resistant phenotype. The insecticide susceptibility tests demonstrated Ae, aegypti resistance to the pyrethroids, with mortality rates ranging from 1.6%-15.2%. Three non-synonymous polymorphisms (S989P, V1016G and F1534C and one synonymous polymorphism (codon 982 were detected in the AaNaV gene. Eight AaNaV alleles were observed in specimens from Central Java. Allele 3 (SGF and allele 7 (PGF represent the most common alleles found and demonstrated strong associations with resistance to pyrethroids (OR = 2.75, CI: 0.97-7.8 and OR = 7.37, CI: 2.4-22.5, respectively. This is the first report of 8 Ae. aegypti AaNaV alleles, and it indicates the development of resistance in Ae. aegypti in response to pyrethroid insecticide-based selective pressure. These findings strongly suggest the need for an appropriate integrated use of insecticides in the region. The 989P, 1016G and 1534C polymorphisms in the AaNaV gene are potentially valuable molecular markers for pyrethroid insecticide resistance monitoring.
Pyrethroid insecticides bind to voltage-gated sodium channels (VGSCs) and modify their gating kinetics, thereby disrupting neuronal function. Pyrethroids have also been reported to alter the function of other channel types, including activation of voltage-gated Ca2+ calcium chann...
N'Guessan, Raphael; Ngufor, Corine; Kudom, Andreas A; Boko, Pelagie; Odjo, Abibathou; Malone, David; Rowland, Mark
The effectiveness of insecticide treated nets is under threat across Africa south of the Sahara from the selection of pyrethroid resistance in Anopheles gambiae mosquitoes. To maintain progress against malaria it is necessary to identify alternative residual insecticides for mosquito nets. Mixtures of pyrethroid and insecticides with novel mode of action provide scope for both improved control and management of resistance through concurrent exposure to unrelated insecticides. The pyrrole chlorfenapyr and the pyrethroid alphacypermethrin were tested individually and as a mixture on mosquito nets in an experimental hut trial in southern Benin against pyrethroid resistant An gambiae and Culex quinquefasciatus mosquitoes. The nets were deliberately holed to simulate the effect of wear and tear. The nets treated with the mixture of chlorfenapyr 200 mg/m² and alphacypermethrin 25 mg/m² killed a proportion of An gambiae (77%, 95%CI: 66-86%) significantly greater than nets treated with alphacypermethrin 25 mg/m(2) (30%, 95%CI: 21-41%) but not significantly different from nets treated with chlorfenapyr 200 mg/m² (69%, 95%CI: 57-78%). The nets treated with the mixtures procured personal protection against An gambiae biting(58-62%) by a greater margin than the alphacypermethrin treated net (39%), whereas the chlorfenapyr treated net was not protective. A similar trend in mortality and blood feeding inhibition between treatments was observed in Cx quinquefasciatus to that seen in An. gambiae, although the effects were lower. A mixture of alphacypermethrin with chlorfenapyr applied at 100 mg/m² had an effect similar to the mixture with chlorfenapyr at 200 mg/m². The effectiveness of ITNs against pyrethroid resistant mosquitoes was restored by the mixture: the alphacypermethrin component reduced human-vector contact while the chlorfenapyr controlled pyrethroid-resistant mosquitoes. The complementary action of these unrelated insecticides demonstrates that the combination on
Intirach, J; Junkum, A; Lumjuan, N; Chaithong, U; Jitpakdi, A; Riyong, D; Wannasan, A; Champakaew, D; Muangmoon, R; Chansang, A; Pitasawat, B
The increasing and widespread resistance to conventional synthetic insecticides in vector populations has underscored the urgent need to establish alternatives in the mosquito management system. This study was carried out with the aim to investigate the antimosquito property, larvicidal and adulticidal potential, of plant products against both the pyrethroid-susceptible and resistant strains of Aedes aegypti. Seventeen plant products, including essential oils and ethanolic extracts, were obtained by steam distillation and extraction with 95 % ethanol, respectively. Their larvicidal activity was screened, using World Health Organization (WHO) procedures against A. aegypti, Muang Chiang Mai-susceptible (MCM-S) strain. The most effective product was a candidate for investigating larvicidal and adulticidal potential against three laboratory strains of A. aegypti, comprising MCM-S, Pang Mai Dang-resistant (PMD-R), and Upakut-resistant (UPK-R). Potential toxicity of the plant candidate was compared with that of synthetic temephos, permethrin, and deltamethrin. Chemical constituents of the most effective plant product also were analyzed by gas chromatography-mass spectrometry (GC-MS). Results obtained from the preliminary screening revealed the varying larvicidal efficacy of plant-derived products against MCM-S A. aegypti, with mortality ranging from 0 to 100 %. The larvicidal activity of seven effective plant products was found to be dose dependent, with the highest efficacy established from Petroselinum crispum fruit oil, followed by oils of Foeniculum vulgare, Myristica fragrans, Limnophila aromatica, Piper sarmentosum, Curcuma longa, and M. fragrans ethanolic extract (LC50 values of 43.22, 44.84, 47.42, 47.94, 49.19, 65.51, and 75.45 ppm, respectively). Essential oil of P. crispum was then investigated further and proved to be a promising larvicide and adulticide against all strains of A. aegypti. The pyrethroid-resistant strains of both PMD-R and UPK-R A. aegypti
Lumjuan, Nongkran; Rajatileka, Shavanthi; Changsom, Donch; Wicheer, Jureeporn; Leelapat, Posri; Prapanthadara, La-aied; Somboon, Pradya; Lycett, Gareth; Ranson, Hilary
The Epsilon glutathione transferase (GST) class in the dengue vector Aedes aegypti consists of eight sequentially arranged genes spanning 53,645 bp on super contig 1.291, which maps to chromosome 2. One Epsilon GST, GSTE2, has previously been implicated in conferring resistance to DDT. The amino acid sequence of GSTE2 in an insecticide susceptible and a DDT resistant strain differs at five residues two of which occur in the putative DDT binding site. Characterization of the respective recombinant enzymes revealed that both variants have comparable DDT dehydrochlorinase activity although the isoform from the resistant strain has higher affinity for the insecticide. GSTe2 and two additional Epsilon GST genes, GSTe5 and GSTe7, are expressed at elevated levels in the resistant population and the recombinant homodimer GSTE5-5 also exhibits low levels of DDT dehydrochlorinase activity. Partial silencing of either GSTe7 or GSTe2 by RNA interference resulted in an increased susceptibility to the pyrethroid, deltamethrin suggesting that these GST enzymes may also play a role in resistance to pyrethroid insecticides.
Konan, K G; Koné, A B; Konan, Y L; Fofana, D; Konan, K L; Diallo, A; Ziogba, J C; Touré, M; Kouassi, K P; Doannio, J M C
An assessment of the sensitivity of Anopheles gambiae s.l.to three pyrethroids (alphacypermethrin, permethrin, deltamethrin) and DDT has been carried out with a laboratory strain (Kisumu reference sensitive strain) and a wild strain (Tiassalékro strain) using larvae from an irrigated rice-growing area of Tiassalékro, located in the southern forest of Ivory Coast. The sensitivity tests were performed according to the standard WHO cylinder tests with adult female A. gambiae s.l. aged 2 to 4 days. The results showed that the strain of Tiassalékro is resistant to the three tested pyrethroids and DDT. The molecular forms M and S were identified, with a predominance of M form. The resistance mechanism involved is the Kdr mutation. In this region, control measures against malaria vectors by using bed nets impregnated with these insecticides or household sprays could be compromised.
Jensen, Karl-Martin Vagn; Fomsgaard, Inge S.; Kilpinen, Ole Østerlund;
A number of different methods are tested to elucidate the accumulation of synthetic pyrethroids in private homes. When the target pest is resistant, there is a potential risk that persistent synthetic pyrethroids accumulate because of repeated treatments. The highest residue found was 8260 µg...
Grubor, Vladimir D; Heckel, David G
The AN02 strain of Helicoverpa armigera from eastern Australia exhibits 50-fold, PBO-suppressible resistance to the pyrethroid insecticide fenvalerate. The semidominant resistance gene RFen1 was previously mapped to AFLP Linkage Group 13. In evaluating the cytochrome P450 genes CYP6B7, CYP6B6, and CYP6B2 as candidates for RFen1, we found that they occur in a tandem array in the genome, next to the gene encoding the para-type sodium channel; the target of pyrethroid insecticides. We mapped these genes to AFLP Linkage Group 14, thus rejecting mutations within the P450 cluster or para as candidates for RFen1. RFen1 genotypes produced slightly different mRNA levels of the three P450s, but the differences were too small to convincingly account for resistance. We conclude that even if one or more of these P450s metabolize fenvalerate, they are unlikely to be responsible for the resistance in AN02.
Faucon, Frederic; Gaude, Thierry; Dusfour, Isabelle; Navratil, Vincent; Corbel, Vincent; Juntarajumnong, Waraporn; Girod, Romain; Poupardin, Rodolphe; Boyer, Frederic; Reynaud, Stephane; David, Jean-Philippe
The capacity of Aedes mosquitoes to resist chemical insecticides threatens the control of major arbovirus diseases worldwide. Until alternative control tools are widely deployed, monitoring insecticide resistance levels and identifying resistance mechanisms in field mosquito populations is crucial for implementing appropriate management strategies. Metabolic resistance to pyrethroids is common in Aedes aegypti but the monitoring of the dynamics of resistant alleles is impeded by the lack of robust genomic markers. In an attempt to identify the genomic bases of metabolic resistance to deltamethrin, multiple resistant and susceptible populations originating from various continents were compared using both RNA-seq and a targeted DNA-seq approach focused on the upstream regions of detoxification genes. Multiple detoxification enzymes were over transcribed in resistant populations, frequently associated with an increase in their gene copy number. Targeted sequencing identified potential promoter variations associated with their over transcription. Non-synonymous variations affecting detoxification enzymes were also identified in resistant populations. This study not only confirmed the role of gene copy number variations as a frequent cause of the over expression of detoxification enzymes associated with insecticide resistance in Aedes aegypti but also identified novel genomic resistance markers potentially associated with their cis-regulation and modifications of their protein structure conformation. As for gene transcription data, polymorphism patterns were frequently conserved within regions but differed among continents confirming the selection of different resistance factors worldwide. Overall, this study paves the way of the identification of a comprehensive set of genomic markers for monitoring the spatio-temporal dynamics of the variety of insecticide resistance mechanisms in Aedes aegypti.
Full Text Available Pyrethroid insecticides, especially permethrin and deltamethrin, have been used extensively worldwide for mosquito control. However, insecticide resistance can spread through a population very rapidly under strong selection pressure from insecticide use. The upregulation of aldehyde dehydrogenase (ALDH has been reported upon pyrethroid treatment. In Aedes aegypti, the increase in ALDH activity against the hydrolytic product of pyrethroid has been observed in DDT/permethrin-resistant strains. The objective of this study was to identify the role of individual ALDHs involved in pyrethroid metabolism.Three ALDHs were identified; two of these, ALDH9948 and ALDH14080, were upregulated in terms of both mRNA and protein levels in a DDT/pyrethroid-resistant strain of Ae. aegypti. Recombinant ALDH9948 and ALDH14080 exhibited oxidase activities to catalyse the oxidation of a permethrin intermediate, phenoxybenzyl aldehyde (PBald, to phenoxybenzoic acid (PBacid.ALDHs have been identified in association with permethrin resistance in Ae. aegypti. Characterisation of recombinant ALDHs confirmed the role of this protein in pyrethroid metabolism. Understanding the biochemical and molecular mechanisms of pyrethroid resistance provides information for improving vector control strategies.
Full Text Available Abstract Background An important advantage of pyrethroid-treated nets over untreated nets is that once nets become worn or holed a pyrethroid treatment will normally restore protection. The capacity of pyrethroids to kill or irritate any mosquito that comes into contact with the net and prevent penetration of holes or feeding through the sides are the main reasons why treated nets continue to provide protection despite their condition deteriorating over time. Pyrethroid resistance is a growing problem among Anopheline and Culicine mosquitoes in many parts of Africa. When mosquitoes become resistant the capacity of treated nets to provide protection might be diminished, particularly when holed. An experimental hut trial against pyrethroid-resistant Culex quinquefasciatus was therefore undertaken in southern Benin using a series of intact and holed nets, both untreated and treated, to assess any loss of protection as nets deteriorate with use and time. Results There was loss of protection when untreated nets became holed; the proportion of mosquitoes blood feeding increased from 36.2% when nets were intact to between 59.7% and 68.5% when nets were holed to differing extents. The proportion of mosquitoes blood feeding when treated nets were intact was 29.4% which increased to 43.6–57.4% when nets were holed. The greater the number of holes the greater the loss of protection regardless of whether nets were untreated or treated. Mosquito mortality in huts with untreated nets was 12.9–13.6%; treatment induced mortality was less than 12%. The exiting rate of mosquitoes into the verandas was higher in huts with intact nets. Conclusion As nets deteriorate with use and become increasingly holed the capacity of pyrethroid treatments to restore protection is greatly diminished against resistant Culex quinquefasciatus mosquitoes.
Francesca Guaracyaba Garcia Chapadense
Full Text Available ABSTRACTINTRODUCTION:The mosquito Aedes aegypti has evolved resistance to pyrethroid insecticides. The present study evaluated Ae. aegypti from Goiânia for the resistant phenotype and for mutations associated with resistance.METHODS:Insecticide dose-response bioassays were conducted on mosquitoes descended from field-collected eggs, and polymerase chain reaction (PCR was used to genotype 90 individuals at sites implicated in pyrethroid resistance.RESULTS:All mosquito populations displayed high levels of resistance to deltamethrin, as well as high frequencies of the 1016Ile kdr and 1534Cys kdrmutations.CONCLUSIONS:Aedes aegypti populations in the Goiânia area are highly resistant to deltamethrin, presumably due to high frequencies of kdr(knockdown-resistance mutations.
Sayono, Sayono; Hidayati, Anggie Puspa Nur; Fahri, Sukmal; Sumanto, Didik; Dharmana, Edi; Hadisaputro, Suharyo; Asih, Puji Budi Setia; Syafruddin, Din
The emergence of insecticide resistant Aedes aegypti mosquitoes has hampered dengue control efforts. WHO susceptibility tests, using several pyrethroid compounds, were conducted on Ae. aegypti larvae that were collected and raised to adulthood from Semarang, Surakarta, Kudus and Jepara in Java. The AaNaV gene fragment encompassing kdr polymorphic sites from both susceptible and resistant mosquitoes was amplified, and polymorphisms were associated with the resistant phenotype. The insecticide susceptibility tests demonstrated Ae, aegypti resistance to the pyrethroids, with mortality rates ranging from 1.6%–15.2%. Three non-synonymous polymorphisms (S989P, V1016G and F1534C) and one synonymous polymorphism (codon 982) were detected in the AaNaV gene. Eight AaNaV alleles were observed in specimens from Central Java. Allele 3 (SGF) and allele 7 (PGF) represent the most common alleles found and demonstrated strong associations with resistance to pyrethroids (OR = 2.75, CI: 0.97–7.8 and OR = 7.37, CI: 2.4–22.5, respectively). This is the first report of 8 Ae. aegypti AaNaV alleles, and it indicates the development of resistance in Ae. aegypti in response to pyrethroid insecticide-based selective pressure. These findings strongly suggest the need for an appropriate integrated use of insecticides in the region. The 989P, 1016G and 1534C polymorphisms in the AaNaV gene are potentially valuable molecular markers for pyrethroid insecticide resistance monitoring. PMID:26939002
Carvajal, Guillermo; Picollo, María Inés; Toloza, Ariel Ceferino
The prevention of Chagas disease is based primarily on the chemical control of Triatoma infestans (Klug) using pyrethroid insecticides. However, high resistance levels, correlated with control failures, have been detected in Argentina and Bolivia. A previous study at our laboratory found that imidacloprid could serve as an alternative to pyrethroid insecticides. We studied the delayed toxicity of imidacloprid and the influence of the blood feeding condition of the insect on the toxicity of this insecticide; we also studied the effectiveness of various commercial imidacloprid formulations against a pyrethroid-resistant T. infestans population from the Gran Chaco ecoregion. Variations in the toxic effects of imidacloprid were not observed up to 72 h after exposure and were not found to depend on the blood feeding condition of susceptible and resistant individuals. Of the three different studied formulations of imidacloprid on glass and filter paper, only the spot-on formulation was effective. This formulation was applied to pigeons at doses of 1, 5, 20 and 40 mg/bird. The nymphs that fed on pigeons treated with 20 mg or 40 mg of the formulation showed a higher mortality rate than the control group one day and seven days post-treatment (p imidacloprid was effective against pyrethroid-resistant T. infestans populations at the laboratory level.
Full Text Available The prevention of Chagas disease is based primarily on the chemical control of Triatoma infestans (Klug using pyrethroid insecticides. However, high resistance levels, correlated with control failures, have been detected in Argentina and Bolivia. A previous study at our laboratory found that imidacloprid could serve as an alternative to pyrethroid insecticides. We studied the delayed toxicity of imidacloprid and the influence of the blood feeding condition of the insect on the toxicity of this insecticide; we also studied the effectiveness of various commercial imidacloprid formulations against a pyrethroid-resistant T. infestans population from the Gran Chaco ecoregion. Variations in the toxic effects of imidacloprid were not observed up to 72 h after exposure and were not found to depend on the blood feeding condition of susceptible and resistant individuals. Of the three different studied formulations of imidacloprid on glass and filter paper, only the spot-on formulation was effective. This formulation was applied to pigeons at doses of 1, 5, 20 and 40 mg/bird. The nymphs that fed on pigeons treated with 20 mg or 40 mg of the formulation showed a higher mortality rate than the control group one day and seven days post-treatment (p < 0.01. A spot-on formulation of imidacloprid was effective against pyrethroid-resistant T. infestans populations at the laboratory level.
Full Text Available BACKGROUND: Chagas' disease is an important public health concern in Latin America. Despite intensive vector control efforts using pyrethroid insecticides, the elimination of Triatoma infestans has failed in the Gran Chaco, an ecoregion that extends over Argentina, Paraguay, Bolivia and Brazil. The voltage-gated sodium channel is the target site of pyrethroid insecticides. Point mutations in domain II region of the channel have been implicated in pyrethroid resistance of several insect species. METHODS AND FINDINGS: In the present paper, we identify L925I, a new pyrethroid resistance-conferring mutation in T. infestans. This mutation has been found only in hemipterans. In T. infestans, L925I mutation occurs in a resistant population from the Gran Chaco region and is associated with inefficiency in the control campaigns. We also describe a method to detect L925I mutation in individuals from the field. CONCLUSIONS AND SIGNIFICANCE: The findings have important implications in the implementation of strategies for resistance management and in the rational design of campaigns for the control of Chagas' disease transmission.
Gustavo A. Sabatini
Full Text Available To investigate the kdr (knockdown resistance resistance-associated gene mutation and determine its frequency in pyrethroid-resistant horn fly (Haematobia irritans populations, a total of 1,804 horn flies of 37 different populations from all Brazilian regions (North, Northeast, Central-West, Southeast, and South were molecular screened through polymerase chain reaction (PCR. The kdr gene was not detected in 87.08% of the flies. However, the gene was amplified in 12.92% of the flies, of which 11.70% were resistant heterozygous and 1.22% were resistant homozygous. Deviation from Hardy-Weinberg equilibrium (HWE was found only in 1 ranch with an excess of heterozygous. When populations were grouped by region, three metapopulations showed significant deviations of HWE (Central-West population, South population and Southeast population. This indicates that populations are isolated one from another and kdr occurrence seems to be an independent effect probably reflecting the insecticide strategy used by each ranch. Although resistance to pyrethroids is disseminated throughout Brazil, only 48% of resistant populations had kdr flies, and the frequency of kdr individuals in each of these resistant populations was quite low. But this study shows that, with the apparent exception of the Northeast region, the kdr mechanism associated with pyrethroid resistance occurs all over Brazil.Com o objetivo de verificar a ocorrência e determinar a frequência da mutação kdr (knock down resistance em populações de Haematobia irritans (mosca-dos-chifres resistentes aos piretróides, foram analisados 1.804 indivíduos de 37 populações de todas as Regiões do Brasil. Com exceção da Região Nordeste, o kdr (knock down resistance gene foi encontrado em populações de todas as regiões. A mutação não foi detectada em 87,08% dos indivíduos. Entretanto, o gene foi amplificado de 12,92% das moscas, das quais 11,70% se mostraram heterozigotas resistentes e 1
Sayono Sayono; Anggie Puspa Nur Hidayati; Sukmal Fahri; Didik Sumanto; Edi Dharmana; Suharyo Hadisaputro; Puji Budi Setia Asih; Din Syafruddin
The emergence of insecticide resistant Aedes aegypti mosquitoes has hampered dengue control efforts. WHO susceptibility tests, using several pyrethroid compounds, were conducted on Ae. aegypti larvae that were collected and raised to adulthood from Semarang, Surakarta, Kudus and Jepara in Java. The AaNa V gene fragment encompassing kdr polymorphic sites from both susceptible and resistant mosquitoes was amplified, and polymorphisms were associated with the resistant phenotype. The insecticide...
Full Text Available Abstract Background Neither indoor residual spraying (IRS nor long-lasting insecticidal nets (LLINs are able to fully interrupt transmission in holoendemic Africa as single interventions. The combining of IRS and LLINs presents an opportunity for improved control and management of pyrethroid resistance through the simultaneous presentation of unrelated insecticides. Method Chlorfenapyr IRS and a pyrethroid-impregnated polyester LLIN (WHO approved were tested separately and together in experimental huts in southern Benin against pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus. The bed nets were deliberately holed with either six or 80 holes to examine the effect of increasing wear and tear on protectiveness. Anopheles gambiae were genotyped for the kdr gene to assess the combination's potential to prevent the selection of pyrethroid resistance. Results The frequency of kdr was 84%. The overall mortality rates of An. gambiae were 37% and 49% with the six-hole and 80-hole LLINs, respectively, and reached 57% with chlorfenapyr IRS. Overall mortality rates were significantly higher with the combination treatments (82-83% than with the LLIN or IRS individual treatments. Blood feeding (mosquito biting rates were lowest with the 6-hole LLIN (12%, intermediate with the 80-hole LLIN (32% and highest with untreated nets (56% with the 6-hole and 54% with the 80-hole nets. Blood feeding (biting rates and repellency of mosquitoes with the combination of LLIN and chlorfenapyr IRS showed significant improvement compared to the IRS treatment but did not differ from the LLIN treatments indicating that the LLINs were the primary agents of personal protection. The combination killed significantly higher proportions of Cx. quinquefasciatus (51%, 41% than the LLIN (15%, 13% or IRS (32% treatments. Conclusion The chlorfenapyr IRS component was largely responsible for controlling pyrethroid-resistant mosquitoes and the LLIN component was largely
Ngufor, Corine; N'Guessan, Raphael; Boko, Pelagie; Odjo, Abibatou; Vigninou, Estelle; Asidi, Alex; Akogbeto, Martin; Rowland, Mark
Neither indoor residual spraying (IRS) nor long-lasting insecticidal nets (LLINs) are able to fully interrupt transmission in holoendemic Africa as single interventions. The combining of IRS and LLINs presents an opportunity for improved control and management of pyrethroid resistance through the simultaneous presentation of unrelated insecticides. Chlorfenapyr IRS and a pyrethroid-impregnated polyester LLIN (WHO approved) were tested separately and together in experimental huts in southern Benin against pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus. The bed nets were deliberately holed with either six or 80 holes to examine the effect of increasing wear and tear on protectiveness. Anopheles gambiae were genotyped for the kdr gene to assess the combination's potential to prevent the selection of pyrethroid resistance. The frequency of kdr was 84%. The overall mortality rates of An. gambiae were 37% and 49% with the six-hole and 80-hole LLINs, respectively, and reached 57% with chlorfenapyr IRS. Overall mortality rates were significantly higher with the combination treatments (82-83%) than with the LLIN or IRS individual treatments. Blood feeding (mosquito biting) rates were lowest with the 6-hole LLIN (12%), intermediate with the 80-hole LLIN (32%) and highest with untreated nets (56% with the 6-hole and 54% with the 80-hole nets). Blood feeding (biting) rates and repellency of mosquitoes with the combination of LLIN and chlorfenapyr IRS showed significant improvement compared to the IRS treatment but did not differ from the LLIN treatments indicating that the LLINs were the primary agents of personal protection. The combination killed significantly higher proportions of Cx. quinquefasciatus (51%, 41%) than the LLIN (15%, 13%) or IRS (32%) treatments. The chlorfenapyr IRS component was largely responsible for controlling pyrethroid-resistant mosquitoes and the LLIN component was largely responsible for blood feeding inhibition and personal
Full Text Available BACKGROUND: The effectiveness of insecticide treated nets is under threat across Africa south of the Sahara from the selection of pyrethroid resistance in Anopheles gambiae mosquitoes. To maintain progress against malaria it is necessary to identify alternative residual insecticides for mosquito nets. Mixtures of pyrethroid and insecticides with novel mode of action provide scope for both improved control and management of resistance through concurrent exposure to unrelated insecticides. METHODS: The pyrrole chlorfenapyr and the pyrethroid alphacypermethrin were tested individually and as a mixture on mosquito nets in an experimental hut trial in southern Benin against pyrethroid resistant An gambiae and Culex quinquefasciatus mosquitoes. The nets were deliberately holed to simulate the effect of wear and tear. RESULTS: The nets treated with the mixture of chlorfenapyr 200 mg/m² and alphacypermethrin 25 mg/m² killed a proportion of An gambiae (77%, 95%CI: 66-86% significantly greater than nets treated with alphacypermethrin 25 mg/m(2 (30%, 95%CI: 21-41% but not significantly different from nets treated with chlorfenapyr 200 mg/m² (69%, 95%CI: 57-78%. The nets treated with the mixtures procured personal protection against An gambiae biting(58-62% by a greater margin than the alphacypermethrin treated net (39%, whereas the chlorfenapyr treated net was not protective. A similar trend in mortality and blood feeding inhibition between treatments was observed in Cx quinquefasciatus to that seen in An. gambiae, although the effects were lower. A mixture of alphacypermethrin with chlorfenapyr applied at 100 mg/m² had an effect similar to the mixture with chlorfenapyr at 200 mg/m². CONCLUSION: The effectiveness of ITNs against pyrethroid resistant mosquitoes was restored by the mixture: the alphacypermethrin component reduced human-vector contact while the chlorfenapyr controlled pyrethroid-resistant mosquitoes. The complementary action of these
Stewart, Zachary P; Oxborough, Richard M; Tungu, Patrick K; Kirby, Matthew J; Rowland, Mark W; Irish, Seth R
Attractive toxic sugar bait (ATSB) sprayed onto vegetation has been successful in controlling Anopheles mosquitoes outdoors. Indoor application of ATSB has yet to be explored. The purpose of this study was to determine whether ATSB stations positioned indoors have the potential to kill host-seeking mosquitoes and constitute a new approach to control of mosquito-borne diseases. Insecticides were mixed with dyed sugar solution and tested as toxic baits against Anopheles arabiensis, An. Gambiae s.s. and Culex quinquefasciatus in feeding bioassay tests to identify suitable attractant-insecticide combinations. The most promising ATSB candidates were then trialed in experimental huts in Moshi, Tanzania. ATSB stations were hung in huts next to untreated mosquito nets occupied by human volunteers. The proportions of mosquitoes killed in huts with ATSB treatments relative to huts with non-insecticide control treatments huts were recorded, noting evidence of dye in mosquito abdomens. In feeding bioassays, chlorfenapyr 0.5% v/v, boric acid 2% w/v, and tolfenpyrad 1% v/v, mixed in a guava juice-based bait, each killed more than 90% of pyrethroid-susceptible An. Gambiae s.s. and pyrethroid-resistant An. arabiensis and Cx. quinquefasciatus. In the hut trial, mortality rates of the three ATSB treatments ranged from 41-48% against An. arabiensis and 36-43% against Cx. quinquefasciatus and all were significantly greater than the control mortalities: 18% for An. arabiensis, 7% for Cx. quinquefasciatus (pmosquito nets for controlling mosquitoes. Indoor ATSB constitute a novel application method for insecticide classes that act as stomach poisons and have not hitherto been exploited for mosquito control. Combined with LLIN, indoor use of ATSB has the potential to serve as a strategy for managing insecticide resistance.
Singh, Nirbhay Kumar; Jyoti; Vemu, Bhaskar; Singh, Harkirat; Prerna, Mranalini; Daundkar, Prashant S; Sharma, S K; Dumka, V K
Larval packet test was used for detection of resistance status against cypermethrin and deltamethrin, the most commonly used synthetic pyrethroids in Rhipicephalus (Boophilus) microplus collected from Faridkot district, Punjab (India). The slope of mortality, lethal concentration for 50 % (LC50) and resistance levels were determined from the regression graphs of probit mortality of ticks plotted against log values of increasing concentrations of cypermethrin and deltamethrin. Results indicated presence of resistance of levels I and II against cypermethrin (resistance factor (RF) = 2.82) and deltamethrin (RF = 8.44), respectively. Adult immersion test was used to assess the acaricidal activity of aqueous (MLAq), ethanol (MLE), chloroform (MLC), acetone (MLA) and hexane (MLH) extracts of leaves of Murraya koenigii against these synthetic pyrethroid (SP)-resistant engorged adult females of R. (B.) microplus by determination of per cent adult mortality, reproductive index (RI), per cent inhibition of oviposition (%IO) and hatching rate. The per cent mortality caused by various extracts at concentrations ranging from 0.625 to 10.0% varied from 0.0 to 100.0% with maximum per cent mortality of 10.0, 100.0, 70.0, 40.0 and 10.0 recorded against MLAq, MLE, MLC, MLA and MLH, respectively. Among all extracts, the highest acaricidal property against SP-resistant R. (B.) microplus was exhibited by the MLE as it showed the minimum LC50 [95% confidence limit (CL)] values of 2.97% (2.82-3.12%), followed by MLC as 10.26% (8.84-11.91 %) and MLA as 18.22% (16.18-20.52%). The average egg mass weight recorded in live ticks treated with various concentrations of different extracts was lower than the respective control group ticks and was significantly (p < 0.01) lower in ticks treated with MLH extract. However, no significant effect on hatchability of eggs of treated groups when compared to control was recorded. A significant (p < 0.05) decrease in the RI was recorded in
Ma, Kai; Li, Xixi; Hu, Hongxia; Zhou, Dan; Sun, Yan; Ma, Lei; Zhu, Changliang; Shen, Bo
The wide use of pyrethroids has resulted in the emergence and spread of resistance in mosquito populations, which represent a major obstacle in the struggle against vector-borne diseases. Resistance to pyrethroids is a complex genetic phenomenon attributed by polygenetic inheritance. We previously have sequenced and analyzed the miRNA profiles of Culex pipiens pallens. MiR-92a was found to be overexpressed in a deltamethrin-resistant (DR) strain. The association of miR-92a with pyrethroid-resistance was investigated by quantitative reverse transcription PCR (qRT-PCR). Expression levels of miR-92a were 2.72-fold higher in the DR strain than in the deltamethrin-susceptible (DS) strain. Bioinformatic analysis suggested that CpCPR4, a mosquito cuticle gene, is the target of miR-92a. Dual luciferase reporter assays further confirmed that CpCPR4 is modulated by miR-92a through binding to a specific target site in the 3' untranslated region (3' UTR). Microinjection of the miR-92a inhibitor upregulated CpCPR4 expression levels, leading to an increase in the susceptibility of the DR strain in the Centers for Disease Control and Prevention (CDC) bottle bioassay (a surveillance tool for detecting resistance to insecticides in vector populations). Taken together, our findings indicate that miR-92a regulates pyrethroid-resistance through its interaction with CpCPR4. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Godara, R; Katoch, R; Yadav, A; Ahanger, R R; Bhutyal, A D S; Verma, P K; Katoch, M; Dutta, S; Nisa, F; Singh, N K
Detection of resistance levels against deltamethrin and cypermethrin in Rhipicephalus (Boophilus) microplus collected from Jammu (India) was carried out using larval packet test (LPT). The results showed the presence of resistance level II and I against deltamethrin and cypermethrin, respectively. Adult immersion test (AIT) and LPT were used to evaluate the in vitro efficacy of ethanolic and aqueous floral extracts of Calendula officinalis against synthetic pyrethroid resistant adults and larvae of R. (B.) microplus. Four concentrations (1.25, 2.5, 5 and 10 %) of each extract with four replications for each concentration were used in both the bioassays. A concentration dependent mortality was observed and it was more marked with ethanolic extract. In AIT, the LC50 values for ethanolic and aqueous extracts were calculated as 9.9 and 12.9 %, respectively. The egg weight of the live ticks treated with different concentrations of the ethanolic and aqueous extracts was significantly lower than that of control ticks; consequently, the reproductive index and the percent inhibition of oviposition values of the treated ticks were reduced. The complete inhibition of hatching was recorded at 10 % of ethanolic extract. The 10 % extracts caused 100 % mortality of larvae after 24 h. In LPT, the LC50 values for ethanolic and aqueous extracts were determined to be 2.6 and 3.2 %, respectively. It can be concluded that the ethanolic extract of C. officinalis had better acaricidal properties against adults and larvae of R. (B.) microplus than the aqueous extract.
Full Text Available BACKGROUND: Single amino acid substitutions in the voltage-gated sodium channel associated with pyrethroid resistance constitute one of the main causative factors of knockdown resistance in insects. The kdr gene has been observed in several mosquito species; however, point mutations in the para gene of Aedes aegypti populations in Myanmar have not been fully characterized. The aim of the present study was to determine the types and frequencies of mutations in the para gene of Aedes aegypti collected from used tires in Yangon City, Myanmar. METHODOLOGY/PRINCIPAL FINDINGS: We determined high pyrethroid resistance in Aedes aegypti larvae at all collection sites in Yangon City, by using a simplified knockdown bioassay. We showed that V1016G and S989P mutations were widely distributed, with high frequencies (84.4% and 78.8%, respectively. By contrast, we were unable to detect I1011M (or I1011V or L1014F mutations. F1534C mutations were also widely distributed, but with a lower frequency than the V1016G mutation (21.2%. High percentage of co-occurrence of the homozygous V1016G/S989P mutations was detected (65.7%. Additionally, co-occurrence of homozygous V1016G/F1534C mutations (2.9% and homozygous V1016G/F1534C/S989P mutations (0.98% were detected in the present study. CONCLUSIONS/SIGNIFICANCE: Pyrethroid insecticides were first used for malaria control in 1992, and have since been constantly used in Myanmar. This intensive use may explain the strong selection pressure toward Aedes aegypti, because this mosquito is generally a domestic and endophagic species with a preference for indoor breeding. Extensive use of DDT for malaria control before the use of this chemical was banned may also explain the development of pyrethroid resistance in Aedes aegypti.
Kawada, Hitoshi; Oo, Sai Zaw Min; Thaung, Sein; Kawashima, Emiko; Maung, Yan Naung Maung; Thu, Hlaing Myat; Thant, Kyaw Zin; Minakawa, Noboru
Single amino acid substitutions in the voltage-gated sodium channel associated with pyrethroid resistance constitute one of the main causative factors of knockdown resistance in insects. The kdr gene has been observed in several mosquito species; however, point mutations in the para gene of Aedes aegypti populations in Myanmar have not been fully characterized. The aim of the present study was to determine the types and frequencies of mutations in the para gene of Aedes aegypti collected from used tires in Yangon City, Myanmar. We determined high pyrethroid resistance in Aedes aegypti larvae at all collection sites in Yangon City, by using a simplified knockdown bioassay. We showed that V1016G and S989P mutations were widely distributed, with high frequencies (84.4% and 78.8%, respectively). By contrast, we were unable to detect I1011M (or I1011V) or L1014F mutations. F1534C mutations were also widely distributed, but with a lower frequency than the V1016G mutation (21.2%). High percentage of co-occurrence of the homozygous V1016G/S989P mutations was detected (65.7%). Additionally, co-occurrence of homozygous V1016G/F1534C mutations (2.9%) and homozygous V1016G/F1534C/S989P mutations (0.98%) were detected in the present study. Pyrethroid insecticides were first used for malaria control in 1992, and have since been constantly used in Myanmar. This intensive use may explain the strong selection pressure toward Aedes aegypti, because this mosquito is generally a domestic and endophagic species with a preference for indoor breeding. Extensive use of DDT for malaria control before the use of this chemical was banned may also explain the development of pyrethroid resistance in Aedes aegypti.
Chourasia, Mehul Kumar; Kamaraju, Raghavendra; Kleinschmidt, Immo; Bhatt, Rajendra M; Swain, Dipak Kumar; Knox, Tessa Bellamy; Valecha, Neena
Subclinical (asymptomatic) cases of malaria could be a major barrier to the success of malaria elimination programs. This study has evaluated the impact of long-lasting insecticidal nets (LLINs) on the prevalence of subclinical malaria in the presence of pyrethroid resistance in the main malaria vector Anopheles culicifacies on malaria transmission among a cohort of children in villages of the Keshkal sub-district in Chhattisgarh state. A cohort of 6582 children ages less than 14 years was enrolled from 80 study clusters. Post monsoon survey was carried out at baseline before LLIN distribution, and 5862 children were followed up in the subsequent year. Study outcomes included assessment of subclinical malarial infections and use of LLINs among the study cohort in the presence of varied levels of pyrethroid resistance. In the baseline survey, the proportion of subclinical malaria was 6·1%. LLIN use during the previous night was 94·8%. Overall, prevalence of subclinical malaria was significantly reduced to 1% (pmalaria (OR: 0·25, 95% CI=0·12-0·52, pmalaria (OR: 0·25, 95% CI=0·11-0·58, p=0·001) despite the presence of pyrethroid resistance in the study area. In this low transmission area, sleeping under LLINs significantly reduced the burden of malaria among children. In the presence of pyrethroid resistant malaria vector, a high LLIN use of 94·5% was observed to have significantly brought down the proportion of subclinical malaria among the cohort children. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Full Text Available Abstract Background Combination mosquito nets incorporating two unrelated insecticides or insecticide plus synergist are designed to control insecticide resistant mosquitoes. PermaNet 3.0 is a long-lasting combination net incorporating deltamethrin on the side panels and a mixture of deltamethrin and synergist piperonyl butoxide (PBO on the top panel. PBO is an inhibitor of mixed function oxidases implicated in pyrethroid resistance. Method An experimental hut trial comparing PermaNet 3.0, PermaNet 2.0 and a conventional deltamethrin-treated net was conducted in NE Tanzania using standard WHOPES procedures. The PermaNet arms included unwashed nets and nets washed 20 times. PermaNet 2.0 is a long-lasting insecticidal net incorporating deltamethrin as a single active. Results Against pyrethroid susceptible Anopheles gambiae the unwashed PermaNet 3.0 showed no difference to unwashed PermaNet 2.0 in terms of mortality (95% killed, but showed differences in blood-feeding rate (3% blood-fed with PermaNet 3.0 versus 10% with PermaNet 2.0. After 20 washes the two products showed no difference in feeding rate (10% with 3.0 and 9% with 2.0 but showed small differences in mortality (95% with 3.0 and 87% with 2.0. Against pyrethroid resistant Culex quinquefasciatus, mediated by elevated oxidase and kdr mechanisms, the unwashed PermaNet 3.0 killed 48% and PermaNet 2.0 killed 32% but after 20 washes there was no significant difference in mortality between the two products (32% killed by 3.0 and 30% by 2.0. For protecting against Culex PermaNet 3.0 showed no difference to PermaNet 2.0 when either unwashed or after 20 washes; both products were highly protective against biting. Laboratory tunnel bioassays confirmed the loss of biological activity of the PBO/deltamethrin-treated panel after washing. Conclusion Both PermaNet products were highly effective against susceptible Anopheles gambiae. As a long-lasting net to control or protect against pyrethroid
Skolarczyk, Justyna; Pekar, Joanna; Nieradko-Iwanicka, Barbara
Pyrethroids are biocides, which belong to the third generation of insecticides. They are used as biocides, insecticides and medicines. These agents react selectively, because they are less harmful to birds and mammals (due to poor intestinal absorption and rapid detoxification in the body of homeothermic organisms) and they are poisonous for fish and insects. The aim of the article is to present the current state of knowledge on the effects of pyrethroids on the immune system based on the latest scientific research. The mechanism of action of pyrethroids include the delaying closure of voltage- sensitive sodium and chloride channels (including GABA- dependent channels). These compounds are neurotoxic. Studies have shown that they cause numerous immune disorders contributing to lowering of immunity in humans and animals. Exposure to pyrethroids can cause inhibition of proliferation of peripheral blood leukocytes and reducing the concentration of IgG immunolgobulines. They also cause reduced macrophages and decrease in interleukin 2 (IL-2), interleukin 8 (IL-8), interleukin 12p70 (IL-12p70), and interferon γ (IFN-γ). Some of these compounds cause increase of liver weight and increase of bone marrow cellularity, and may induce apoptosis of the thymus. Pyrethroids can cause allergies and asthma. Their immunosuppressive effects can impair host resistance against infections. Exposure to these compounds can also contribute to induction of the cancer, especially in patients with impaired immune function.
Corine Ngufor; Andreas A Kudom; Pelagie Boko; Abibathou Odjo; David Malone; Mark Rowland
.... Methods The pyrrole chlorfenapyr and the pyrethroid alphacypermethrin were tested individually and as a mixture on mosquito nets in an experimental hut trial in southern Benin against pyrethroid...
Walker Edward D
Full Text Available Abstract Background A single base pair mutation in the sodium channel confers knock-down resistance to pyrethroids in many insect species. Its occurrence in Anopheles mosquitoes may have important implications for malaria vector control especially considering the current trend for large scale pyrethroid-treated bednet programmes. Screening Anopheles gambiae populations for the kdr mutation has become one of the mainstays of programmes that monitor the development of insecticide resistance. The screening is commonly performed using a multiplex Polymerase Chain Reaction (PCR which, since it is reliant on a single nucleotide polymorphism, can be unreliable. Here we present a reliable and potentially high throughput method for screening An. gambiae for the kdr mutation. Methods A Hot Ligation Oligonucleotide Assay (HOLA was developed to detect both the East and West African kdr alleles in the homozygous and heterozygous states, and was optimized for use in low-tech developing world laboratories. Results from the HOLA were compared to results from the multiplex PCR for field and laboratory mosquito specimens to provide verification of the robustness and sensitivity of the technique. Results and Discussion The HOLA assay, developed for detection of the kdr mutation, gives a bright blue colouration for a positive result whilst negative reactions remain colourless. The results are apparent within a few minutes of adding the final substrate and can be scored by eye. Heterozygotes are scored when a sample gives a positive reaction to the susceptible probe and the kdr probe. The technique uses only basic laboratory equipment and skills and can be carried out by anyone familiar with the Enzyme-linked immunosorbent assay (ELISA technique. A comparison to the multiplex PCR method showed that the HOLA assay was more reliable, and scoring of the plates was less ambiguous. Conclusion The method is capable of detecting both the East and West African kdr alleles
Stewart, Zachary P.; Oxborough, Richard M.; Tungu, Patrick K.; Kirby, Matthew J.; Rowland, Mark W.; Irish, Seth R.
Background Attractive toxic sugar bait (ATSB) sprayed onto vegetation has been successful in controlling Anopheles mosquitoes outdoors. Indoor application of ATSB has yet to be explored. The purpose of this study was to determine whether ATSB stations positioned indoors have the potential to kill host-seeking mosquitoes and constitute a new approach to control of mosquito-borne diseases. Methods Insecticides were mixed with dyed sugar solution and tested as toxic baits against Anopheles arabiensis, An. Gambiae s.s. and Culex quinquefasciatus in feeding bioassay tests to identify suitable attractant-insecticide combinations. The most promising ATSB candidates were then trialed in experimental huts in Moshi, Tanzania. ATSB stations were hung in huts next to untreated mosquito nets occupied by human volunteers. The proportions of mosquitoes killed in huts with ATSB treatments relative to huts with non-insecticide control treatments huts were recorded, noting evidence of dye in mosquito abdomens. Results In feeding bioassays, chlorfenapyr 0.5% v/v, boric acid 2% w/v, and tolfenpyrad 1% v/v, mixed in a guava juice-based bait, each killed more than 90% of pyrethroid-susceptible An. Gambiae s.s. and pyrethroid-resistant An. arabiensis and Cx. quinquefasciatus. In the hut trial, mortality rates of the three ATSB treatments ranged from 41-48% against An. arabiensis and 36-43% against Cx. quinquefasciatus and all were significantly greater than the control mortalities: 18% for An. arabiensis, 7% for Cx. quinquefasciatus (p<0.05). Mortality rates with ATSB were comparable to those with long lasting insecticidal nets previously tested against the same species in this area. Conclusions Indoor ATSB shows promise as a supplement to mosquito nets for controlling mosquitoes. Indoor ATSB constitute a novel application method for insecticide classes that act as stomach poisons and have not hitherto been exploited for mosquito control. Combined with LLIN, indoor use of ATSB has the
Zachary P Stewart
Full Text Available BACKGROUND: Attractive toxic sugar bait (ATSB sprayed onto vegetation has been successful in controlling Anopheles mosquitoes outdoors. Indoor application of ATSB has yet to be explored. The purpose of this study was to determine whether ATSB stations positioned indoors have the potential to kill host-seeking mosquitoes and constitute a new approach to control of mosquito-borne diseases. METHODS: Insecticides were mixed with dyed sugar solution and tested as toxic baits against Anopheles arabiensis, An. Gambiae s.s. and Culex quinquefasciatus in feeding bioassay tests to identify suitable attractant-insecticide combinations. The most promising ATSB candidates were then trialed in experimental huts in Moshi, Tanzania. ATSB stations were hung in huts next to untreated mosquito nets occupied by human volunteers. The proportions of mosquitoes killed in huts with ATSB treatments relative to huts with non-insecticide control treatments huts were recorded, noting evidence of dye in mosquito abdomens. RESULTS: In feeding bioassays, chlorfenapyr 0.5% v/v, boric acid 2% w/v, and tolfenpyrad 1% v/v, mixed in a guava juice-based bait, each killed more than 90% of pyrethroid-susceptible An. Gambiae s.s. and pyrethroid-resistant An. arabiensis and Cx. quinquefasciatus. In the hut trial, mortality rates of the three ATSB treatments ranged from 41-48% against An. arabiensis and 36-43% against Cx. quinquefasciatus and all were significantly greater than the control mortalities: 18% for An. arabiensis, 7% for Cx. quinquefasciatus (p<0.05. Mortality rates with ATSB were comparable to those with long lasting insecticidal nets previously tested against the same species in this area. CONCLUSIONS: Indoor ATSB shows promise as a supplement to mosquito nets for controlling mosquitoes. Indoor ATSB constitute a novel application method for insecticide classes that act as stomach poisons and have not hitherto been exploited for mosquito control. Combined with LLIN, indoor
Seixas, Gonçalo; Grigoraki, Linda; Weetman, David; Vicente, José Luís; Silva, Ana Clara; Pinto, João; Vontas, John; Sousa, Carla Alexandra
Aedes aegypti is a major mosquito vector of arboviruses, including dengue, chikungunya and Zika. In 2005, Ae. aegypti was identified for the first time in Madeira Island. Despite an initial insecticide-based vector control program, the species expanded throughout the Southern coast of the island, suggesting the presence of insecticide resistance. Here, we characterized the insecticide resistance status and the underlying mechanisms of two populations of Ae. aegypti from Madeira Island, Funchal and Paúl do Mar. WHO susceptibility bioassays indicated resistance to cyfluthrin, permethrin, fenitrothion and bendiocarb. Use of synergists significantly increased mortality rates, and biochemical assays indicated elevated activities of detoxification enzymes, suggesting the importance of metabolic resistance. Microarray-based transcriptome analysis detected significant upregulation in both populations of nine cytochrome P450 oxidase genes (including four known pyrethroid metabolizing enzymes), the organophosphate metabolizer CCEae3a, Glutathione-S-transferases, and multiple putative cuticle proteins. Genotyping of knockdown resistance loci linked to pyrethroid resistance revealed fixation of the 1534C mutation, and presence with moderate frequencies of the V1016I mutation in each population. Significant resistance to three major insecticide classes (pyrethroid, carbamate and organophosphate) is present in Ae. aegypti from Madeira Island, and appears to be mediated by multiple mechanisms. Implementation of appropriate resistance management strategies including rotation of insecticides with alternative modes of action, and methods other than chemical-based vector control are strongly advised to delay or reverse the spread of resistance and achieve efficient control.
Full Text Available Aedes aegypti is a major mosquito vector of arboviruses, including dengue, chikungunya and Zika. In 2005, Ae. aegypti was identified for the first time in Madeira Island. Despite an initial insecticide-based vector control program, the species expanded throughout the Southern coast of the island, suggesting the presence of insecticide resistance. Here, we characterized the insecticide resistance status and the underlying mechanisms of two populations of Ae. aegypti from Madeira Island, Funchal and Paúl do Mar.WHO susceptibility bioassays indicated resistance to cyfluthrin, permethrin, fenitrothion and bendiocarb. Use of synergists significantly increased mortality rates, and biochemical assays indicated elevated activities of detoxification enzymes, suggesting the importance of metabolic resistance. Microarray-based transcriptome analysis detected significant upregulation in both populations of nine cytochrome P450 oxidase genes (including four known pyrethroid metabolizing enzymes, the organophosphate metabolizer CCEae3a, Glutathione-S-transferases, and multiple putative cuticle proteins. Genotyping of knockdown resistance loci linked to pyrethroid resistance revealed fixation of the 1534C mutation, and presence with moderate frequencies of the V1016I mutation in each population.Significant resistance to three major insecticide classes (pyrethroid, carbamate and organophosphate is present in Ae. aegypti from Madeira Island, and appears to be mediated by multiple mechanisms. Implementation of appropriate resistance management strategies including rotation of insecticides with alternative modes of action, and methods other than chemical-based vector control are strongly advised to delay or reverse the spread of resistance and achieve efficient control.
The highly polymorphic CYP6M7 cytochrome P450 gene partners with the directionally selected CYP6P9a and CYP6P9b genes to expand the pyrethroid resistance front in the malaria vector Anopheles funestus in Africa.
Riveron, Jacob M; Ibrahim, Sulaiman S; Chanda, Emmanuel; Mzilahowa, Themba; Cuamba, Nelson; Irving, Helen; Barnes, Kayla G; Ndula, Miranda; Wondji, Charles S
Pyrethroid resistance in the major malaria vector Anopheles funestus is rapidly expanding across Southern Africa. It remains unknown whether this resistance has a unique origin with the same molecular basis or is multifactorial. Knowledge of the origin, mechanisms and evolution of resistance are crucial to designing successful resistance management strategies. Here, we established the resistance profile of a Zambian An. funestus population at the northern range of the resistance front. Similar to other Southern African populations, Zambian An. funestus mosquitoes are resistant to pyrethroids and carbamate, but in contrast to populations in Mozambique and Malawi, these insects are also DDT resistant. Genome-wide microarray-based transcriptional profiling and qRT-PCR revealed that the cytochrome P450 gene CYP6M7 is responsible for extending pyrethroid resistance northwards. Indeed, CYP6M7 is more over-expressed in Zambia [fold-change (FC) 37.7; 13.2 for qRT-PCR] than CYP6P9a (FC15.6; 8.9 for qRT-PCR) and CYP6P9b (FC11.9; 6.5 for qRT-PCR), whereas CYP6P9a and CYP6P9b are more highly over-expressed in Malawi and Mozambique. Transgenic expression of CYP6M7 in Drosophila melanogaster coupled with in vitro assays using recombinant enzymes and assessments of kinetic properties demonstrated that CYP6M7 is as efficient as CYP6P9a and CYP6P9b in conferring pyrethroid resistance. Polymorphism patterns demonstrate that these genes are under contrasting selection forces: the exceptionally diverse CYP6M7 likely evolves neutrally, whereas CYP6P9a and CYP6P9b are directionally selected. The higher variability of CYP6P9a and CYP6P9b observed in Zambia supports their lesser role in resistance in this country. Pyrethroid resistance in Southern Africa probably has multiple origins under different evolutionary forces, which may necessitate the design of different resistance management strategies.
Mougabure-Cueto, Gastón; Picollo, María Inés
Chagas disease is a chronic parasitic infection restricted to America. The disease is caused by the protozoa Trypanosoma cruzi, which is transmitted to human through the feces of infected triatomine insects. Because no treatment is available for the chronic forms of the disease, vector chemical control represents the best way to reduce the incidence of the disease. Chemical control has been based principally on spraying dwellings with insecticide formulations and led to the reduction of triatomine distribution and consequent interruption of disease transmission in several areas from endemic region. However, in the last decade it has been repeatedly reported the presence triatomnes, mainly Triatoma infestans, after spraying with pyrethroid insecticides, which was associated to evolution to insecticide resistance. In this paper the evolution of insecticide resistance in triatomines is reviewed. The insecticide resistance was detected in 1970s in Rhodnius prolixus and 1990s in R. prolixus and T. infestans, but not until the 2000s resistance to pyrthroids in T. infestans associated to control failures was described in Argentina and Bolivia. The main resistance mechanisms (i.e. enhanced metabolism, altered site of action and reduced penetration) were described in the T. infestans resistant to pyrethrods. Different resistant profiles were demonstrated suggesting independent origin of the different resistant foci of Argentina and Bolivia. The deltamethrin resistance in T. infestans was showed to be controlled by semi-dominant, autosomally inherited factors. Reproductive and developmental costs were also demonstrated for the resistant T. infestans. A discussion about resistance and tolerance concepts and the persistence of T. infestans in Gran Chaco region are presented. In addition, theoretical concepts related to toxicological, evolutionary and ecological aspects of insecticide resistance are discussed in order to understand the particular scenario of pyrethroid
T.S. Awolola, A.O. Oduola, I.O. Oyewole, J.B. Obansa, C.N. Amajoh
Full Text Available Background & objectives: Pyrethroid insecticide resistance in the malaria vector Anopheles gambiaeGiles is mainly associated with reduced target site sensitivity arising from a single point mutation inthe sodium channel gene, often referred to as knockdown resistance (kdr. This resistance mechanismis widespread in West Africa and was reported for the first time in Nigeria in 2002. Here we presentchanges in the susceptibility/resistance status of the molecular ‘M’ and ‘S’ forms of An. gambiae andthe frequency of the kdr alleles from 2002–05.Methods: Adult anophelines were sampled quarterly inside human dwellings from January 2002 toDecember 2005 and adults reared from wild larvae were identified using morphological keys. Samplesbelonging to the An. gambiae complex were subjected to PCR assays for species identification anddetection of molecular ‘M’ and ‘S’ forms. Insecticide susceptibility tests were carried out usingstandard WHO procedures and test kits only on 2–3 days old adult An. gambiae s.s. reared fromlarval collections. The kdr genotypes were determined in both live and dead specimens of An. gambiaes.s. using alleles-specific polymerase chain reaction diagnostic tests.Results: The overall collection showed that the molecular ‘S’ form was predominant (>60% but theproportions of both forms in the mosquito populations from 2002–05 were not statistically different.Both forms also occurred throughout the period without apparent relationship to wet or dry season.Insecticide susceptibility tests did not show any significant increase in the resistance status recordedfor either Permethrin or DDT from 2002–05, rather, an improvement in the susceptibility status ofthe mosquitoes to these insecticides was observed from 2004–05 relative to the tests performed in2002–03.Conclusion: The proportion of the molecular ‘M’ and ‘S’ form of An. gambiae and the kdr frequencieshave not increased significantly from 2002
Singh, Nirbhay Kumar; Jyoti; Vemu, Bhaskar; Nandi, Abhijit; Singh, Harkirat; Kumar, Rajender; Dumka, V K
Detection of resistance levels against cypermethrin and deltamethrin, the most commonly used synthetic pyrethroids (SPs) against Rhipicephalus (Boophilus) microplus collected from Moga, Punjab (India) was carried out using larval packet test. Results indicated the presence of resistance of level I and III against cypermethrin (resistance factors (RF) = 4.67) and deltamethrin (RF = 34.2), respectively. Adult immersion test was used to assess the acaricidal activity of aqueous and ethanolic extracts of leaves of Cymbopogon winterianus, Vitex negundo, and Withania somnifera along with roots of V. negundo against the SP resistant engorged females of R. (B.) microplus. The efficacy of various extracts was assessed by estimation of percent adult mortality, reproductive index (RI), percent inhibition of oviposition (%IO), and hatching rate. A concentration dependent increase in tick mortality was recorded which was more marked with various ethanolic extracts, and highest mortality was recorded in ticks treated with ethanolic extract of leaves of C. winterianus. The LC50 values were determined by applying regression equation analysis to the probit transformed data of mortality for various aqueous and ethanolic extracts. Acaricidal property was recorded to be higher in ethanolic extracts, and high activity was found with the ethanolic extract of leaves of C. winterianus with LC50 (95% CL) values of 0.46% (0.35-0.59%), followed by W. somnifera as 5.21% (4.45-6.09%) and V. negundo as 7.02% (4.58-10.74%). The egg mass weight of the live ticks treated with different concentrations of the various extract was significantly (p < 0.01) lower than that of control ticks; consequently, the RI and the %IO value of the treated ticks were reduced. Further, complete inhibition of hatching was recorded in eggs laid by ticks treated with ethanolic extracts of leaves of V. negundo and aqueous extracts of leaves of W. somnifera. The results of the current study indicate that extracts of C
Full Text Available Insecticide resistance has been known to be prevalent in several insect species including mosquito. It has become a major problem in vector control programme due to pesticide resistance through detoxification enzymes. The present study investigated the toxicity of Ae. aegypti to organophosphates and pyrethroid insecticide and biochemical mechanisms involved in insecticide resistance in larval population. Larval bioassay revealed an LC50 value of 0.734 ppm for dichlorvos and 1.140 ppm for λ-cyhalothrin exposure. Biochemical assay revealed increased activity of AChE (0.3 µmole/mg protein and GST in dichlorvos (1-1.5 µmole/mg protein treatment and esterase activity in λ-cyhalothrin treated compared to control activity. These studies suggest that AChE and GST is associated with organophosphate and esterase associated with pyrethroid resistance in Ae. aegypti.
The horn fly, Haematobia irritans L., is an obligate blood-feeding fly and the primary insect pest parasitizing cattle in the United States. Pesticide resistance has become a huge problem for cattle producers and although several mechanisms of resistance are possible, target site resistance is the m...
Andrew Y. Li; Kimbedy H. Lohmeyer; J. Allen Miller
A study was conducted at the Pressler ranch, near Kerrville, Texas, USA between 2002 and 2006 to determine the dynamics and mechanisms of resistance to permethrin in a field population of the horn fly, Haematobia irritans irritans (L.). Changes of resistance to pyrethroid insecticide associated with use of a pour-on formulation of cyfluthrin in 2002 and use of diazinon ear tags in subsequent years were studied using a filter paper bioassay technique and a polymerase chain reaction assay that detects two sodium channel mutations, kdr and super-kdr resistance alleles. A maximum of 294-fold resistance to permethrin was observed in the summer of 2002. A significant decrease in the resistance level was observed in spring 2003, and resistance continued to decline after animals were treated with diazinon ear tags. In response to pyrethroid treatments, the allelic kdr and super-kdr frequency increased from 56.3% to 93.8% and from 7.5% to 43.8%, respectively in 2002, and decreased significantly in 2003 when the pyrethroid insecticide was no longer used to treat animals. Females were found to have a higher allelic super-kdr frequency than males in 2002, while no difference was detected between males and females in the allelic kdr frequency. There was a significant positive correlation between frequencies of the sodium channel mutations and levels of permethrin resistance, suggesting that the sodium channel mutations, kdr and super-kdr, are the major mechanisms of resistance to pyrethroids in this horn fly population. Results of synergist bioassays also indicated possible contributions of two metabolic detoxification mechanisms, the mixed function oxidases (MFO) and glutathione S-trans-ferases (GST). Compared to a horn fly infestation of an untreated herd, treatments with the pyrethroid pour-on formulation failed to control horn flies at the Pressler ranch in 2002. Sustained control of horn flies was achieved with the use of diazinon ear tags in 2003 and subsequent years.
Ghosh, Srikanta; Tiwari, Shashi Shankar; Srivastava, Sharad; Sharma, Anil Kumar; Kumar, Sachin; Ray, D D; Rawat, A K S
Indian cattle ticks have developed resistance to commonly used acaricides and an attempt has been made to formulate an ecofriendly herbal preparation for the control of acaricide resistant ticks. A 95% ethanolic extract of Ricinus communis was used to test the efficacy against reference acaricide resistant lines by in vitro assay. In in vitro assay, the extract significantly affects the mortality rate of ticks in dose-dependent manner ranging from 35.0 ± 5.0 to 95.0 ± 5.0% with an additional effect on reproductive physiology of ticks by inhibiting 36.4-63.1% of oviposition. The leaf extract was found effective in killing 48.0, 56.7 and 60.0% diazinon, deltamethrin and multi-acaricide resistant ticks, respectively. However, the cidal and oviposition limiting properties of the extract were separated when the extract was fractionated with hexane, chloroform, n-butanol and water. The HPTLC finger printing profile of R. communis leaf extract under λ(max.) - 254 showed presence of quercetin, gallic acid, flavone and kaempferol which seemed to have synergistic acaricidal action. In vivo experiment resulted in 59.9% efficacy on Ist challenge, however, following 2nd challenge the efficacy was reduced to 48.5%. The results indicated that the 95% ethanolic leaf extract of R. communis can be used effectively in integrated format for the control of acaricide resistant ticks.
Pavlidi, N.; Monastirioti, M.; Daborn, P.; Van Leeuwen, T.; Vontas, J.
The emergence and spread of insecticide resistance in mosquitoes, such as the major vector of dengue and yellow fever Aedes aegypti, is a major public health problem. A number of studies have been conducted to-date aiming to identify specific molecular changes that are associated with the phenotype,
The occurrence of resistance in Varroa mite populations is a serious threat to the beekeeping industry and crops that rely on the honey bee for pollination. Integrated pest management strategies for control of this pest include the judicious use of insecticides. To monitor field populations of Varro...
Pavlidi, N.; Monastirioti, M.; Daborn, P.; Van Leeuwen, T.; Vontas, J.
The emergence and spread of insecticide resistance in mosquitoes, such as the major vector of dengue and yellow fever Aedes aegypti, is a major public health problem. A number of studies have been conducted to-date aiming to identify specific molecular changes that are associated with the phenotype,
Strachecka, Aneta; Borsuk, Grzegorz; Olszewski, Krzysztof; Paleolog, Jerzy; Lipiński, Zbigniew
The aim of this work was to determine the activity of proteases and protease inhibitors sampled from the body surface of tau-fluvalinate-sensitive and resistant V. destructor. Proteins were isolated from the tau-fluvalinate-sensitive and resistant mites, while mites untreated with tau-fluvalinate constituted the control. Subsequently, the following methodology was applied: protein concentration assay by the Lowry method - as modified by Schacterle and Pollack; assay of proteolytic activity in relation to various substrates (gelatine, haemoglobin, ovoalbumin, albumin, cytochrome C, casein) by the modified Anson method; identification of proteolytic activity in relation to diagnostic inhibitors of proteolytic enzymes (pepstatin A, PMSF, iodoacetamide, o-phenantrolin), using the Lee and Lin method; identification of acidic, neutral and basic protease activities by means of the modified Anson method; electrophoretic analysis of proteins in a polyacrylamide gel for protease detection with the Laemmli method and for protease inhibitor detection with the Felicioli method. The highest value of protein concentration was found in the tau-fluvalinate-sensitive V. destructor, while the highest activity levels of acidic, neutral and alkaline proteases were observed in the tau-fluvalinate-resistant mites. Aspartic, serine, thiolic and metallic proteases were found in the drug-resistant and drug-sensitive Varroa mites. The control samples were found to contain aspartic and serine proteases. In an acidic and alkaline environment, the results revealed a complete loss of inhibitor activities in the in vitro analyses and electrophoresis. Serine protease inhibitor activities (at pH 7.0) were high, especially in the group of tau-fluvalinate-resistant mites.
Synergism between demethylation inhibitor fungicides or gibberellin inhibitor plant growth regulators and bifenthrin in a pyrethroid-resistant population of Listronotus maculicollis (Coleoptera: Curculionidae).
Ramoutar, D; Cowles, R S; Requintina, E; Alm, S R
In 2007-2008, the "annual bluegrass weevil," Listronotus maculicollis Kirby (Coleoptera: Curculionidae), a serious pest of Poa annua L. (Poales: Poaceae) on U.S. golf courses, was shown to be resistant to two pyrethroids, bifenthrin and lambda-cyhalothrin. In 2008, we showed that bifenthrin resistance was principally mediated by oxidase detoxification (cytochrome P450 [P450]). P450s can be inhibited by demethylation inhibitor fungicides and gibberellin inhibitor plant growth regulators, both of which are commonly used on golf courses. We tested these compounds for synergistic activity with bifenthin against a pyrethroid-resistant population of L. maculicollis. The LD50 value for bifenthrin was significantly reduced from 87 ng per insect (without synergists) to 9.6-40 ng per insect after exposure to the fungicides fenarimol, fenpropimorph, prochloraz, propiconazole, and pyrifenox and the plant growth regulators flurprimidol, paclobutrazol, and trinexapac-ethyl. Simulated field exposure with formulated products registered for use on turf revealed enhanced mortality when adult weevils were exposed to bifenthrin (25% mortality, presented alone) combined with field dosages of propiconizole, fenarimol, flurprimidol, or trinexapac-ethyl (range, 49-70% mortality).
Corbel, Vincent; Chabi, Joseph; Dabiré, R. K.; Etang, J.; Nwane, P.; Pigeon, O.; Akogbeto, M.; Hougard, Jean-Marc
Background: Due to the spread of pyrethroid-resistance in malaria vectors in Africa, new strategies and tools are urgently needed to better control malaria transmission. The aim of this study was to evaluate the performances of a new mosaic long-lasting insecticidal net (LLIN), i.e. PermaNet (R) 3.0, against wild pyrethroid-resistant Anopheles gambiae s.l. in West and Central Africa. Methods: A multi centre experimental hut trial was conducted in Malanville (Benin), Vallee du Kou (Burkina Fas...
Pigeon Olivier; Nwane Philippe; Etang Josiane; Dabiré Roch K; Chabi Joseph; Corbel Vincent; Akogbeto Martin; Hougard Jean-Marc
Abstract Background Due to the spread of pyrethroid-resistance in malaria vectors in Africa, new strategies and tools are urgently needed to better control malaria transmission. The aim of this study was to evaluate the performances of a new mosaic long-lasting insecticidal net (LLIN), i.e. PermaNet® 3.0, against wild pyrethroid-resistant Anopheles gambiae s.l. in West and Central Africa. Methods A multi centre experimental hut trial was conducted in Malanville (Benin), Vallée du Kou (Burkina...
Denham, Steven; Eisen, Lars; Beaty, Meaghan; Beaty, Barry J; Black, William C; Saavedra-Rodriguez, Karla
We describe 2 new mosquito bioassays for use with insecticide-treated netting or other textiles. The 1st is a cylinder bioassay in which a mosquito is forced to contact treated material regardless of where it lands within the bioassay construct. The 2nd is a repellency/irritancy and biting-inhibition bioassay (RIBB) in which human arms and breath are used as attractants. Mosquitoes have the choice to pass through holes cut in untreated or treated netting to move from a center release chamber into side chambers to reach arms and potentially bite. Trials were conducted with pyrethroid-susceptible (New Orleans), moderately resistant (Hunucmá), and highly resistant (Vergel) strains of Aedes aegypti. Tests with netting treated with different pyrethroids demonstrated the utility of the cylinder bioassay to quantify knockdown and mortality following exposure to treated netting, and of the RIBB to quantify spatial repellency/contact irritancy of the treated netting and biting inhibition after females land on and then pass through holes in the treated netting. Both tested brands of pyrethroid-treated mosquitocidal netting (DuraNet® and NetProtect®) were effective against New Orleans but ineffective against Vergel strains. Mortality in the cylinder bioassay was 100% for New Orleans for all tested brands of treated netting, but only 10-14% for Vergel. Rates of passage through treated netting to reach a human arm in the RIBB were 10-15% for New Orleans versus 24-37% for Vergel. The reduction in biting after passage through treated netting, compared with untreated netting in the same trial replicates, was 12-39% for New Orleans versus ≤9% for Vergel.
Díaz, Pantoja Cristina; Alvarez Gavilán, Yudelmis; de Armas Rodríguez, Yaxsier; Bisset Lazcano, Juan A
In this paper, the level of resistance to four insecticides of 3 Blatella germanica strains collected from various places in the City of Havana province was evaluated. These strains were resistant to two pyrethroids (cypermethrin and lambda-cyalothrine) and to organophosphorate malathion but susceptible to carbamate propoxur. The values of alpha and beta esterases, acetylcholinesterase and gluthatione-S-transferase were estimated in three strains involved in the study. The results of the study showed high esterase activity in all the strains, mainly beta esterases and two of the three strains presented with high gluthation-S-transferase enzyme. No changes in acetylcholinesterase were demonstrated in relation to the reference strain. The association of levels of resistance to insecticides, the possible resistance mechanisms in each strain and the results of the enzymatic activity were also analyzed.
Soderlund, David M
The discovery of resmethrin almost five decades ago was the seminal event in the development of pyrethroid insecticides as important pest management tools, the value of which endures to this day. This brief review considers the development of pyrethroids from the perspective of the discovery of resmethrin. I describe the pathway to the discovery of resmethrin and the unique properties that differentiated it from the pyrethrins and earlier synthetic pyrethroids is described. I also summarize information on metabolic fate and mechanisms of selective toxicity, first elucidated with resmethrin, that have shaped our understanding of pyrethroid toxicology since that time. Finally, I review the discovery pathway that led from resmethrin to the development of the first photostable, agriculturally useful pyrethroids that established the importance of this insecticide class.
Full Text Available Abstract Background The development of mosquito nets pre-treated with insecticide, Long Lasting Impregnated Nets (LLINs that last the life span of the net, is a solution to the difficulty of the re-impregnation of conventional nets. Even if they showed a good efficacy in control conditions, their efficacy in the field, particularly in areas with resistance of Anopheles gambiae to pyrethroids, is not well documented. This study compares wide (Olyset® and small (Permanet® mesh LLINs in field conditions, using entomological parameters. Methods The two LLINs were tested in a rice-growing area of south-western Burkina Faso (West Africa with year around high density of the main malaria vector An. gambiae s.s. In the study village (VK6, there is a mixed population of two molecular forms of An. gambiae, the S-form which dominates during the rainy season and the M-form which dominates the rest of the year. The two LLINs Olyset® and Permanet® were distributed in the village and 20 matched houses were selected for comparison with four houses without treated nets. Results Mosquito entrance rate was ten fold higher in control houses than in houses with LLINs and there was no difference between the two net types. Among mosquitoes found in the houses, 36 % were dead in LLIN houses compared to 0% in control houses. Blood feeding rate was 80 % in control houses compared to 43 % in LLIN houses. The type of net did not significantly impact any of these parameters. No mosquitoes were found inside Permanet®, whereas dead or dying mosquitoes were collected inside the Olyset®. More than 60% of mosquitoes found on top or inside the nets had had blood meals from cattle, as shown by ELISA analysis. Conclusion The percentage of blood-fed mosquitoes in a bed net study does not necessarily determine net success. The efficacy of the two types of LLINs was comparable, during a period when the S-form of An. gambiae was carrying the kdr gene. Significantly higher numbers
Chlorfenapyr (A Pyrrole Insecticide) Applied Alone or as a Mixture with Alpha-Cypermethrin for Indoor Residual Spraying against Pyrethroid Resistant Anopheles gambiae sl: An Experimental Hut Study in Cove, Benin
Ngufor, C; Critchley, J; Fagbohoun, J; N'Guessan, R.; Todjinou, D; Rowland, M
Background Indoor spraying of walls and ceilings with residual insecticide remains a primary method of malaria control. Insecticide resistance in malaria vectors is a growing problem. Novel insecticides for indoor residual spraying (IRS) which can improve the control of pyrethroid resistant malaria vectors are urgently needed. Insecticide mixtures have the potential to improve efficacy or even to manage resistance in some situations but this possibility remains underexplored experimentally. C...
Hooper, David C; Jacoby, George A
Quinolone antimicrobials are synthetic and widely used in clinical medicine. Resistance emerged with clinical use and became common in some bacterial pathogens. Mechanisms of resistance include two categories of mutation and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes, DNA gyrase and DNA topoisomerase IV, are commonly in a localized domain of the GyrA and ParE subunits of the respective enzymes and reduce drug binding to the enzyme-DNA complex. Other resistance mutations occur in regulatory genes that control the expression of native efflux pumps localized in the bacterial membrane(s). These pumps have broad substrate profiles that include quinolones as well as other antimicrobials, disinfectants, and dyes. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids can confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is due to Qnr proteins that protect the target enzymes from quinolone action, one mutant aminoglycoside-modifying enzyme that also modifies certain quinolones, and mobile efflux pumps. Plasmids with these mechanisms often encode additional antimicrobial resistances and can transfer multidrug resistance that includes quinolones. Thus, the bacterial quinolone resistance armamentarium is large.
Full Text Available Abstract Background Due to the spread of pyrethroid-resistance in malaria vectors in Africa, new strategies and tools are urgently needed to better control malaria transmission. The aim of this study was to evaluate the performances of a new mosaic long-lasting insecticidal net (LLIN, i.e. PermaNet® 3.0, against wild pyrethroid-resistant Anopheles gambiae s.l. in West and Central Africa. Methods A multi centre experimental hut trial was conducted in Malanville (Benin, Vallée du Kou (Burkina Faso and Pitoa (Cameroon to investigate the exophily, blood feeding inhibition and mortality induced by PermaNet® 3.0 (i.e. a mosaic net containing piperonyl butoxide and deltamethrin on the roof comparatively to the WHO recommended PermaNet® 2.0 (unwashed and washed 20-times and a conventionally deltamethrin-treated net (CTN. Results The personal protection and insecticidal activity of PermaNet 3.0 and PermaNet® 2.0 were excellent (>80% in the "pyrethroid-tolerant" area of Malanville. In the pyrethroid-resistance areas of Pitoa (metabolic resistance and Vallée du Kou (presence of the L1014F kdr mutation, PermaNet® 3.0 showed equal or better performances than PermaNet® 2.0. It should be noted however that the deltamethrin content on PermaNet® 3.0 was up to twice higher than that of PermaNet® 2.0. Significant reduction of efficacy of both LLIN was noted after 20 washes although PermaNet® 3.0 still fulfilled the WHO requirement for LLIN. Conclusion The use of combination nets for malaria control offers promising prospects. However, further investigations are needed to demonstrate the benefits of using PermaNet® 3.0 for the control of pyrethroid resistant mosquito populations in Africa.
Ronald W Raab
Full Text Available Infestations of the common bed bug (Cimex lectularius L. have increased substantially in the United States in the past 10-15 years. The housing authority in Harrisonburg, Virginia, conducts heat-treatments after bed bugs are detected in a lower-income housing complex, by treating each infested unit at 60°C for 4-6 hours. However, a high frequency of recurrent infestations called into question the efficacy of this strategy. Genetic analysis using Bayesian clustering of polymorphic microsatellite loci from 123 bed bugs collected from 23 units from May 2012 to April 2013 in one building indicated that (a 16/21 (73% infestations were genetically similar, suggesting ineffective heat-treatments or reintroductions from within the building or from a common external source, followed by local spread of existing populations; and (b up to 5 of the infestations represented new genotypes, indicating that 5 new populations were introduced into this building in one year, assuming they were not missed in earlier screens. There was little to no gene flow among the 8 genetic clusters identified in the building. Bed bugs in the U.S. often possess one or both point mutations in the voltage-gated sodium channel, termed knockdown resistance (kdr, from valine to leucine (V419L and leucine to isoleucine (L925I that confer target-site resistance against pyrethroid insecticides. We found that 48/121 (40% bed bugs were homozygous for both kdr mutations (L419/I925, and a further 59% possessed at least one of the kdr mutations. We conclude that ineffective heat treatments, new introductions, reintroductions and local spread, and an exceptionally high frequency of pyrethroid resistance are responsible for chronic infestations in lower-income housing. Because heat treatments fail to protect from reintroductions, and pesticide use has not decreased the frequency of infestations, preventing new introductions and early detection are the most effective strategies to avoid bed bug
Full Text Available Abstract Background Anopheles gambiae, An. arabiensis, and An. funestus are widespread malaria vectors in Africa. Anopheles rivulorum is the next most widespread species in the An. funestus group. The role of An. rivulorum as a malaria vector has not been fully studied, although it has been found to be a minor or opportunistic transmitter of Plasmodium falciparum. Methods Mosquitoes were collected indoors over a 12-hour period using a light source attached to a rotating bottle collector in order to determine peak activity times and to provide DNA for meal source identification. Gravid female mosquitoes were collected indoors via an aspirator to generate F1 progeny for testing insecticidal susceptibility. Blood meal sources were identified using a multiplexed PCR assay for human and bovine cytochrome-B, and by matching sequences generated with primers targeting vertebrate and mammalian cytochrome-B segments to the Genbank database. Results Anopheles rivulorum fed on human blood in the early evening between 18:00 and 20:00, when insecticide-treated bed nets are not in use, and the presence of Plasmodium falciparum sporozoites in 0.70% of the An. rivulorum individuals tested was demonstrated. Susceptibility to permethrin, deltamethrin, and DDT is higher in An. rivulorum (84.8%, 91.4%, and 100%, respectively than in An. funestus s.s. (36.8%, 36.4%, and 70%, respectively, whereas mortality rates for propoxur and fenitrothion were 100% for both species. Resistance to pyrethroids was very high in An. funestus s.s. and the potential of the development of high resistance was suspected in An. rivulorum. Conclusion Given the tendency for An. rivulorum to be active early in the evening, the presence of P. falciparum in the species, and the potential for the development of pyrethroid resistance, we strongly advocate reconsideration of the latent ability of this species as an epidemiologically important malaria vector.
Raab, Ronald W; Moore, Julia E; Vargo, Edward L; Rose, Lucy; Raab, Julie; Culbreth, Madeline; Burzumato, Gracie; Koyee, Aurvan; McCarthy, Brittany; Raffaele, Jennifer; Schal, Coby; Vaidyanathan, Rajeev
Infestations of the common bed bug (Cimex lectularius L.) have increased substantially in the United States in the past 10-15 years. The housing authority in Harrisonburg, Virginia, conducts heat-treatments after bed bugs are detected in a lower-income housing complex, by treating each infested unit at 60°C for 4-6 hours. However, a high frequency of recurrent infestations called into question the efficacy of this strategy. Genetic analysis using Bayesian clustering of polymorphic microsatellite loci from 123 bed bugs collected from 23 units from May 2012 to April 2013 in one building indicated that (a) 16/21 (73%) infestations were genetically similar, suggesting ineffective heat-treatments or reintroductions from within the building or from a common external source, followed by local spread of existing populations; and (b) up to 5 of the infestations represented new genotypes, indicating that 5 new populations were introduced into this building in one year, assuming they were not missed in earlier screens. There was little to no gene flow among the 8 genetic clusters identified in the building. Bed bugs in the U.S. often possess one or both point mutations in the voltage-gated sodium channel, termed knockdown resistance (kdr), from valine to leucine (V419L) and leucine to isoleucine (L925I) that confer target-site resistance against pyrethroid insecticides. We found that 48/121 (40%) bed bugs were homozygous for both kdr mutations (L419/I925), and a further 59% possessed at least one of the kdr mutations. We conclude that ineffective heat treatments, new introductions, reintroductions and local spread, and an exceptionally high frequency of pyrethroid resistance are responsible for chronic infestations in lower-income housing. Because heat treatments fail to protect from reintroductions, and pesticide use has not decreased the frequency of infestations, preventing new introductions and early detection are the most effective strategies to avoid bed bug
Malima Robert; Maxwell Caroline; Magesa Stephen; Tungu Patrick; Masue Dennis; Sudi Wema; Myamba Joseph; Pigeon Olivier; Rowland Mark
Abstract Background Combination mosquito nets incorporating two unrelated insecticides or insecticide plus synergist are designed to control insecticide resistant mosquitoes. PermaNet 3.0 is a long-lasting combination net incorporating deltamethrin on the side panels and a mixture of deltamethrin and synergist piperonyl butoxide (PBO) on the top panel. PBO is an inhibitor of mixed function oxidases implicated in pyrethroid resistance. Method An experimental hut trial comparing PermaNet 3.0, P...
Li, Chun-xiao; Guo, Xiao-xia; Zhang, Ying-mei; Dong, Yan-de; Xing, Dan; Yan, Ting; Wang, Gang; Zhang, Heng-duan; Zhao, Tong-yan
Culex pipiens pallens and Cx. p. quinquefasciatus are important vectors of many diseases, such as West Nile fever and lymphatic filariasis. The widespread use of insecticides to control these disease vectors and other insect pests has led to insecticide resistance becoming common in these species. In this study, high throughout Illumina sequencing was used to identify hundreds of Cx. p. pallens and Cx. p. quinquefasciatus genes that were differentially expressed in response to insecticide exposure. The identification of these genes is a vital first step for more detailed investigation of the molecular mechanisms involved in insecticide resistance in Culex mosquitoes.
Full Text Available Aedes aegypti is a cosmopolite mosquito, vector of arboviruses. The worldwide studies of its insecticide resistance have demonstrated a strong loss of susceptibility to pyrethroids, the major class of insecticide used for vector control. French overseas territories such as French Guiana (South America, Guadeloupe islands (Lesser Antilles as well as New Caledonia (Pacific Ocean, have encountered such resistance.We initiated a research program on the pyrethroid resistance in French Guiana, Guadeloupe and New Caledonia. Aedes aegypti populations were tested for their deltamethrin resistance level then screened by an improved microarray developed to specifically study metabolic resistance mechanisms. Cytochrome P450 genes were implicated in conferring resistance. CYP6BB2, CYP6M11, CYP6N12, CYP9J9, CYP9J10 and CCE3 genes were upregulated in the resistant populations and were common to other populations at a regional scale. The implication of these genes in resistance phenomenon is therefore strongly suggested. Other genes from detoxification pathways were also differentially regulated. Screening for target site mutations on the voltage-gated sodium channel gene demonstrated the presence of I1016 and C1534.This study highlighted the presence of a common set of differentially up-regulated detoxifying genes, mainly cytochrome P450 genes in all three populations. GUA and GUY populations shared a higher number of those genes compared to CAL. Two kdr mutations well known to be associated to pyrethroid resistance were also detected in those two populations but not in CAL. Different selective pressures and genetic backgrounds can explain such differences. These results are also compared with those obtained from other parts of the world and are discussed in the context of integrative research on vector competence.
Blair, Jessica M A; Webber, Mark A; Baylay, Alison J; Ogbolu, David O; Piddock, Laura J V
Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.
MA Hong; CHEN Yibing; TAO Bo
This paper discussed mechanisms of herbicide-resistance. There are at least four mechanisms identified by which weeds become resistant to a herbicide. The two most common mechanisms are those involving metabolic reactions and changes in the deoxyribonucleic acid sequence (mutations) that alter the structure and features of the target proteins. The other two mechanisms involve either an alteration in the penetration or translocation of the herbicides to the target site or the depolarization of membrane within the weed.
Taşkın, Vatan; Başkurt, Sibel; Doğaç, Ersin; Taşkin, Belgin Göçmen
House flies were collected from 16 different provinces in the Aegean and Mediterranean regions of Turkey, and the frequencies of pyrethroid resistance-associated mutations in Vssc1 and CYP6D1 in these field-collected populations were studied. Although there is no organized resistance management program for house fly control in Turkey, it is known that different groups of insecticides, including pyrethroids, are used. The frequencies of both Vssc1 and CYP6D1 alleles were weighted toward the susceptibles, with Vssc1-susceptible alleles having higher frequencies in both regions (0.75 in Aegean and 0.69 in Mediterranean populations) than CYP6D1-susceptible alleles (0.65 in Aegean and 0.56 in Mediterranean populations). The frequencies of kdr-his alleles were higher than the frequencies of kdr alleles in these populations. While the frequencies of kdr-his alleles were close to each other in the Aegean (0.23) and Mediterranean (0.17) populations, the frequencies of kdr alleles remarkably differed in these two regions, with values of 0.02 and 0.14, respectively. In contrast to Europe, Asia, and the U.S.A., no super-kdr allele was detected in the samples from both regions. We identified six and eight different Vssc1+CYP6D1 genotype classes in the Aegean and Mediterranean regions, respectively. The three most common genotype classes in the regions were susceptible Vssc1 with heterozygous CYP6D1v1 (29%), sus/kdr-his1 with heterozygous CYP6D1v1 (23%), and susceptible Vssc1 with CYP6D1 (22%). The total frequencies of these three most common genotype classes (approximately 75%) obtained in our study were very close to the value obtained in Florida in a previous study, which was related by the similarity of temperature patterns between Florida and the corresponding regions of Turkey. This may reflect the lack of overwintering fitness cost associated with resistance alleles in both climates.
Experimental hut evaluation of bednets treated with an organophosphate (chlorpyrifos-methyl or a pyrethroid (lambdacyhalothrin alone and in combination against insecticide-resistant Anopheles gambiae and Culex quinquefasciatus mosquitoes
Full Text Available Abstract Background Pyrethroid resistant mosquitoes are becoming increasingly common in parts of Africa. It is important to identify alternative insecticides which, if necessary, could be used to replace or supplement the pyrethroids for use on treated nets. Certain compounds of an earlier generation of insecticides, the organophosphates may have potential as net treatments. Methods Comparative studies of chlorpyrifos-methyl (CM, an organophosphate with low mammalian toxicity, and lambdacyhalothrin (L, a pyrethroid, were conducted in experimental huts in Côte d'Ivoire, West Africa. Anopheles gambiae and Culex quinquefasciatus mosquitoes from the area are resistant to pyrethroids and organophosphates (kdr and insensitive acetylcholinesterase Ace.1R. Several treatments and application rates on intact or holed nets were evaluated, including single treatments, mixtures, and differential wall/ceiling treatments. Results and Conclusion All of the treatments were effective in reducing blood feeding from sleepers under the nets and in killing both species of mosquito, despite the presence of the kdr and Ace.1R genes at high frequency. In most cases, the effects of the various treatments did not differ significantly. Five washes of the nets in soap solution did not reduce the impact of the insecticides on A. gambiae mortality, but did lead to an increase in blood feeding. The three combinations performed no differently from the single insecticide treatments, but the low dose mixture performed encouragingly well indicating that such combinations might be used for controlling insecticide resistant mosquitoes. Mortality of mosquitoes that carried both Ace.1R and Ace.1S genes did not differ significantly from mosquitoes that carried only Ace.1S genes on any of the treated nets, indicating that the Ace.1R allele does not confer effective resistance to chlorpyrifos-methyl under the realistic conditions of an experimental hut.
Chlorfenapyr (A Pyrrole Insecticide) Applied Alone or as a Mixture with Alpha-Cypermethrin for Indoor Residual Spraying against Pyrethroid Resistant Anopheles gambiae sl: An Experimental Hut Study in Cove, Benin.
Ngufor, Corine; Critchley, Jessica; Fagbohoun, Josias; N'Guessan, Raphael; Todjinou, Damien; Rowland, Mark
Indoor spraying of walls and ceilings with residual insecticide remains a primary method of malaria control. Insecticide resistance in malaria vectors is a growing problem. Novel insecticides for indoor residual spraying (IRS) which can improve the control of pyrethroid resistant malaria vectors are urgently needed. Insecticide mixtures have the potential to improve efficacy or even to manage resistance in some situations but this possibility remains underexplored experimentally. Chlorfenapyr is a novel pyrrole insecticide which has shown potential to improve the control of mosquitoes which are resistant to current WHO-approved insecticides. The efficacy of IRS with chlorfenapyr applied alone or as a mixture with alpha-cypermeththrin (a pyrethroid) was evaluated in experimental huts in Cove, Southern Benin against wild free flying pyrethroid resistant Anopheles gambiae sl. Comparison was made with IRS with alpha-cypermethrin alone. Fortnightly 30-minute in situ cone bioassays were performed to assess the residual efficacy of the insecticides on the treated hut walls. Survival rates of wild An gambiae from the Cove hut site in WHO resistance bioassays performed during the trial were >90% with permethrin and deltamethrin treated papers. Mortality of free-flying mosquitoes entering the experimental huts was 4% in the control hut. Mortality with alpha-cypermethrin IRS did not differ from the control (5%, P>0.656). The highest mortality was achieved with chlorfenapyr alone (63%). The alpha-cypermethrin + chlorfenapyr mixture killed fewer mosquitoes than chlorfenapyr alone (43% vs. 63%, P<0.001). While the cone bioassays showed a more rapid decline in residual mortality with chlorfenapyr IRS to <30% after only 2 weeks, fortnightly mortality rates of wild free-flying An gambiae entering the chlorfenapyr IRS huts were consistently high (50-70%) and prolonged, lasting over 4 months. IRS with chlorfenapyr shows potential to significantly improve the control of malaria
Ishak, Intan H; Kamgang, Basile; Ibrahim, Sulaiman S; Riveron, Jacob M; Irving, Helen; Wondji, Charles S
Dengue control and prevention rely heavily on insecticide-based interventions. However, insecticide resistance in the dengue vector Aedes aegypti, threatens the continued effectiveness of these tools. The molecular basis of the resistance remains uncharacterised in many endemic countries including Malaysia, preventing the design of evidence-based resistance management. Here, we investigated the underlying molecular basis of multiple insecticide resistance in Ae. aegypti populations across Malaysia detecting the major genes driving the metabolic resistance. Genome-wide microarray-based transcription analysis was carried out to detect the genes associated with metabolic resistance in these populations. Comparisons of the susceptible New Orleans strain to three non-exposed multiple insecticide resistant field strains; Penang, Kuala Lumpur and Kota Bharu detected 2605, 1480 and 425 differentially expressed transcripts respectively (fold-change>2 and p-value ≤ 0.05). 204 genes were commonly over-expressed with monooxygenase P450 genes (CYP9J27, CYP6CB1, CYP9J26 and CYP9M4) consistently the most up-regulated detoxification genes in all populations, indicating that they possibly play an important role in the resistance. In addition, glutathione S-transferases, carboxylesterases and other gene families commonly associated with insecticide resistance were also over-expressed. Gene Ontology (GO) enrichment analysis indicated an over-representation of GO terms linked to resistance such as monooxygenases, carboxylesterases, glutathione S-transferases and heme-binding. Polymorphism analysis of CYP9J27 sequences revealed a high level of polymorphism (except in Joho Bharu), suggesting a limited directional selection on this gene. In silico analysis of CYP9J27 activity through modelling and docking simulations suggested that this gene is involved in the multiple resistance in Malaysian populations as it is predicted to metabolise pyrethroids, DDT and bendiocarb. The predominant
Ishak, Intan H.; Kamgang, Basile; Ibrahim, Sulaiman S.; Riveron, Jacob M.; Irving, Helen
Background Dengue control and prevention rely heavily on insecticide-based interventions. However, insecticide resistance in the dengue vector Aedes aegypti, threatens the continued effectiveness of these tools. The molecular basis of the resistance remains uncharacterised in many endemic countries including Malaysia, preventing the design of evidence-based resistance management. Here, we investigated the underlying molecular basis of multiple insecticide resistance in Ae. aegypti populations across Malaysia detecting the major genes driving the metabolic resistance. Methodology/Principal Findings Genome-wide microarray-based transcription analysis was carried out to detect the genes associated with metabolic resistance in these populations. Comparisons of the susceptible New Orleans strain to three non-exposed multiple insecticide resistant field strains; Penang, Kuala Lumpur and Kota Bharu detected 2605, 1480 and 425 differentially expressed transcripts respectively (fold-change>2 and p-value ≤ 0.05). 204 genes were commonly over-expressed with monooxygenase P450 genes (CYP9J27, CYP6CB1, CYP9J26 and CYP9M4) consistently the most up-regulated detoxification genes in all populations, indicating that they possibly play an important role in the resistance. In addition, glutathione S-transferases, carboxylesterases and other gene families commonly associated with insecticide resistance were also over-expressed. Gene Ontology (GO) enrichment analysis indicated an over-representation of GO terms linked to resistance such as monooxygenases, carboxylesterases, glutathione S-transferases and heme-binding. Polymorphism analysis of CYP9J27 sequences revealed a high level of polymorphism (except in Joho Bharu), suggesting a limited directional selection on this gene. In silico analysis of CYP9J27 activity through modelling and docking simulations suggested that this gene is involved in the multiple resistance in Malaysian populations as it is predicted to metabolise
Full Text Available Abstract Background As insecticide resistance may jeopardize the successful malaria control programmes in the Mekong region, a large investigation was previously conducted in the Mekong countries to assess the susceptibility of the main malaria vectors against DDT and pyrethroid insecticides. It showed that the main vector, Anopheles epiroticus, was highly pyrethroid-resistant in the Mekong delta, whereas Anopheles minimus sensu lato was pyrethroid-resistant in northern Vietnam. Anopheles dirus sensu stricto showed possible resistance to type II pyrethroids in central Vietnam. Anopheles subpictus was DDT- and pyrethroid-resistant in the Mekong Delta. The present study intends to explore the resistance mechanisms involved. Methods By use of molecular assays and biochemical assays the presence of the two major insecticide resistance mechanisms, knockdown and metabolic resistance, were assessed in the main malaria vectors of the Mekong region. Results Two FRET/MCA assays and one PCR-RFLP were developed to screen a large number of Anopheles populations from the Mekong region for the presence of knockdown resistance (kdr, but no kdr mutation was observed in any of the study species. Biochemical assays suggest an esterase mediated pyrethroid detoxification in An. epiroticus and An. subpictus of the Mekong delta. The DDT resistance in An. subpictus might be conferred to a high GST activity. The pyrethroid resistance in An. minimus s.l. is possibly associated with increased detoxification by esterases and P450 monooxygenases. Conclusion As different metabolic enzyme systems might be responsible for the pyrethroid and DDT resistance in the main vectors, each species may have a different response to alternative insecticides, which might complicate the malaria vector control in the Mekong region.
Full Text Available Pyrethroid insecticide-treated bed nets (ITNs help contribute to reducing malaria deaths in Africa, but their efficacy is threatened by insecticide resistance in some malaria mosquito vectors. We therefore assessed the evidence that resistance is attenuating the effect of ITNs on entomological outcomes.We included laboratory and field studies of African malaria vectors that measured resistance at the time of the study and used World Health Organization-recommended impregnation regimens. We reported mosquito mortality, blood feeding, induced exophily (premature exit of mosquitoes from the hut, deterrence, time to 50% or 95% knock-down, and percentage knock-down at 60 min. Publications were searched from 1 January 1980 to 31 December 2013 using MEDLINE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, Social Sciences Citation Index, African Index Medicus, and CAB Abstracts. We stratified studies into three levels of insecticide resistance, and ITNs were compared with untreated bed nets (UTNs using the risk difference (RD. Heterogeneity was explored visually and statistically. Included were 36 laboratory and 24 field studies, reported in 25 records. Studies tested and reported resistance inconsistently. Based on the meta-analytic results, the difference in mosquito mortality risk for ITNs compared to UTNs was lower in higher resistance categories. However, mortality risk was significantly higher for ITNs compared to UTNs regardless of resistance. For cone tests: low resistance, risk difference (RD 0.86 (95% CI 0.72 to 1.01; moderate resistance, RD 0.71 (95% CI 0.53 to 0.88; high resistance, RD 0.56 (95% CI 0.17 to 0.95. For tunnel tests: low resistance, RD 0.74 (95% CI 0.61 to 0.87; moderate resistance, RD 0.50 (95% CI 0.40 to 0.60; high resistance, RD 0.39 (95% CI 0.24 to 0.54. For hut studies: low resistance, RD 0.56 (95% CI 0.43 to 0.68; moderate resistance, RD 0.39 (95% CI 0.16 to 0.61; high resistance, RD 0
DeMicco, Amy; Cooper, Keith R; Richardson, Jason R; White, Lori A
Pyrethroid insecticides are one of the most commonly used residential and agricultural insecticides. Based on the increased use of pyrethroids and recent studies showing that pregnant women and children are exposed to pyrethroids, there are concerns over the potential for developmental neurotoxicity. However, there have been relatively few studies on the developmental neurotoxicity of pyrethroids. In this study, we sought to investigate the developmental toxicity of six common pyrethroids, three type I compounds (permethrin, resmethrin, and bifenthrin) and three type II compounds (deltamethrin, cypermethrin, and lambda-cyhalothrin), and to determine whether zebrafish embryos may be an appropriate model for studying the developmental neurotoxicity of pyrethroids. Exposure of zebrafish embryos to pyrethroids caused a dose-dependent increase in mortality and pericardial edema, with type II compounds being the most potent. At doses approaching the LC(50), permethrin and deltamethrin caused craniofacial abnormalities. These findings are consistent with mammalian studies demonstrating that pyrethroids are mildly teratogenic at very high doses. However, at lower doses, body axis curvature and spasms were observed, which were reminiscent of the classic syndromes observed with pyrethroid toxicity. Treatment with diazepam ameliorated the spasms, while treatment with the sodium channel antagonist MS-222 ameliorated both spasms and body curvature, suggesting that pyrethroid-induced neurotoxicity is similar in zebrafish and mammals. Taken in concert, these data suggest that zebrafish may be an appropriate alternative model to study the mechanism(s) responsible for the developmental neurotoxicity of pyrethroid insecticides and aid in identification of compounds that should be further tested in mammalian systems.
Tran, Truc T; Munita, Jose M; Arias, Cesar A
Daptomycin (DAP) is a cyclic lipopeptide with in vitro activity against a variety of Gram-positive pathogens, including multidrug-resistant organisms. Since its introduction into clinical practice in 2003, DAP has become an important key frontline antibiotic for severe or deep-seated infections caused by Gram-positive organisms. Unfortunately, DAP resistance (DAP-R) has been extensively documented in clinically important organisms such as Staphylococcus aureus, Enterococcus spp., and Streptococcus spp. Studies on the mechanisms of DAP-R in Bacillus subtilis and other Gram-positive bacteria indicate that the genetic pathways of DAP-R are diverse and complex. However, a common phenomenon emerging from these mechanistic studies is that DAP-R is associated with important adaptive changes in cell wall and cell membrane homeostasis with critical changes in cell physiology. Findings related to these adaptive changes have provided novel insights into the genetics and molecular mechanisms of bacterial cell envelope stress response and the manner in which Gram-positive bacteria cope with the antimicrobial peptide attack and protect vital structures of the cell envelope, such as the cell membrane. In this review, we will examine the most recent findings related to the molecular mechanisms of resistance to DAP in relevant Gram-positive pathogens and discuss the clinical implications for therapy against these important bacteria.
Sutthanont, Nataya; Choochote, Wej; Tuetun, Benjawan; Junkum, Anuluck; Jitpakdi, Atchariya; Chaithong, Udom; Riyong, Doungrat; Pitasawat, Benjawan
The chemical compositions and larvicidal potential against mosquito vectors of selected essential oils obtained from five edible plants were investigated in this study. Using a GC/MS, 24, 17, 20, 21, and 12 compounds were determined from essential oils of Citrus hystrix, Citrus reticulata, Zingiber zerumbet, Kaempferia galanga, and Syzygium aromaticum, respectively. The principal constituents found in peel oil of C. hystrix were beta-pinene (22.54%) and d-limonene (22.03%), followed by terpinene-4-ol (17.37%). Compounds in C. reticulata peel oil consisted mostly of d-limonene (62.39%) and gamma-terpinene (14.06%). The oils obtained from Z. zerumbet rhizome had alpha-humulene (31.93%) and zerumbone (31.67%) as major components. The most abundant compounds in K. galanga rhizome oil were 2-propeonic acid (35.54%), pentadecane (26.08%), and ethyl-p-methoxycinnamate (25.96%). The main component of S. aromaticum bud oil was eugenol (77.37%), with minor amounts of trans-caryophyllene (13.66%). Assessment of larvicidal efficacy demonstrated that all essential oils were toxic against both pyrethroid-susceptible and resistant Ae. aegypti laboratory strains at LC50, LC95, and LC99 levels. In conclusion, we have documented the promising larvicidal potential of essential oils from edible herbs, which could be considered as a potentially alternative source for developing novel larvicides to be used in controlling vectors of mosquito-borne disease.
Duran, George E.; Wang, Yan C.; Francisco, E. Brian; Rose, John C.; Martinez, Francisco J.; Coller, John; Brassard, Diana; Vrignaud, Patricia; Sikic, Branimir I.
We studied mechanisms of resistance to the novel taxane cabazitaxel in established cellular models of taxane resistance. We also developed cabazitaxel-resistant variants from MCF-7 breast cancer cells by stepwise selection in drug alone (MCF-7/CTAX) or drug plus the transport inhibitor PSC-833 (MCF-7/CTAX-P). Among multidrug resistant (MDR) variants, cabazitaxel was relatively less cross-resistant than paclitaxel and docetaxel (15 vs. 200-fold in MES-SA/Dx5 and 9 vs. 60-fold in MCF-7/TxT50, respectively). MCF-7/TxTP50 cells that were negative for MDR but had 9-fold resistance to paclitaxel were also 9-fold resistant to cabazitaxel. Selection with cabazitaxel alone (MCF-7/CTAX) yielded 33-fold resistance to cabazitaxel, 52-fold resistance to paclitaxel, activation of ABCB1, and 3-fold residual resistance to cabazitaxel with MDR inhibition. The MCF-7/CTAX-P variant did not express ABCB1, nor did it efflux rhodamine-123, BODIPY-labeled paclitaxel, and [3H]-docetaxel. These cells are hypersensitive to depolymerizing agents (vinca alkaloids and colchicine), have reduced baseline levels of stabilized microtubules, and impaired tubulin polymerization in response to taxanes (cabazitaxel or docetaxel) relative to MCF-7 parental cells. Class III β-tubulin (TUBB3) RNA and protein were elevated in both MCF-7/CTAX and MCF-7/CTAX-P. Decreased BRCA1 and altered epithelial-mesenchymal transition (EMT) markers are also associated with cabazitaxel resistance in these MCF-7 variants, and may serve as predictive biomarkers for its activity in the clinical setting. In summary, cabazitaxel resistance mechanisms include MDR (although at a lower level than paclitaxel and docetaxel), and alterations in microtubule dynamicity, as manifested by higher expression of TUBB3, decreased BRCA1, and by the induction of EMT. PMID:25416788
Howard, A.F.V.; Koenraadt, C.J.M.; Farenhorst, M.; Knols, B.G.J.; Takken, W.
BACKGROUND: Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have
Howard, A.F.V.; Koenraadt, C.J.M.; Farenhorst, M.; Knols, B.G.J.; Takken, W.
Background: Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have
Full Text Available Abstract Background Scaling up of long-lasting insecticidal nets (LLINs and indoor residual spraying (IRS with support from the Global Fund and President's Malaria Initiative is providing increased opportunities for malaria control in Africa. The most cost-effective and longest-lasting residual insecticide DDT is also the most environmentally persistent. Alternative residual insecticides exist, but are too short-lived or too expensive to sustain. Dow Agrosciences have developed a microencapsulated formulation (CS of the organophosphate chlorpyrifos methyl as a cost-effective, long-lasting alternative to DDT. Methods Chlorpyrifos methyl CS was tested as an IRS or ITN treatment in experimental huts in an area of Benin where Anopheles gambiae and Culex quinquefasiactus are resistant to pyrethroids, but susceptible to organophosphates. Efficacy and residual activity was compared to that of DDT and the pyrethroid lambdacyalothrin. Results IRS with chlorpyrifos methyl killed 95% of An. gambiae that entered the hut as compared to 31% with lambdacyhalothrin and 50% with DDT. Control of Cx. quinquefasciatus showed a similar trend; although the level of mortality with chlorpyrifos methyl was lower (66% it was still much higher than for DDT (14% or pyrethroid (15% treatments. Nets impregnated with lambdacyhalothrin were compromized by resistance, killing only 30% of An. gambiae and 8% of Cx. quinquefasciatus. Nets impregnated with chlorpyrifos methyl killed more (45% of An gambiae and 15% of Cx. quinquefasciatus, but its activity on netting was of short duration. Contact bioassays on the sprayed cement-sand walls over the nine months of monitoring showed no loss of activity of chlorpyrifos methyl, whereas lambdacyhalothrin and DDT lost activity within a few months of spraying. Conclusion As an IRS treatment against pyrethroid resistant mosquitoes chlorpyrifos methyl CS outperformed DDT and lambdacyhalothrin. In IRS campaigns, chlorpyrifos methyl CS should
Wissam eEl Hage
Full Text Available Depression is one of the most frequent and severe mental disorder. Since the discovery of antidepressant properties of the imipramine and then after of other tricyclic compounds, several classes of psychotropic drugs have shown be effective in treating major depressive disorder. However, there is a wide range of variability in response to antidepressants that might lead to non response or partial response or in increased rate of relapse or recurrence. The mechanisms of response to antidepressant therapy are poorly understood, and few biomarkers are available than can predict response to pharmacotherapy. Here, we will first review markers that can be used to predict response to pharmacotherapy, such as markers of drug metabolism or blood-brain barrier function, the activity of specific brain areas or neurotransmitter systems, hormonal dysregulations or plasticity, and related molecular targets. We will describe both clinical and preclinical studies and describe factors that might affect the expression of these markers, including environmental or genetic factors and comorbidities. This information will permit us to suggest practical recommendations and innovative treatment strategies to improve therapeutic outcomes.
El-Hage, Wissam; Leman, Samuel; Camus, Vincent; Belzung, Catherine
Depression is one of the most frequent and severe mental disorder. Since the discovery of antidepressant (AD) properties of the imipramine and then after of other tricyclic compounds, several classes of psychotropic drugs have shown be effective in treating major depressive disorder (MDD). However, there is a wide range of variability in response to ADs that might lead to non response or partial response or in increased rate of relapse or recurrence. The mechanisms of response to AD therapy are poorly understood, and few biomarkers are available than can predict response to pharmacotherapy. Here, we will first review markers that can be used to predict response to pharmacotherapy, such as markers of drug metabolism or blood-brain barrier (BBB) function, the activity of specific brain areas or neurotransmitter systems, hormonal dysregulations or plasticity, and related molecular targets. We will describe both clinical and preclinical studies and describe factors that might affect the expression of these markers, including environmental or genetic factors and comorbidities. This information will permit us to suggest practical recommendations and innovative treatment strategies to improve therapeutic outcomes. PMID:24319431
Hien, Aristide Sawdetuo; Soma, Dieudonné Diloma; Hema, Omer; Bayili, Bazoma; Namountougou, Moussa; Gnankiné, Olivier; Baldet, Thierry; Diabaté, Abdoulaye; Dabiré, Kounbobr Roch
Many studies have shown the role of agriculture in the selection and spread of resistance of Anopheles gambiae s.l. to insecticides. However, no study has directly demonstrated the presence of insecticides in breeding sources as a source of selection for this resistance. It is in this context that we investigated the presence of pesticide residues in breeding habitats and their formal involvement in vector resistance to insecticides in areas of West Africa with intensive farming. This study was carried out from June to November 2013 in Dano, southwest Burkina Faso in areas of conventional (CC) and biological cotton (BC) growing. Water and sediment samples collected from breeding sites located near BC and CC fields were submitted for chromatographic analysis to research and titrate the residual insecticide content found there. Larvae were also collected in these breeding sites and used in toxicity tests to compare their mortality to those of the susceptible strain, Anopheles gambiae Kisumu. All tested mosquitoes (living and dead) were analyzed by PCR for species identification and characterization of resistance genes. The toxicity analysis of water from breeding sites showed significantly lower mortality rates in breeding site water from biological cotton (WBC) growing sites compared to that from conventional cotton (WCC) sites respective to both An. gambiae Kisumu (WBC: 80.75% vs WCC: 92.75%) and a wild-type strain (49.75% vs 66.5%). The allele frequencies L1014F, L1014S kdr, and G116S ace -1R mutations conferring resistance, respectively, to pyrethroids and carbamates / organophosphates were 0.95, 0.4 and 0.12. Deltamethrin and lambda-cyhalothrin were identified in the water samples taken in October/November from mosquitoes breeding in the CC growing area. The concentrations obtained were respectively 0.0147ug/L and 1.49 ug/L to deltamethrin and lambdacyhalothrin. Our results provided evidence by direct analysis (biological and chromatographic tests) of the role
Samir Bhattacharya; Debleena Dey; Sib Sankar Roy
Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, leading to a reduced amount of IR protein in insulin target cells. PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of this important area, emphasizing the current status.
Howard, A.F.V.; Koenraadt, C.J.M.; Farenhorst, M.; Knols, B.G.J.; Takken, W.
BACKGROUND: Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have pr
Howard, A.F.V.; Koenraadt, C.J.M.; Farenhorst, M.; Knols, B.G.J.; Takken, W.
Background: Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have pr
Trung Ho; Speybroeck Niko; Berkvens Dirk; Chinh Vu; Van Bortel Wim; Coosemans Marc
Abstract Background In this study, the efficacy of insecticide-treated nets was evaluated in terms of deterrence, blood-feeding inhibition, induced exophily and mortality on a wild resistant population of Anopheles epiroticus in southern Vietnam, in order to gain insight into the operational consequences of the insecticide resistance observed in this malaria vector in the Mekong delta. Method An experimental station, based on the model of West Africa and adapted to the behaviour of the target...
In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the pathophy
In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the pathophy
In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the
Knols Bart GJ
Full Text Available Abstract Background Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have previously examined the effects of entomopathogenic fungi against adult mosquitoes, most application methods used cannot be readily deployed in the field. Because the fungi are biological organisms it is important to test potential field application methods that will not adversely affect them. The two objectives of this study were to investigate any differences in fungal susceptibility between an insecticide-resistant and insecticide-susceptible strain of Anopheles gambiae sensu stricto, and to test a potential field application method with respect to the viability and virulence of two fungal species Methods Pieces of white polyester netting were dipped in Metarhizium anisopliae ICIPE-30 or Beauveria bassiana IMI391510 mineral oil suspensions. These were kept at 27 ± 1°C, 80 ± 10% RH and the viability of the fungal conidia was recorded at different time points. Tube bioassays were used to infect insecticide-resistant (VKPER and insecticide-susceptible (SKK strains of An. gambiae s.s., and survival analysis was used to determine effects of mosquito strain, fungus species or time since fungal treatment of the net. Results The resistant VKPER strain was significantly more susceptible to fungal infection than the insecticide-susceptible SKK strain. Furthermore, B. bassiana was significantly more virulent than M. anisopliae for both mosquito strains, although this may be linked to the different viabilities of these fungal species. The viability of both fungal species decreased significantly one day after application onto polyester netting when compared to the viability of conidia remaining in suspension. Conclusions The insecticide-resistant
Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed. PMID:23865047
Wieczorek, Kinga; Osek, Jacek
Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed.
Temporal frequency of knockdown resistance mutations, F1534C and V1016G, in Aedes aegypti in Chiang Mai city, Thailand and the impact of the mutations on the efficiency of thermal fogging spray with pyrethroids.
Plernsub, Suriya; Saingamsook, Jassada; Yanola, Jintana; Lumjuan, Nongkran; Tippawangkosol, Pongsri; Walton, Catherine; Somboon, Pradya
In Thailand, control of dengue outbreaks is currently attained by the use of space sprays, particularly thermal fogging using pyrethroids, with the aim of killing infected Aedes mosquito vectors in epidemic areas. However, the principal dengue vector, Aedes aegypti, is resistant to pyrethroids conferred mainly by mutations in the voltage-gated sodium channel gene, F1534C and V1016G, termed knockdown resistance (kdr). The objectives of this study were to determine the temporal frequencies of F1534C and V1016G in Ae. aegypti populations in relation to pyrethroid resistance in Chiang Mai city, and to evaluate the impact of the mutations on the efficacy of thermal fogging with the pyrethroid deltamethrin. Larvae and pupae were collected from several areas around Chiang Mai city during 2011-2015 and reared to adulthood for bioassays for deltamethrin susceptibility. These revealed no trend of increasing deltamethrin resistance during the study period (mortality 58.0-69.5%, average 62.8%). This corresponded to no overall change in the frequencies of the C1534 allele (0.55-0.66, average 0.62) and G1016 allele (0.34-0.45, average 0.38), determined using allele specific amplification. Only three genotypes of kdr mutations were detected: C1534 homozygous (VV/CC); G1016/C1534 double heterozygous (VG/FC); and G1016 homozygous (GG/FF) indicating that the F1534C and V1016G mutations occurred on separate haplotypic backgrounds and a lack of recombination between them to date. The F1 progeny females were used to evaluate the efficacy of thermal fogging spray with Damthrin-SP(®) (deltamethrin+S-bioallethrin+piperonyl butoxide) using a caged mosquito bioassay. The thermal fogging spray killed 100% and 61.3% of caged mosquito bioassay placed indoors and outdoors, respectively. The outdoor spray had greater killing effect on C1534 homozygous and had partially effect on double heterozygous mosquitoes, but did not kill any G1016 homozygous mutants living outdoors. As this selection
The horn fly, Haematobia irritans irritans (Linnaeus, 1758), is an important pest that causes significant economic losses to the livestock industry, but insecticide resistance in horn fly populations has made horn fly control increasingly difficult to achieve. In this study, we developed a multiplex...
Xu, Qiang; Liu, Huqi; Zhang, Lee; Liu, Nannan
Two mosquito strains of Culex quinquefasciatus (Say), MAmCq(G0) and HAmCq(G0), were collected from Mobile and Huntsville, Alabama, respectively. MAmCq(G0) and HAmCq(G0) were further selected in the laboratory with permethrin for one and three generations, respectively. The levels of resistance to permethrin in MAmCq(G1) (after one-generation selection) and HAmCq(G3) (after three-generation selection) increased rapidly. Resistance to permethrin in MAmCq(G1) and HAmCq(G3) was partially suppressed by piperonyl butoxide (PBO), S,S,S-tributylphosphorotrithioate (DEF) and diethyl maleate (DEM), inhibitors of cytochrome P450 monooxygenases, hydrolases and glutathione S-transferases (GST), respectively, suggesting these three enzyme families are important in conferring permethrin resistance in both strains. A substitution of leucine to phenylalanine (L to F) resulting from a single nucleotide polymorphism (SNP), termed the kdr mutation, in the para-homologous sodium channel gene has been reported as a very common mutation associated with pyrethroid resistance of insects. A 341-bp sodium channel gene fragment, where the kdr mutation resides, was generated by PCR from genomic DNAs of Cx. quinquefasciatus strains. We found that the kdr mutation was present in both permethrin-selected and unselected HAmCq and MAmCq mosquito populations, suggesting that the kdr mutation plays the role in permethrin resistance. There was no significant change in the frequency and heterozygosity of the A to T SNP for the kdr allele between permethrin-selected and unselected MAmCq and HAmCq mosquitoes, indicating that other mechanisms are involved in the evolution of resistance in mosquitoes selected by permethrin in the laboratory. Copyright 2005 Society of Chemical Industry.
Koffi, Alphonsine A; Ahoua Alou, Ludovic P; Djenontin, Armel; Kabran, Jean-Paul K; Dosso, Youssouf; Kone, Aboubacar; Moiroux, Nicolas; Pennetier, Cedric
Pyrethroid resistance in malaria vectors has spread across sub-Saharan Africa. Alternative tools and molecules are urgently needed for effective vector control. One of the most promising strategies to prevent or delay the development of resistance is to use at least two molecules having unrelated modes of action in combination in the same bed net. We evaluated in experimental huts in Côte d'Ivoire, a new polyethylene long-lasting insecticidal net (LN) product, Olyset® Duo, incorporating permethrin (PER) and pyriproxyfen (PPF), an insect growth regulator (IGR). PPF alone or in combination with permethrin had a significant impact on fertility (7-12% reduction relative to control) and no effect on fecundity of wild multi-resistant An. gambiae s.s. These results triggered crucial research questions on the behaviour of targeted mosquitoes around the LN. To maximize the sterilizing effect of PPF in the combination, there would be a need for a trade-off between the necessary contact time of the insect with PPF and the surface content of the pyrethroid insecticide that is bioavailable and induces excito-repellency. © A.A. Koffi et al., published by EDP Sciences, 2015.
Koffi Alphonsine A.
Full Text Available Pyrethroid resistance in malaria vectors has spread across sub-Saharan Africa. Alternative tools and molecules are urgently needed for effective vector control. One of the most promising strategies to prevent or delay the development of resistance is to use at least two molecules having unrelated modes of action in combination in the same bed net. We evaluated in experimental huts in Côte d’Ivoire, a new polyethylene long-lasting insecticidal net (LN product, Olyset® Duo, incorporating permethrin (PER and pyriproxyfen (PPF, an insect growth regulator (IGR. PPF alone or in combination with permethrin had a significant impact on fertility (7–12% reduction relative to control and no effect on fecundity of wild multi-resistant An. gambiae s.s. These results triggered crucial research questions on the behaviour of targeted mosquitoes around the LN. To maximize the sterilizing effect of PPF in the combination, there would be a need for a trade-off between the necessary contact time of the insect with PPF and the surface content of the pyrethroid insecticide that is bioavailable and induces excito-repellency.
Bailey, Kate M; Wojtkowiak, Jonathan W; Cornnell, Heather H; Ribeiro, Maria C; Balagurunathan, Yoganand; Hashim, Arig Ibrahim; Gillies, Robert J
Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, we confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.
Anderson, John F; Cowles, Richard S
Relative increases of bed bug, Cimex lectularius L., populations are probably due in large measure to their resistance to pyrethroids, which have been used extensively against urban pests. A Connecticut population of bed bugs was assessed for sensitivity to pyrethroids and exposed to commonly-used commercial insecticides applied to various substrates on which the residues were allowed to age for 0-24 wk. Type I and type II pyrethroids differed in toxicity when applied at a high dosage (1 microg) per bed bug. Some type II pyrethroids (cyfluthrin, lambda-cyhalothrin, cis-cypermethrin, and deltamethrin) caused > 80% mortality, whereas exposure to type I pyrethroids caused 0.95) an exponential rise to a maximum model from which the survival half-life (S1/2) was calculated directly. Tempo Dust (Bayer Environmental Science, Montvale, NJ) killed bed bugs relatively quickly, as did Syloid 244 (Grace Davison, Columbia, MD) and Drione (Bayer Environmental Science, Montvale, NJ) on hardboard and mattress fabric substrates (S1/2 Companies, Waterbury, CT), displayed reduced residual toxicity as they aged; the mortality was < 50% on some substrates after 4 d. Desiccant dusts, with their physical mode of action and long residual activity, appear to be superior to sprayable pyrethroid products for killing bed bugs.
Sulaiman S Ibrahim
Full Text Available Scale up of Long Lasting Insecticide Nets (LLINs has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies.
Unique biochemical and molecular biological mechanism of synergistic actions of formamidine compounds on selected pyrethroid and neonicotinoid insecticides on the fourth instar larvae of Aedes aegypti (Diptera: Culicidae).
Ahmed, Mohamed Ahmed Ibrahim; Vogel, Christoph F A; Matsumura, Fumio
We recently reported that formamidine pesticides such as amitraz and chlordimeform effectively synergize toxic actions of certain pyrethroid and neonicotinoid insecticides in some insect species on the 4th instar larvae of Aedes aegypti. Here we studied the biochemical basis of the synergistic actions of the formamidines in amplifying the toxicity of neonicotinoids and pyrethroids such as dinotefuran and thiamethoxam, as well as deltamethrin-fenvalerate type of pyrethroids. We tested the hypothesis that their synergistic actions are mediated by the octopamine receptor, and that the major consequence of octopamine receptor activation is induction of trehalase to increase glucose levels in the hemolymph. The results show that formamidines cause a significant up-regulation of the octopamine receptor and trehalase mRNA expressions. Furthermore, formamidines significantly elevate levels of free glucose when co-treated with dinotefuran, deltamethrin and fenvalerate, but not with permethrin or fenitrothion, which showed no synergistic toxic effects with formamidines. These results support the conclusion that the main mode of synergism is based on the ability to activate the octopamine receptor, which is particularly effective with insecticides causing hyperexcitation-induced glucose release and consequently leading to quick energy exhaustion.
Sikulu, Maggy T; Majambere, Silas; Khatib, Bakar O; Ali, Abdullah S; Hugo, Leon E; Dowell, Floyd E
We report on the accuracy of using near-infrared spectroscopy (NIRS) to predict the age of Anopheles mosquitoes reared from wild larvae and a mixed age-wild adult population collected from pit traps after exposure to pyrethroids. The mosquitoes reared from wild larvae were estimated as 8 d for both susceptible and resistant groups. The age structure of wild-collected mosquitoes was not significantly different for the pyrethroid-susceptible and pyrethroid-resistant mosquitoes (P = 0.210). Based on these findings, NIRS chronological age estimation technique for Anopheles mosquitoes may be independent of insecticide exposure and the environmental conditions to which the mosquitoes are exposed.
Cisplatin is widely used in the treatment of many tumors,particularly in ovarian cancer.GST-π,metallothionein(MT), multidrug resistance associated proteins(MRPs), nucleotide excision repair(NER), mismatch repair(MMR) and oncogenes contribute to drug resistance of cisplatin.
Full Text Available The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens.
刘斯璐; 崔峰; 燕帅国; 乔传令
蚊虫由于其特殊的行为、生理以及与人类生活关系紧密而成为传播人类疾病的重要媒介,自20世纪化学杀虫剂广泛使用后,蚊虫就与这种环境变化协同进化,即通过生理生化多种机制产生抗药性.该文综述了自90年代以来,我国7种媒介蚊虫尖音库蚊复组、中华按蚊、三带喙库蚊、微小按蚊、雷氏按蚊、白纹伊蚊和埃及伊蚊对有机磷类和拟除虫菊酯类杀虫剂的抗性调查结果.这些媒介蚊虫对两类杀虫剂均产生了一定程度的抗药性.对有机磷类杀虫剂进行抗性检测比较多的农药是马拉硫磷和敌敌畏,只有少数地区表现为敏感,大部分地区的蚊虫对其表现出不同程度的抗性.拟除虫菊酯类杀虫剂是近年使用最广泛的杀虫剂,大部分检测地区的蚊虫对该类杀虫剂也表现出不同程度的抗性.%Mosquitoes, due to their special behavior, physiology and close relationship with human beings, act as important vectors of some human diseases. The resistance of mosquitoes to insecticides is considered to be a recent evolutionary adaptation to environmental changes in response to the use of chemical insecticides. In this review we summarize the resistance monitor data on organophosphate and pyrethroid resistance in seven mosquito species in China (Culex pipiens complex, Anopheles sinensis, Cx. tritaeniorhynchus, An. minimus, An. lesteri, Aedes albopictus and Ae. aegypti) since 1990s. The documents showed that these mosquitoes in most regions of China have evolved to be resistant at various levels to organophosphate and pyrethroid insecticides, even though some of them still keep sensitive to the two kinds of insecticides.
Ricardo Alcántara-de la Cruz
Full Text Available Leptochloa virgata (L. P. Beauv. is an annual weed common in citrus groves in the states of Puebla and Veracruz, Mexico limiting their production. Since 2010, several L. virgata populations were identified as being resistant to glyphosate, but studies of their resistance mechanisms developed by this species have been conducted. In this work, three glyphosate-resistant populations (R8, R14 and R15 collected in citrus orchards from Mexico, were used to study their resistance mechanisms comparing them to one susceptible population (S. Dose-response and shikimic acid accumulation assays confirmed the glyphosate resistance of the three resistant populations. Higher doses of up to 720 g ae ha-1 (field dose were needed to control by 50% plants of resistant populations. The S population absorbed between 7 and 13% more 14C-glyphosate than resistant ones, and translocated up to 32.2% of 14C-glyphosate to the roots at 96 h after treatment (HAT. The R8, R14 and R15 populations translocated only 24.5, 26.5 and 21.9%, respectively. The enzyme activity of 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS was not different in the S, R8 and R14 populations. The R15 Population exhibited 165.9 times greater EPSPS activity. Additionally, this population showed a higher EPSPS basal activity and a substitution in the codon 106 from Proline to Serine in the EPSPS protein sequence. EPSPS gene expression in the R15 population was similar to that of S population. In conclusion, the three resistant L. virgata populations show reduced absorption and translocation of 14C-glyphosate. Moreover, a mutation and an enhanced EPSPS basal activity at target-site level confers higher resistance to glyphosate. These results describe for the first time the glyphosate resistance mechanisms developed by resistant L. virgata populations of citrus orchards from Mexico.
Alcántara-de la Cruz, Ricardo; Rojano-Delgado, Antonia M.; Giménez, María J.; Cruz-Hipolito, Hugo E.; Domínguez-Valenzuela, José A.; Barro, Francisco; De Prado, Rafael
Leptochloa virgata (L.) P. Beauv. is an annual weed common in citrus groves in the states of Puebla and Veracruz, Mexico limiting their production. Since 2010, several L. virgata populations were identified as being resistant to glyphosate, but studies of their resistance mechanisms developed by this species have been conducted. In this work, three glyphosate-resistant populations (R8, R14, and R15) collected in citrus orchards from Mexico, were used to study their resistance mechanisms comparing them to one susceptible population (S). Dose-response and shikimic acid accumulation assays confirmed the glyphosate resistance of the three resistant populations. Higher doses of up to 720 g ae ha-1 (field dose) were needed to control by 50% plants of resistant populations. The S population absorbed between 7 and 13% more 14C-glyphosate than resistant ones, and translocated up to 32.2% of 14C-glyphosate to the roots at 96 h after treatment (HAT). The R8, R14, and R15 populations translocated only 24.5, 26.5, and 21.9%, respectively. The enzyme activity of 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS) was not different in the S, R8 and R14 populations. The R15 Population exhibited 165.9 times greater EPSPS activity. Additionally, this population showed a higher EPSPS basal activity and a substitution in the codon 106 from Proline to Serine in the EPSPS protein sequence. EPSPS gene expression in the R15 population was similar to that of S population. In conclusion, the three resistant L. virgata populations show reduced absorption and translocation of 14C-glyphosate. Moreover, a mutation and an enhanced EPSPS basal activity at target-site level confers higher resistance to glyphosate. These results describe for the first time the glyphosate resistance mechanisms developed by resistant L. virgata populations of citrus orchards from Mexico. PMID:27917189
Ghannoum, Mahmoud A.; Rice, Louis B
The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antimicrobial resistance from different angles. Areas addressed include mechanisms underlying this resistance, improved methods to detect resistance when it occurs, alternate options for the treatment of infections caused by resistant organisms, and strategies to ...
Rosen, B P
Salts and organic derivatives of arsenic and antimony are quite toxic. Living organisms have adapted to this toxicity by the evolution of resistance mechanisms. Both prokaryotic and eukaryotic cells develop resistance when exposed to arsenicals or antimonials. In the case of bacteria resistance is conferred by plasmid-encoded arsenical resistance (ars) operons. The genes and gene products of the ars operon of the clinically-isolated conjugative R-factor R773 have been identified and their mechanism of action elucidated. The operon encodes an ATP-driven pump that extrudes arsenite and antimonite from the cells. The lowering of their intracellular concentration results in resistance. Arsenate resistance results from the action of the plasmid-encoded arsenate reductase that reduces arsenate to arsenite, which is then pumped out of the cell.
Maestre-Serrano, Ronald; Gomez-Camargo, Doris; Ponce-Garcia, Gustavo; Flores, Adriana E
We determined the susceptibility to insecticides and the biochemical and molecular mechanisms involved in resistance in nine populations of Aedes aegypti (L.) of the Colombian Caribbean region. Bioassays were performed on larvae for susceptibility to temephos and on adults to the insecticides malathion, fenitrothion, pirimiphos-methyl, permethrin, deltamethrin, λ-cyhalothrin and cyfluthrin. The resistance ratio (RR) for each insecticide in the populations was determined, using the susceptible Rockefeller strain as a susceptible control. Additionally, we evaluated the response of the populations to the diagnostic dose (DD) of the organochlorine pesticide DDT. The following biochemical mechanisms associated with resistance were studied: α-esterases, β-esterases, mixed-function oxidases (MFO), glutathione s-transferases (GST) and insensitive acetylcholinesterase (iAChE) as well as the presence of kdr I1,016 mutation and its frequency. All populations studied showed susceptibility to the organophosphates evaluated (RR < 5-fold), except for the Puerto Colombia and Soledad populations which showed high resistance (RR 15-fold) and moderate resistance (RR 5-fold) to temephos, respectively, and Sincelejo (Sucre) with moderate resistance to pirimiphos-methyl (RR 5-fold). All populations evaluated with DD of DDT were found to be resistant with 2-28% of mortality. Variability was observed in the resistance to pyrethroids: permethrin (RR 1.2- to 30.8-fold), deltamethrin RR 0.9- to 37.8-fold), λ-cyalothrin (RR 3.4- to 83-fold) and cyfluthrin (RR 0.3- to 33.8-fold). Incipiently α-esterases and MFO levels were found in the Valledupar population; MFO showed the same profile in Cienaga and GST in the Sincelejo population, all other populations showed unaltered profiles of the enzymes evaluated. The kdr I1,016 mutation was found in all populations evaluated with variability in its allelic and genotypic frequencies.
Hu, Zhaonong; Du, Yuzhe; Nomura, Yoshiko; Dong, Ke
Voltage-gated sodium channels are the primary target of pyrethroid insecticides. Numerous point mutations in sodium channel genes have been identified in pyrethroid-resistant insect species, and many have been confirmed to reduce or abolish sensitivity of channels expressed in Xenopus oocytes to pyrethroids. Recently, several novel mutations were reported in sodium channel genes of pyrethroid-resistant Aedes mosquito populations. One of the mutations is a phenylalanine (F) to cysteine (C) change in segment 6 of domain III (IIIS6) of the Aedes mosquito sodium channel. Curiously, a previous study showed that alanine substitution of this F did not alter the action of deltamethrin, a type II pyrethroid, on a cockroach sodium channel. In this study, we changed this F to C in a pyrethroid-sensitive cockroach sodium channel and examined mutant channel sensitivity to permethrin as well as five other type I or type II pyrethroids in Xenopus oocytes. Interestingly, the F to C mutation drastically reduced channel sensitivity to three type I pyrethroids, permethrin, NRDC 157 (a deltamethrin analogue lacking the α-cyano group) and bioresemthrin, but not to three type II pyrethroids, cypermethrin, deltamethrin and cyhalothrin. These results confirm the involvement of the F to C mutation in permethrin resistance, and raise the possibility that rotation of type I and type II pyrethroids might be considered in the control of insect pest populations where this particular mutation is present.
Maund, S J; Campbell, P J; Giddings, J M; Hamer, M J; Henry, K; Pilling, E D; Warinton, J S; Wheeler, J R
In this chapter we review the ecotoxicology of the synthetic pyrethroids (SPs). SPs are potent, broad-spectrum insecticides. Their effects on a wide range of nontarget species have been broadly studied, and there is an extensive database available to evaluate their effects. SPs are highly toxic to fish and aquatic invertebrates in the laboratory, but effects in the field are mitigated by rapid dissipation and degradation. Due to their highly lipophilic nature, SPs partition extensively into sediments. Recent studies have shown that toxicity in sediment can be predicted on the basis of equilibrium partitioning, and whilst other factors can influence this, organic carbon content is a key determining variable. At present for SPs, there is no clear evidence for adverse population-relevant effects with an underlying endocrine mode of action. SPs have been studied intensively in aquatic field studies, and their effects under field conditions are mitigated from those measured in the laboratory by their rapid dissipation and degradation. Studies with a range of test systems have shown consistent aquatic field endpoints across a variety of geographies and trophic states. SPs are also highly toxic to bees and other nontarget arthropods in the laboratory. These effects are mitigated in the field through repellency and dissipation of residues, and recovery from any adverse effects tends to be rapid.
Rinkevich, Frank D; Du, Yuzhe; Tolinski, Josh; Ueda, Atsushi; Wu, Chun-Fang; Zhorov, Boris S; Dong, Ke
Voltage-gated sodium channels (Nav channels) are critical for electrical signaling in the nervous system and are the primary targets of the insecticides DDT and pyrethroids. In Drosophila melanogaster, besides the canonical Nav channel, Para (also called DmNav), there is a sodium channel-like cation channel called DSC1 (Drosophila sodium channel 1). Temperature-sensitive paralytic mutations in DmNav (para(ts)) confer resistance to DDT and pyrethroids, whereas DSC1 knockout flies exhibit enhanced sensitivity to pyrethroids. To further define the roles and interaction of DmNav and DSC1 channels in DDT and pyrethroid neurotoxicology, we generated a DmNav/DSC1 double mutant line by introducing a para(ts1) allele (carrying the I265N mutation) into a DSC1 knockout line. We confirmed that the I265N mutation reduced the sensitivity to two pyrethroids, permethrin and deltamethrin of a DmNav variant expressed in Xenopus oocytes. Computer modeling predicts that the I265N mutation confers pyrethroid resistance by allosterically altering the second pyrethroid receptor site on the DmNav channel. Furthermore, we found that I265N-mediated pyrethroid resistance in para(ts1) mutant flies was almost completely abolished in para(ts1);DSC1(-/-) double mutant flies. Unexpectedly, however, the DSC1 knockout flies were less sensitive to DDT, compared to the control flies (w(1118A)), and the para(ts1);DSC1(-/-) double mutant flies were even more resistant to DDT compared to the DSC1 knockout or para(ts1) mutant. Our findings revealed distinct roles of the DmNav and DSC1 channels in the neurotoxicology of DDT vs. pyrethroids and implicate the exciting possibility of using DSC1 channel blockers or modifiers in the management of pyrethroid resistance.
Yujiao, Zhang; Xiaojing, Li; Kaixia, Mi
Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is one of the world's deadliest bacterial infectious disease. It is still a global-health threat, particularly because of the drug-resistant forms. Fluoroquinolones, with target of gyrase, are among the drugs used to treat tuberculosis. However, their widespread use has led to bacterial resistance. The molecular mechanisms of fluoroquinolone resistance in mycobacterium tuberculosis have been reported, such as DNA gyrase mutations, drug efflux pumps system, bacterial cell wall thickness and pentapeptide proteins (MfpA) mediated regulation of gyrase. Mutations in gyrase conferring quinolone resistance play important roles and have been extensively studied. Recent studies have shown that the regulation of DNA gyrase affects mycobacterial drug resistance, but the mechanisms, especially by post-translational modification and regulatory proteins, are poorly understood. In this review, we summarize the fluoroquinolone drug development, and the molecular genetics of fluoroquinolone resistance in mycobacteria. Comprehensive understanding of the mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis will open a new view on understanding drug resistance in mycobacteria and lead to novel strategies to develop new accurate diagnosis methods.
Miller, William R; Munita, Jose M; Arias, Cesar A
Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches. PMID:25199988
Miller, William R; Munita, Jose M; Arias, Cesar A
Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches.
Taff, Heather T; Mitchell, Kaitlin F; Edward, Jessica A; Andes, David R
Candida commonly adheres to implanted medical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. As currently available antifungals have minimal activity against biofilms, new drugs to treat these recalcitrant infections are urgently needed. Recent investigations have begun to shed light on the mechanisms behind the profound resistance associated with the biofilm mode of growth. This resistance appears to be multifactorial, involving both mechanisms similar to conventional, planktonic antifungal resistance, such as increased efflux pump activity, as well as mechanisms specific to the biofilm lifestyle. A unique biofilm property is the production of an extracellular matrix. Two components of this material, β-glucan and extracellular DNA, promote biofilm resistance to multiple antifungals. Biofilm formation also engages several stress response pathways that impair the activity of azole drugs. Resistance within a biofilm is often heterogeneous, with the development of a subpopulation of resistant persister cells. In this article we review the molecular mechanisms underlying Candida biofilm antifungal resistance and their relative contributions during various growth phases. PMID:24059922
Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659
Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy.
Casas, Adriana; Di Venosa, Gabriela; Hasan, Tayyaba; Batlle, Alcira
Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by illumination with visible light, leading to generation of reactive oxygen species. The mechanisms of resistance to PDT ascribed to the PS may be shared with the general mechanisms of drug resistance, and are related to altered drug uptake and efflux rates or altered intracellular trafficking. As a second step, an increased inactivation of oxygen reactive species is also associated to PDT resistance via antioxidant detoxifying enzymes and activation of heat shock proteins. Induction of stress response genes also occurs after PDT, resulting in modulation of proliferation, cell detachment and inducing survival pathways among other multiple extracellular signalling events. In addition, an increased repair of induced damage to proteins, membranes and occasionally to DNA may happen. PDT-induced tissue hypoxia as a result of vascular damage and photochemical oxygen consumption may also contribute to the appearance of resistant cells. The structure of the PS is believed to be a key point in the development of resistance, being probably related to its particular subcellular localization. Although most of the features have already been described for chemoresistance, in many cases, no cross-resistance between PDT and chemotherapy has been reported. These findings are in line with the enhancement of PDT efficacy by combination with chemotherapy. The study of cross resistance in cells with developed resistance against a particular PS challenged against other PS is also highly complex and comprises different mechanisms. In this review we will classify the different features observed in PDT resistance, leading to a comparison with the mechanisms most commonly found in chemo resistant cells. PMID:21568910
Flores, Adriana E; Grajales, Jaime Salomon; Salas, Ildefonso Fernandez; Garcia, Gustavo Ponce; Becerra, Ma Haydee Loaiza; Lozano, Saul; Brogdon, William G; Black, William C; Beaty, Barry
Potential insecticide-resistance mechanisms were studied with the use of biochemical assays in Aedes aegypti (L.) collected from 5 municipalities representing the north part of Quintana Roo: Benito Juarez, Cozumel, Isla Mujeres, Lazaro Cardenas, and Solidaridad. The activities of alpha and beta esterases, mixed-function oxidases (MFO), glutathione-S-transferase (GST), acethylcholinesterase (AChE), and insensitive acethylcholinesterase (iAChE) were assayed in microplates. Three replicates were performed for each enzyme and 60 males and 60 females were analyzed in each population. The New Orleans (NO) susceptible strain of Ae. aegypti was used as a susceptible reference and the threshold criteria for each enzyme were the highest NO absorbance values. In none of the 6 tests were absorbance values correlated in males and females. alpha esterases were elevated in Benito Juarez, Cozumel females and in Lazaro Cardenas males and females. beta esterases were elevated in Benito Juarez, Cozumel females and in Cozumel and Lazaro Cardenas males. Elevated esterases suggest potential insecticide-resistance mechanisms against organophosphate, carbamate, and some pyrethroid insecticides. Slightly elevated levels of MFOs appeared in Lazaro Cardenas females and in Cozumel, Isla Mujeres, and Solidaridad males. Mechanisms involving iAChE or GST were not apparent.
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Abiola Olumuyiwa Olaitan
Full Text Available Polymyxins are polycationic antimicrobial peptides that are currently the last-resort antibiotics for the treatment of multidrug-resistant, Gram-negative bacterial infections. The reintroduction of polymyxins for antimicrobial therapy has been followed by an increase in reports of resistance among Gram-negative bacteria. Some bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, develop resistance to polymyxins in a process referred to as acquired resistance, whereas other bacteria, such as Proteus spp., Serratia spp. and Burkholderia spp., are naturally resistant to these drugs. Reports of polymyxin resistance in clinical isolates have recently increased, including acquired and intrinsically resistant pathogens. This increase is considered a serious issue, prompting concern due to the low number of currently available effective antibiotics. This review summarizes current knowledge concerning the different strategies bacteria employ to resist the activities of polymyxins.Gram-negative bacteria employ several strategies to protect themselves from polymyxin antibiotics (polymyxin B and colistin, including a variety of lipopolysaccharide (LPS modifications, such as modifications of lipid A with phosphoethanolamine and 4-amino-4-deoxy-L-arabinose, in addition to the use of efflux pumps, the formation of capsules and overexpression of the outer membrane protein OprH, which are all effectively regulated at the molecular level. The increased understanding of these mechanisms is extremely vital and timely to facilitate studies of antimicrobial peptides and find new potential drugs targeting clinically relevant Gram-negative bacteria.
Evaluation of efficacy of Interceptor(®) G2, a long-lasting insecticide net coated with a mixture of chlorfenapyr and alpha-cypermethrin, against pyrethroid resistant Anopheles gambiae s.l. in Burkina Faso.
Bayili, Koama; N'do, Severin; Namountougou, Moussa; Sanou, Roger; Ouattara, Abdoulaye; Dabiré, Roch K; Ouédraogo, Anicet G; Malone, David; Diabaté, Abdoulaye
Malaria vectors have acquired widespread resistance throughout sub-Saharan Africa to many of the currently used insecticides. Hence, there is an urgent need to develop alternative strategies including the development of new insecticides for effective management of insecticide resistance. To maintain progress against malaria, it is necessary to identify other residual insecticides for mosquito nets. In the present WHOPES phase II analogue study, the utility of chlorfenapyr, a pyrrole class insecticide mixed with alpha-cypermethrin on a long-lasting mosquito bed net was evaluated against Anopheles gambiae s.l. Bed nets treated with chlorfenapyr and alpha-cypermethrin and mixture of both compounds were tested for their efficacy on mosquitoes. Washed (20 times) and unwashed of each type of treated nets and were tested according to WHOPES guidelines. Efficacy of nets were expressed in terms of blood-feeding inhibition rate, deterrence, induced exophily and mortality rate. The evaluation was conducted in experimental huts of Vallée du Kou seven (VK7) in Burkina Faso (West Africa) following WHOPES phase II guidelines. In addition, a WHOPES phase I evaluation was also performed. Mixture treated nets killed significantly (P 0.05) different from nets treated with chlorfenapyr 200 mg/m(2) unwashed (86%). The washed and unwashed nets treated with the mixtures resulted in personal protection against An. gambiae s.l. biting 34 and 44%. In contrast the personal protection observed for washed and unwashed alpha-cypermethrin treated nets generated (14 and 24%), and chlorfenapyr solo treated net was rather low (22%). Among all nets trialled, the combination of chlorfenapyr and alpha-cypermethrin on bed nets provided better mortality in phase II after 20 washes. Results suggest that this combination could be a potential insecticide resistance management tool for preventing malaria transmission in areas compromised by the spread of pyrethroid resistance.
Johnson, Reed M; Wen, Zhimou; Schuler, Mary A; Berenbaum, May R
Honey bees, Apis mellifera L., often thought to be extremely susceptible to insecticides in general, exhibit considerable variation in tolerance to pyrethroid insecticides. Although some pyrethroids, such as cyfluthrin and lambda-cyhalothrin, are highly toxic to honey bees, the toxicity of tau-fluvalinate is low enough to warrant its use to control parasitic mites inside honey bee colonies. Metabolic insecticide resistance in other insects is mediated by three major groups of detoxifying enzymes: the cytochrome P450 monooxygenases (P450s), the carboxylesterases (COEs), and the glutathione S-transferases (GSTs). To test the role of metabolic detoxification in mediating the relatively low toxicity of tau-fluvalinate compared with more toxic pyrethroid insecticides, we examined the effects of piperonyl butoxide (PBO), S,S,S-tributylphosphorotrithioate (DEF), and diethyl maleate (DEM) on the toxicity of these pyrethroids. The toxicity of the three pyrethroids to bees was greatly synergized by the P450 inhibitor PBO and synergized at low levels by the carboxylesterase inhibitor DEF. Little synergism was observed with DEM. These results suggest that metabolic detoxification, especially that mediated by P450s, contributes significantly to honey bee tolerance of pyrethroid insecticides. The potent synergism between tau-fluvalinate and PBO suggests that P450s are especially important in the detoxification of this pyrethroid and explains the ability of honey bees to tolerate its presence.
Pan, Shu-Ting; Li, Zhi-Ling; He, Zhi-Xu; Qiu, Jia-Xuan; Zhou, Shu-Feng
Chemotherapy is one of the prevailing methods used to treat malignant tumours, but the outcome and prognosis of tumour patients are not optimistic. Cancer cells gradually generate resistance to almost all chemotherapeutic drugs via a variety of distinct mechanisms and pathways. Chemotherapeutic resistance, either intrinsic or acquired, is caused and sustained by reduced drug accumulation and increased drug export, alterations in drug targets and signalling transduction molecules, increased repair of drug-induced DNA damage, and evasion of apoptosis. In order to better understand the mechanisms of chemoresistance, this review highlights our current knowledge of the role of altered drug metabolism and transport and deregulation of apoptosis and autophagy in the development of tumour chemoresistance. Reduced intracellular activation of prodrugs (e.g. thiotepa and tegafur) or enhanced drug inactivation by Phase I and II enzymes contributes to the development of chemoresistance. Both primary and acquired resistance can be caused by alterations in the transport of anticancer drugs which is mediated by a variety of drug transporters such as P-glycoprotein (P-gp), multidrug resistance associated proteins, and breast cancer resistance protein. Presently there is a line of evidence indicating that deregulation of programmed cell death including apoptosis and autophagy is also an important mechanism for tumour resistance to anticancer drugs. Reversal of chemoresistance is likely via pharmacological and biological approaches. Further studies are warranted to grasp the full picture of how each type of cancer cells develop resistance to anticancer drugs and to identify novel strategies to overcome it.
Hawkes, Timothy R
The aim of this brief review is to draw information from studies of the mechanism of evolved resistance in weeds, together with information from laboratory studies of paraquat tolerance in model plants. Plants having mutations that limit paraquat uptake into cytoplasm, that confer various stress tolerances or that have transgenes that co-express two or more of the chloroplast Halliwell-Asada cycle enzymes can all exhibit enhanced tolerance to paraquat. However, none of these mechanisms correspond to the high-level resistances that have evolved naturally in weeds. Most, but not all, of the evidence from studies of paraquat-resistant biotypes of weeds can reasonably be reconciled with the proposal of a single major gene mechanism that sequesters paraquat away from chloroplasts and into the vacuole. However, the molecular details of this putative mechanism remain ill-defined.
Ghannoum, M A; Rice, L B
The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antimicrobial resistance from different angles. Areas addressed include mechanisms underlying this resistance, improved methods to detect resistance when it occurs, alternate options for the treatment of infections caused by resistant organisms, and strategies to prevent and control the emergence and spread of resistance. In this review, the mode of action of antifungals and their mechanisms of resistance are discussed. Additionally, an attempt is made to discuss the correlation between fungal and bacterial resistance. Antifungals can be grouped into three classes based on their site of action: azoles, which inhibit the synthesis of ergosterol (the main fungal sterol); polyenes, which interact with fungal membrane sterols physicochemically; and 5-fluorocytosine, which inhibits macromolecular synthesis. Many different types of mechanisms contribute to the development of resistance to antifungals. These mechanisms include alteration in drug target, alteration in sterol biosynthesis, reduction in the intercellular concentration of target enzyme, and overexpression of the antifungal drug target. Although the comparison between the mechanisms of resistance to antifungals and antibacterials is necessarily limited by several factors defined in the review, a correlation between the two exists. For example, modification of enzymes which serve as targets for antimicrobial action and the involvement of membrane pumps in the extrusion of drugs are well characterized in both the eukaryotic and prokaryotic cells.
Felix David Guerrero
Full Text Available Acaricide resistance has become widespread in countries where cattle ticks, Rhipicephalus (Boophilus microplus, are a problem. Resistance arises through genetic changes in a cattle tick population that causes modifications to the target site, increased metabolism or sequestration of the acaricide, or reduced ability of the acaricide to penetrate through the outer protective layers of the tick’s body. We review the molecular and biochemical mechanisms of acaricide resistance that have been shown to be functional in R. (B. microplus. From a mechanistic point of view, resistance to pyrethroids has been characterized to a greater degree than any other acaricide class. Although a great deal of research has gone into discovery of the mechanisms that cause organophosphate resistance, very little is defined at the molecular level and organophosphate resistance seems to be maintained through a complex and multifactorial process. The resistance mechanisms for other acaricides are less well understood. The target sites of fipronil and the macrocyclic lactones are known and resistance mechanism studies are in the early stages. The target site of amitraz has not been definitively identified and this is hampering mechanistic studies on this acaricide.A resistência aos acaricidas tornou-se amplamente difundida nos países onde os carrapatos bovinos, Rhipicephalus .Boophilus. microplus, são um problema. A resistência surge por meio de alterações genéticas em umapopulação de carrapatos que causam modificações no local de ação, aumento do metabolismo ou sequestro do acaricida, ou ainda redução na capacidade do acaricida em penetrar através das camadas protetoras do corpo do carrapato. Neste artigo, foram revisados os mecanismos moleculares e bioquímicos da resistência aos acaricidas que ocorrem em R. (B. microplus. A partir de um ponto de vista dos mecanismos envolvidos, a resistência aos piretróides tem sido caracterizada em maior grau do
Vranakis, Iosif; Goniotakis, Ioannis; Psaroulaki, Anna; Sandalakis, Vassilios; Tselentis, Yannis; Gevaert, Kris; Tsiotis, Georgios
Ever since antibiotics were used to help humanity battle infectious diseases, microorganisms straight away fought back. Antibiotic resistance mechanisms indeed provide microbes with possibilities to by-pass and survive the action of antibiotic drugs. Several methods have been employed to identify these microbial resistance mechanisms in an ongoing effort to reduce the steadily increasing number of treatment failures due to multi-drug-resistant microbes. Proteomics has evolved to an important tool for this area of research. Following rapid advances in whole genome sequencing, proteomic technologies have been widely used to investigate microbial gene expression. This review highlights the contribution of proteomics in identifying microbial drug resistance mechanisms. It summarizes different proteomic studies on bacteria resistant to different antibiotic drugs. The review further includes an overview of the methodologies used, as well as lists key proteins identified, thus providing the reader not only a summary of research already done, but also directions for future research. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.
Gillet, Jean-Pierre; Gottesman, Michael M
The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by numerous mechanisms including decreased drug uptake, increased drug efflux, activation of detoxifying systems, activation of DNA repair mechanisms, evasion of drug-induced apoptosis, etc. In the first part of this chapter, we briefly summarize the current knowledge on individual cellular mechanisms responsible for MDR, with a special emphasis on ATP-binding cassette transporters, perhaps the main theme of this textbook. Although extensive work has been done to characterize MDR mechanisms in vitro, the translation of this knowledge to the clinic has not been crowned with success. Therefore, identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing clinical samples could help to predict the development of resistance and lead to treatments designed to circumvent it. Our thoughts about translational research needed to achieve significant progress in the understanding of this complex phenomenon are therefore discussed in a third section. The pleotropic response of cancer cells to chemotherapy is summarized in a concluding diagram.
Kawada, Hitoshi; Higa, Yukiko; Nguyen, Yen T; Tran, Son H; Nguyen, Hoa T; Takagi, Masahiro
Pyrethroid resistance is envisioned to be a major problem for the vector control program since, at present, there are no suitable chemical substitutes for pyrethroids. Cross-resistance to knockdown agents, which are mainly used in mosquito coils and related products as spatial repellents, is the most serious concern. Since cross-resistance is a global phenomenon, we have started to monitor the distribution of mosquito resistance to pyrethroids. The first pilot study was carried out in Vietnam. We periodically drove along the national road from the north end to the Mekong Delta in Vietnam and collected mosquito larvae from used tires. Simplified susceptibility tests were performed using the fourth instar larvae of Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus. Compared with the other species, Ae. aegypti demonstrated the most prominent reduction in susceptibility. For Ae. aegypti, significant increases in the susceptibility indices with a decrease in the latitude of collection points were observed, indicating that the susceptibility of Ae. aegypti against d-allethrin was lower in the southern part, including mountainous areas, as compared to that in the northern part of Vietnam. There was a significant correlation between the susceptibility indices in Ae. aegypti and the sum of annual pyrethroid use for malaria control (1998-2002). This might explain that the use of pyrethroids as residual treatment inside houses and pyrethroid-impregnated bed nets for malaria control is attributable to low pyrethroid susceptibility in Ae. aegypti. Such insecticide treatment appeared to have been intensively administered in the interior and along the periphery of human habitation areas where, incidentally, the breeding and resting sites of Ae. aegypti are located. This might account for the strong selection pressure toward Ae. aegypti and not Ae. albopictus.
Álvarez-Hernández, Diego Abelardo; Garza-Mayén, Gilda Sofía; Vázquez-López, Rosalno
Quinolones are a family of synthetic broad-spectrum antimicrobial drugs whose target is the synthesis of DNA. They directly inhibit DNA replication by interacting with two enzymes; DNA gyrase and topoisomerase IV. They have been widely used for the treatment of several community and hospital acquired infections, in the food processing industry and in the agricultural field, making the increasing incidence of quinolone resistance a frequent problem associated with constant exposition to diverse microorganisms. Resistance may be achieved by three non-exclusive mechanisms; through chromosomic mutations in the Quinolone Resistance-Determining Regions of DNA gyrase and topoisomerase IV, by reducing the intracytoplasmic concentrations of quinolones actively or passively and by Plasmid-Mediated Quinolones-Resistance genes, [Qnr determinant genes of resistance to quinolones, variant gene of the aminoglycoside acetyltransferase (AAC(6')-Ib-c)] and encoding genes of efflux pumps (qepA and oqxAB)]. The future of quinolones is uncertain, however, meanwhile they continue to be used in an irrational way, increasing resistance to quinolones should remain as an area of primary priority for research.
Mogensen, B. B.; Sørensen, P. B.; Stuer-Lauridsen, F.;
Pyrethroids constitute a group of widely used insecticides, which are toxic to aquatic organisms. This report presents the results from a 2-year study of the fate of pyrethroids in ponds, i.e. their distribution in the water column, the sediment and the surface microlayer respectively. The measur......Pyrethroids constitute a group of widely used insecticides, which are toxic to aquatic organisms. This report presents the results from a 2-year study of the fate of pyrethroids in ponds, i.e. their distribution in the water column, the sediment and the surface microlayer respectively...
Improved understanding of the factors determining the insecticidal activity, the mammalian toxicity, and the stability in air and light of natural and synthetic pyrethroids has led to a series of new compounds with a very favorable combination of properties. Their characteristics include outstanding potency to insects, low toxicity to mammals associated with rapid metabolic breakdown and, in appropriate cases, adequate stability on plant surfaces even in bright sunlight. Initial tests indicate that even the more stable compounds are degraded rapidly in soil, so if the trials at present in progress reveal no toxicological or environmental hazards, within a few years synthetic pyrethroids should be available to control a wide range of domestic, veterinary, horticultural, agricultural, and forest pests at low rates of application.
Aldred, Katie J; Kerns, Robert J; Osheroff, Neil
Quinolones are one of the most commonly prescribed classes of antibacterials in the world and are used to treat a variety of bacterial infections in humans. Because of the wide use (and overuse) of these drugs, the number of quinolone-resistant bacterial strains has been growing steadily since the 1990s. As is the case with other antibacterial agents, the rise in quinolone resistance threatens the clinical utility of this important drug class. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome. This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quinolone action against their enzyme targets. It will then discuss the following three mechanisms that decrease the sensitivity of bacterial cells to quinolones. Target-mediated resistance is the most common and clinically significant form of resistance. It is caused by specific mutations in gyrase and topoisomerase IV that weaken interactions between quinolones and these enzymes. Plasmid-mediated resistance results from extrachromosomal elements that encode proteins that disrupt quinolone-enzyme interactions, alter drug metabolism, or increase quinolone efflux. Chromosome-mediated resistance results from the underexpression of porins or the overexpression of cellular efflux pumps, both of which decrease cellular concentrations of quinolones. Finally, this review will discuss recent advancements in our understanding of how quinolones interact with gyrase and topoisomerase IV and how mutations in these enzymes cause resistance. These last findings suggest approaches to designing new drugs that display improved activity against resistant strains.
Karunaratne SHP Parakrama
Full Text Available Abstract Background The current status of insecticide resistance and the underlying resistance mechanisms were studied in the major vector of malaria, Anopheles culicifacies, and the secondary vector, Anopheles subpictus in five districts (Anuradhapura, Kurunegala, Moneragala, Puttalam and Trincomalee of Sri Lanka. Eight other anophelines, Anopheles annularis, Anopheles barbirostris, Anopheles jamesii, Anopheles nigerrimus, Anopheles peditaeniatus, Anopheles tessellatus, Anopheles vagus and Anopheles varuna from Anuradhapura district were also tested. Methods Adult females were exposed to the WHO discriminating dosages of DDT, malathion, fenitrothion, propoxur, λ-cyhalothrin, cyfluthrin, cypermethrin, deltamethrin, permethrin and etofenprox. The presence of metabolic resistance by esterase, glutathione S-transferase (GST and monooxygenase-based mechanisms, and the sensitivity of the acetylcholinesterase target site were assessed using synergists, and biochemical, and metabolic techniques. Results All the anopheline species had high DDT resistance. All An. culicifacies and An. subpictus populations were resistant to malathion, except An. culicifacies from Kurunegala, where there was no malathion carboxylesterase activity. Kurunegala and Puttalam populations of An. culicifacies were susceptible to fenitrothion. All the An. culicifacies populations were susceptible to carbamates. Both species were susceptible to the discriminating dosages of cypermethrin and cyfluthrin, but had different levels of resistance to other pyrethroids. Of the 8 other anophelines, only An. nigerrimus and An. peditaeniatus were resistant to all the insecticides tested, probably due to their high exposure to the insecticides used in agriculture. An. vagus showed some resistance to permethrin. Esterases, GSTs and monooxygenases were elevated in both An. culicifacies and An. subpictus. AChE was most sensitive to insecticides in Kurunegala and Trincomalee An. culicifacies
Yulian P. Ramirez
Full Text Available Glioblastoma multiforme (GBM is a grade IV brain tumor characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy. The current standard of care, comprised of surgical resection followed by radiation and the chemotherapeutic agent temozolomide, only provides patients with a 12–14 month survival period post-diagnosis. Long-term survival for GBM patients remains uncommon as cells with intrinsic or acquired resistance to treatment repopulate the tumor. In this review we will describe the mechanisms of resistance, and how they may be overcome to improve the survival of GBM patients by implementing novel chemotherapy drugs, new drug combinations and new approaches relating to DNA damage, angiogenesis and autophagy.
M. R. Chorawala
Full Text Available The management of cancer involves surgery, radiotherapy and chemotherapy. Development of chemoresistance is a persistent problem during the chemotherapy treatment. Cytotoxic drugs that selectively, but not exclusively, target actively proliferating cells include such diverse groups as DNA-alkylating agents, anti-metabolites, intercalating agents and mitotic inhibitors. Resistance constitutes a lack of response to drug-induced tumour growth inhibition; it may be inherent in a subpopulation of heterogeneous cancer cells or be acquired as a cellular response to drug exposure. Principle mechanisms may include altered membrane transport involving the p-glycoprotein product of the multidrug resistance (MDR gene as well as other associated proteins, altered target enzyme, decreased drug activation, increased drug degradation due to altered expression of drug metabolising enzymes, drug inactivation due to conjugation with increased glutathione, subcellular redistribution, drug interaction, enhanced DNA repair and failure to apoptosis as a result of mutated cell cycle proteins such as p53. Attempts to overcome resistance involves the use of combination drug therapy using different classes of drugs with minimally overlapping toxicities to allow maximal dosages, necessary for bone marrow recovery. Adjuvant therapy with p-glycoprotein inhibitors and in speciﬁc instances, the use of growth factor and protein kinase C inhibitors are newer experimental approaches that may also prove effective in delaying onset of resistance. Gene knockout using antisense molecules may be effective way of blocking drug resistance.
The common bed bug, Cimex lectularius (L.) (Hemiptera: Cimicidae) is undergoing a rapid resurgence in the United States during the last decade which has created a notable pest management challenge largely because the pest has developed resistance against DDT, organophosphates, carbamates, and pyreth...
Rhipicephalus microplus is an invasive tick vector that transmits the protozoan parasites Babesia bovis and B. bigemina, the causative agents of bovine babesiosis (cattle fever). Acaricide resistant R. microplus populations have become a major problem for many cattle producing areas of the world. Py...
OCHOMO, E.; BAYOH, M. N.; BROGDON, W. G.; GIMNIG, J. E.; OUMA, C.; VULULE, J. M.; WALKER, E. D.
Field and laboratory investigations revealed phenotypic, target site and metabolic resistance to permethrin in an Anopheles gambiae s.s. (Diptera: Culicidae) population in Bungoma District, a region in western Kenya in which malaria is endemic and rates of ownership of insecticide-treated bednets are high. The sensitivity of individual An. gambiae s.l. females as indicated in assays using World Health Organization (WHO) test kits demonstrated reduced mortality in response to permethrin, deltamethrin and bendiocarb. Estimated time to knock-down of 50% (KDT50) of the test population in Centers for Disease Control (CDC) bottle bioassays was significantly lengthened for the three insecticides compared with that in a susceptible control strain. Anopheles arabiensis from all three sites showed higher mortality to all three insecticides in the WHO susceptibility assays compared with the CDC bottle assays, in which they showed less sensitivity and longer KDT50 than the reference strain for permethrin and deltamethrin. Microplate assays revealed elevated activity of β-esterases and oxidases, but not glutathione-S-transferase, in An. gambiae s.s. survivors exposed to permethrin in bottle bioassays compared with knocked down and unexposed individuals. No An. arabiensis showed elevated enzyme activity. The 1014S kdr allele was fixed in the Bungoma An. gambiae s.s. population and absent from An. arabiensis, whereas the 1014F kdr allele was absent from all samples of both species. Insecticide resistance could compromise vector control in Bungoma and could spread to other areas as coverage with longlasting insecticide-treated bednets increases. PMID:22861380
Ramírez-Díaz, Martha I; Díaz-Pérez, César; Vargas, Eréndira; Riveros-Rosas, Héctor; Campos-García, Jesús; Cervantes, Carlos
Chromium is a non-essential and well-known toxic metal for microorganisms and plants. The widespread industrial use of this heavy metal has caused it to be considered as a serious environmental pollutant. Chromium exists in nature as two main species, the trivalent form, Cr(III), which is relatively innocuous, and the hexavalent form, Cr(VI), considered a more toxic species. At the intracellular level, however, Cr(III) seems to be responsible for most toxic effects of chromium. Cr(VI) is usually present as the oxyanion chromate. Inhibition of sulfate membrane transport and oxidative damage to biomolecules are associated with the toxic effects of chromate in bacteria. Several bacterial mechanisms of resistance to chromate have been reported. The best characterized mechanisms comprise efflux of chromate ions from the cell cytoplasm and reduction of Cr(VI) to Cr(III). Chromate efflux by the ChrA transporter has been established in Pseudomonas aeruginosa and Cupriavidus metallidurans (formerly Alcaligenes eutrophus) and consists of an energy-dependent process driven by the membrane potential. The CHR protein family, which includes putative ChrA orthologs, currently contains about 135 sequences from all three domains of life. Chromate reduction is carried out by chromate reductases from diverse bacterial species generating Cr(III) that may be detoxified by other mechanisms. Most characterized enzymes belong to the widespread NAD(P)H-dependent flavoprotein family of reductases. Several examples of bacterial systems protecting from the oxidative stress caused by chromate have been described. Other mechanisms of bacterial resistance to chromate involve the expression of components of the machinery for repair of DNA damage, and systems related to the homeostasis of iron and sulfur.
Taylor, J S; Thomson, B M; Lang, C N; Sin, F Y T; Podivinsky, E
Studies suggested that exposure to agricultural pesticides may affect male fertility. Pyrethroids are widely used pesticides due to their insecticidal potency and low mammalian toxicity. A recombinant yeast assay system incorporating the human alpha-estrogen receptor was used to analyze the estrogenicity of a range of readily available pyrethroid pesticides. The commercial product Ripcord Plus showed estrogenic activity by this assay. To determine whether pyrethroid compounds might exert an effect on male fertility, mouse Sertoli cells were exposed in vitro to the endogenous estrogen, 17beta-estradiol, and selected estrogenic pyrethroids. Following exposure, transcript levels of the alpha- and beta-estrogen receptors were assessed. Exposure of Sertoli cells to the pyrethroid compounds, both at high and at low published serum concentrations, affected the expression of the two estrogen receptors; however, the influence on estrogen receptor gene expression was different from the effect from exposure to 17beta-estradiol. These results from our model systems suggest that (1) estrogenic pyrethroid pesticides affect the estrogen receptors, and therefore potentially the endocrine system, in a different manner from that of endogenous estrogen, and (2) should cells in the male testes be exposed to pyrethroid pesticides, male fertility may be affected through molecular mechanisms involving estrogen receptors.
Full Text Available Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Most of the probiotic bacteria currently available in the market belong to the genera Lactobacillus and Bifidobacterium, and specific health-promoting activities, such as treatment of diarrhea or amelioration of gastrointestinal discomfort, have been attributed to them. In order to be able to survive the gastrointestinal transit and transiently colonise our gut, these bacteria must be able to counteract the deleterious action of bile salts, which are the main components of bile. Bile salts are detergent-like biological substances synthesised in the liver from cholesterol. Host enzymes conjugate the newly synthesised free bile acids in the liver with the amino acids glycine or taurine, generating conjugated bile salts. These compounds are stored in the gall bladder and they are released into the duodenum during digestion to perform their physiological function, which is the solubilisation of fat coming from diet. These bile salts possess strong antimicrobial activity, since they are able to disorganize the structure of the cell membrane, as well as trigger DNA damage. This means that bacteria inhabiting our intestinal tract must have intrinsic resistance mechanisms to cope with bile salts. To do that, Lactobacillus and Bifidobacterium display a variety of proteins devoted to the efflux of bile salts or protons, to modify sugar metabolism or to prevent protein misfolding. In this manuscript, we review and discuss specific bile resistance mechanisms, as well as the processes responsible for the adaptation of bifidobacteria and lactobacilli to bile.
Coppin, Chris W; Jackson, Colin J; Sutherland, Tara; Hart, Peter J; Devonshire, Alan L; Russell, Robyn J; Oakeshott, John G
Esterases have been implicated in metabolic resistance to synthetic pyrethroids in several insect species but little is yet known of the molecular basis for these effects. In this work modern directed evolution technology was used to test to what extent it is possible to genetically enhance the pyrethroid hydrolytic activity of the E3 carboxylesterase from the blowfly Lucilia cuprina. High throughput screening of a random mutant library with individual stereoisomers of fluorogenic analogues of two type II pyrethroids identified 17 promising variants that were then also tested with the commercial pyrethroid deltamethrin. Between them, these variants displayed significantly improved activities for all the substrates tested. Amino acid substitutions at ten different residues were clearly implicated in the improvements, although most only enhanced activity for a subset of the stereoisomers. Several new combinations of the most promising amino acid substitutions were then made, and negative epistatic effects were found in most of the combinations, but significant improvements were also found in a minority of them. The best mutant recovered contained three amino acid changes and hydrolysed deltamethrin at more than 100 times the rate of wild-type E3. Structural analysis shows that nine of the ten mutated residues improving pyrethroid or analogue activities cluster in putative substrate binding pockets in the active site, with the three mutations of largest effect all increasing the volume of the acyl pocket.
Francisco P. Montanha
. Concerning the sublethal and lethal concentrations, Silver Catfish was sensitive to the tested concentrations of Cypermethrin, showing symptoms of poisoning, such as loss of balance, swimming alteration, dyspnea (they kept their mouths and opercula open, upright swimming and sudden spiral swimming movements. The intensity of such symptoms varied in proportion to the concentration used. The concentrations above 3.0mg/L were considered lethal to the species, since every animal exposed to concentrations between 3.0 and 20.0mg/L had died, while concentrations between 1.0 and 2.5mg/L were considered sublethal. Lethal concentration of Cypermethrin to Silver catfish, in 96 hours, was 1.71 milligram per liter of water. Concerning the sublethal concentration of Cypermethrin and Deltamethrin during the initial embryonic development, the results show that both pyrethroids had significantly decreased the analyzed parameters when comparing them with the control group. It was concluded that, even with the fish being more resistant to pyrethroids in comparison with other species, both the young animals and the ones in stage of embryonic development were susceptible to the effects of these pesticides.
The Ti fire found in high performance engines promotes the development of burn resistant Ti alloys. The burn resistant mechanism of Ti40 alloy is investigated. Ti40 alloy reveals good burn resistance. Its interfacial products between burning products and the matrix are tenacious,which retard the diffusion of oxygen into the matrix. Two burn resistant mechanisms, that is, fast scatter dispersion of heat and suppression of oxygen diffusion, are proposed.
Dang, Kai; Doggett, Stephen L; Veera Singham, G; Lee, Chow-Yang
The worldwide resurgence of bed bugs [both Cimex lectularius L. and Cimex hemipterus (F.)] over the past two decades is believed in large part to be due to the development of insecticide resistance. The transcriptomic and genomic studies since 2010, as well as morphological, biochemical and behavioral studies, have helped insecticide resistance research on bed bugs. Multiple resistance mechanisms, including penetration resistance through thickening or remodelling of the cuticle, metabolic resistance by increased activities of detoxification enzymes (e.g. cytochrome P450 monooxygenases and esterases), and knockdown resistance by kdr mutations, have been experimentally identified as conferring insecticide resistance in bed bugs. Other candidate resistance mechanisms, including behavioral resistance, some types of physiological resistance (e.g. increasing activities of esterases by point mutations, glutathione S-transferase, target site insensitivity including altered AChEs, GABA receptor insensitivity and altered nAChRs), symbiont-mediated resistance and other potential, yet undiscovered mechanisms may exist. This article reviews recent studies of resistance mechanisms and the genes governing insecticide resistance, potential candidate resistance mechanisms, and methods of monitoring insecticide resistance in bed bugs. This article provides an insight into the knowledge essential for the development of both insecticide resistance management (IRM) and integrated pest management (IPM) strategies for successful bed bug management.
Bell, J S; Adio, A O; Pitt, A; Hayman, L; Thorn, C E; Shore, A C; Whatmore, J L; Winlove, C P
Vascular diseases such as diabetes and hypertension cause changes to the vasculature that can lead to vessel stiffening and the loss of vasoactivity. The microstructural bases of these changes are not presently fully understood. We present a new methodology for stain-free visualization, at a microscopic scale, of the morphology of the main passive components of the walls of unfixed resistance arteries and their response to changes in transmural pressure. Human resistance arteries were dissected from subcutaneous fat biopsies, mounted on a perfusion myograph, and imaged at varying transmural pressures using a multimodal nonlinear microscope. High-resolution three-dimensional images of elastic fibers, collagen, and cell nuclei were constructed. The honeycomb structure of the elastic fibers comprising the internal elastic layer became visible at a transmural pressure of 30 mmHg. The adventitia, comprising wavy collagen fibers punctuated by straight elastic fibers, thinned under pressure as the collagen network straightened and pulled taut. Quantitative measurements of fiber orientation were made as a function of pressure. A multilayer analytical model was used to calculate the stiffness and stress in each layer. The adventitia was calculated to be up to 10 times as stiff as the media and experienced up to 8 times the stress, depending on lumen diameter. This work reveals that pressure-induced reorganization of fibrous proteins gives rise to very high local strain fields and highlights the unique mechanical roles of both fibrous networks. It thereby provides a basis for understanding the micromechanical significance of structural changes that occur with age and disease.
Full Text Available Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and “bypass” of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials.
Riveron, Jacob M; Chiumia, Martin; Menze, Benjamin D; Barnes, Kayla G; Irving, Helen; Ibrahim, Sulaiman S; Weedall, Gareth D; Mzilahowa, Themba; Wondji, Charles S
Deciphering the dynamics and evolution of insecticide resistance in malaria vectors is crucial for successful vector control. This study reports an increase of resistance intensity and a rise of multiple insecticide resistance in Anopheles funestus in Malawi leading to reduced bed net efficacy. Anopheles funestus group mosquitoes were collected in southern Malawi and the species composition, Plasmodium infection rate, susceptibility to insecticides and molecular bases of the resistance were analysed. Mosquito collection revealed a predominance of An. funestus group mosquitoes with a high hybrid rate (12.2 %) suggesting extensive species hybridization. An. funestus sensu stricto was the main Plasmodium vector (4.8 % infection). Consistently high levels of resistance to pyrethroid and carbamate insecticides were recorded and had increased between 2009 and 2014. Furthermore, the 2014 collection exhibited multiple insecticide resistance, notably to DDT, contrary to 2009. Increased pyrethroid resistance correlates with reduced efficacy of bed nets (change in resistance dynamics is mirrored by prevalent resistance mechanisms, firstly with increased over-expression of key pyrethroid resistance genes (CYP6Pa/b and CYP6M7) in 2014 and secondly, detection of the A296S-RDL dieldrin resistance mutation for the first time. However, the L119F-GSTe2 and kdr mutations were absent. Such increased resistance levels and rise of multiple resistance highlight the need to rapidly implement resistance management strategies to preserve the effectiveness of existing insecticide-based control interventions.
Full Text Available Abstract Background Pyrethroids and pyrethrins are widely used insecticides. Extensive applications not only result in pest resistance to these insecticides, but also may lead to environmental issues and human exposure. Numerous studies have shown that very high exposure to pyrethroids might cause potential problems to man and aquatic organisms. Therefore, it is important to develop a rapid and efficient disposal process to eliminate or minimize contamination of surface water, groundwater and agricultural products by pyrethroid insecticides. Bioremediation is considered to be a reliable and cost-effective technique for pesticides abatement and a major factor determining the fate of pyrethroid pesticides in the environment, and suitable esterase is expected to be useful for potential application for detoxification of pyrethroid residues. Soil is a complex environment considered as one of the main reservoirs of microbial diversity on the planet. However, most of the microorganisms in nature are inaccessible as they are uncultivable in the laboratory. Metagenomic approaches provide a powerful tool for accessing novel valuable genetic resources (novel enzymes and developing various biotechnological applications. Results The pyrethroid pesticides residues on foods and the environmental contamination are a public safety concern. Pretreatment with pyrethroid-hydrolyzing esterase has the potential to alleviate the conditions. To this end, a pyrethroid-hydrolyzing esterase gene was successfully cloned using metagenomic DNA combined with activity-based functional screening from soil, sequence analysis of the DNA responsible for the pye3 gene revealed an open reading frame of 819 bp encoding for a protein of 272 amino acid residues. Extensive multiple sequence alignments of the deduced amino acid of Pye3 with the most homologous carboxylesterases revealed moderate identity (45–49%. The recombinant Pye3 was heterologously expressed in E. coli BL21(DE3
Surendran Sinnathamby N
Full Text Available Abstract Background Anopheles subpictus s.l., an important malaria vector in Sri Lanka, is a complex of four morphologically identified sibling species A-D. Species A-D reportedly differ in bio-ecological traits that are important for vector control. We investigated possible variations that had not been reported previously, in the susceptibility to common insecticides and resistance mechanisms among the An. subpictus sibling species. Methods Adult An. subpictus were collected from localities in four administrative districts in the dry zone of Sri Lanka. Single female isoprogeny lines were established and sibling species status determined according to reported egg morphology. World Health Organization's standard protocols were used for insecticide bioassays and biochemical assays to determine insecticide susceptibility and resistance mechanisms. Susceptibility of mosquitoes was tested against DDT (5%, malathion (4%, deltamethrin (0.05% and λ-cyhalothrin (0.05%. Biochemical basis for resistance was determined through assaying for esterase, glutathione-S-transferase and monooxygenase activities and the insensitivity of acetycholinesterase (AChE to propoxur inhibition. Results All sibling species were highly resistant to DDT. However there were significant differences among the sibling species in their susceptibility to the other tested insecticides. Few species A could be collected for testing, and where testing was possible, species A tended to behave more similarly to species C and D than to B. Species B was more susceptible to all the tested insecticides than the other sibling species. This difference may be attributed to the predominance of species B in coastal areas where selection pressure due to indoor residual spraying of insecticides (IRS was lower. However there were significant differences between the more inland species C and D mainly towards pyrethroids. Higher GST activities in species C and D might have contributed to their greater
Full Text Available Abstract Background To manage the kdr pyrethroid-resistance in Anopheline malaria vectors, new compounds or new strategies are urgently needed. Recently, mixing repellents (DEET and a non-pyrethroid insecticide (propoxur was shown to be as effective as deltamethrin, a standard pyrethroid, under laboratory conditions, because of a strong synergy between the two compounds. In the present study, the interactions between two repellents (DEET and KBR 3023 and a non-pyrethroid insecticide (pyrimiphos methyl or PM on netting were investigated. The residual efficacy and the inhibition of blood feeding conferred by these mixtures were assessed against Anopheles gambiae mosquitoes. Methods DEET and KBR 3023 were mixed with pyrimiphos methyl (PM, a organophosphate (OP insecticide. The performance of mono- and bi-impregnated nets against adult mosquitoes was assessed using a miniaturized, experimental hut system (laboratory tunnel tests that allows expression of behavioural responses to insecticide, particularly the mortality and blood feeding effects. Results Both mixtures (PM+DEET and PM+KBR3023 induced 95% mortality for more than two months compared with less than one week for each compound used alone, then reflecting a strong synergy between the repellents and PM. A similar trend was observed with the blood feeding rates, which were significantly lower for the mixtures than for each component alone. Conclusion Synergistic interactions between organophosphates and repellents may be of great interest for vector control as they may contribute to increase the residual life of impregnated materials and improve the control of pyrethroid-resistance mosquitoes. These results prompt the need to evaluate the efficacy of repellent/non-pyrethroid insecticide mixtures against field populations of An. gambiae showing high level of resistance to Ops and pyrethroids.
Hase, S.; Pieterse, C.M.J.; Loon, L.C. van
Some of non-pathogenic rhizosphere bacteria reduce disease by activating a resistance mechanism in the plant called rhizobacteria-mediated induced systemic resistance (ISR). Rhizobacteria-mediated ISR resembles classic pathogen-induced systemic acquired resistance (SAR) in that both types of induced
Ochomo, Eric; Bayoh, Nabie M; Kamau, Luna; Atieli, Francis; Vulule, John; Ouma, Collins; Ombok, Maurice; Njagi, Kiambo; Soti, David; Mathenge, Evan; Muthami, Lawrence; Kinyari, Teresa; Subramaniam, Krishanthi; Kleinschmidt, Immo; Donnelly, Martin James; Mbogo, Charles
Increasing pyrethroid resistance in malaria vectors has been reported in western Kenya where long lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the mainstays of vector control. To ensure the sustainability of insecticide-based malaria vector control, monitoring programs need to be implemented. This study was designed to investigate the extent and distribution of pyrethroid resistance in 4 Districts of western Kenya (Nyando, Rachuonyo, Bondo and Teso). All four Districts have received LLINs while Nyando and Rachuonyo Districts have had IRS campaigns for 3-5 years using pyrethroids. This study is part of a programme aimed at determining the impact of insecticide resistance on malaria epidemiology. Three day old adult mosquitoes from larval samples collected in the field, were used for bioassays using the WHO tube bioassay, and mortality recorded 24 hours post exposure. Resistance level was assigned based on the 2013 WHO guidelines where populations with Kenya. This resistance does not seem to be associated with either species or location. Insecticide resistance can vary within small geographical areas and such heterogeneity may make it possible to evaluate the impact of resistance on malaria and mosquito parameters within similar eco-epidemiological zones.
Yao, Ke-Wen; Wang, Jie-Dong
As a new type of pesticides and because of their high performance and low toxicity, pyrethroid insecticides are widely used in place of organochlorine insecticides both in agriculture and in the home. In the recent years, more and more evidence indicates that pyrethroid insecticides can reduce sperm count and motility, cause deformity of the sperm head, increase the count of abnormal sperm, damage sperm DNA and induce its aneuploidy rate, as well as affect sex hormone levels and produce reproductive toxicity. The present article reviews the advances in the studies of male reproductive toxicity of pyrethroid pesticides by experiment in animals and human population, discusses the mechanism of male reproductive toxicity of pesticides and raises some problems concerning the evaluation of human reproductive hazards.
Victor I. Band
Full Text Available Cationic antimicrobial peptides (CAMPs are important innate immune defenses that inhibit colonization by pathogens and contribute to clearance of infections. Gram-negative bacterial pathogens are a major target, yet many of them have evolved mechanisms to resist these antimicrobials. These resistance mechanisms can be critical contributors to bacterial virulence and are often crucial for survival within the host. Here, we summarize methods used by Gram-negative bacteria to resist CAMPs. Understanding these mechanisms may lead to new therapeutic strategies against pathogens with extensive CAMP resistance.
Potential use of Piper nigrum ethanol extract against pyrethroid-resistant Aedes aegypti larvae Utilização em potencial do extrato alcoólico de Piper nigrum como larvicida em Aedes aegypti resistente a piretróides
Naomi Kato Simas
Full Text Available Fractionation of Piper nigrum ethanol extract, biomonitored by assays on pyrethroid-resistant Aedes aegypti larvae yielded isolation of the larvicidal amides piperolein-A and piperine. Comparing LC50 values, the ethanol extract (0. 98 ppm was the most toxic, followed by piperolein-A (1. 46ppm and piperine (1. 53ppm.O fracionamento do extrato etanólico de Piper nigrum biomonitorado por ensaios em larvas de Aedes aegypti resistentes a piretróides resultou no isolamento das amidas larvicidas piperoleína-A e piperina. Comparando-se os valores de CL50, o extrato etanólico (0. 98ppm foi o mais tóxico, seguido pela piperoleína-A (1. 46ppm e piperina (1. 53ppm.
Shaner, Dale L; Lindenmeyer, Richard Bradley; Ostlie, Michael H
The intensive use of glyphosate alone to manage weeds has selected populations that are glyphosate resistant. The three mechanisms of glyphosate resistance that have been elucidated are (1) target-site mutations, (2) gene amplification and (3) altered translocation due to sequestration. What have we learned from the selection of these mechanisms, and how can we apply those lessons to future herbicide-resistant crops and new mechanisms of action? First, the diversity of glyphosate resistance mechanisms has helped further our understanding of the mechanism of action of glyphosate and advanced our knowledge of plant physiology. Second, the relatively rapid evolution of glyphosate-resistant weed populations provides further evidence that no herbicide is invulnerable to resistance. Third, as new herbicide-resistant crops are developed and new mechanisms of action are discovered, the weed science community needs to ensure that we apply the lessons we have learned on resistance management from the experience with glyphosate. Every new weed management system must be evaluated during development for its potential to select for resistance, and stewardship programs should be in place when the new program is introduced.
Huang Da; Wu Jun-Jie; Tang Yu-Hua
With the progress of the semiconductor industry,the resistive random-access memory (RAM) has drawn increasing attention.The discovery of the memristor has brought much attention to this study.Research has focused on the resistive switching characteristics of different materials and the analysis of resistive switching mechanisms.We discuss the resistive switching mechanisms of different materials in this paper and analyze the differences of those mechanisms from the view point of circuitry to establish their respective circuit models.Finally,simulations are presented.We give the prospect of using different materials in resistive RAM on account of their resistive switching mechanisms,which are applied to explain their resistive switchings.
Full Text Available Bortezomib (Velcade™ is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM. Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ~30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response.
Clark, Stephen L; Ogle, R Scott; Gantner, Andrew; Hall, Lenwood W; Mitchell, Gary; Giddings, Jeffrey; McCoole, Matthew; Dobbs, Michael; Henry, Kevin; Valenti, Ted
Hyalella azteca are epibenthic invertebrates that are widely used for toxicity studies. They are reported to be more sensitive to pyrethroid insecticides than most other test species, which has prompted considerable use of this species in toxicity testing of ambient surface waters where the presence of pyrethroids is suspected. However, resident H. azteca have been found in some ambient water bodies reported to contain surface water and/or sediment pyrethroid concentrations that are toxic to laboratory reared H. azteca. This observation suggests differences in the sensitivities of laboratory reared and field populations of H. azteca to pyrethroids. The goal of the present study was to determine the sensitivities of laboratory reared and field populations of H. azteca to the pyrethroids bifenthrin and cypermethrin. Specimens of H. azteca were collected from resident populations at field sites that are subject to varied land-use activities as well as from laboratory populations. These organisms were exposed to bifenthrin- or cypermethrin-spiked water in 96-h water-only toxicity tests. The resulting data demonstrated that: 1) field-collected populations in urban and agricultural settings can be >2 orders of magnitude less sensitive to the pyrethroids than laboratory reared organisms; 2) field-collected organisms varied in their sensitivity (possibly based on land-use activities), with organisms collected from undeveloped sites exhibiting sensitivities similar to laboratory reared organisms; and 3) the sensitivity of field-collected "tolerant" organisms increased in subsequent generations reared under laboratory conditions. Potential mechanisms for these differences are discussed.
This paper reviews the current status of our understanding of resistance mechanisms of three major classes of antifungal drugs for systemic use, amphotericin B (AMPH), flucytosine (5-FC) and several azole antifungals, in particular fluconazole (FLCZ), at the molecular and cellular levels. Although the number of reports of AMPH- or 5-FC-resistant fungal species and strains is limited, several mechanisms of resistance have been described. AMPH-resistant Candida have a marked decrease in ergosterol content compared with AMPH-susceptible control isolates. A lesion in the UMP-pyrophosphorylase is the most frequent determinant of 5-FC resistance in C. albicans. Recently resistance of C. albicans to azoles has become an increasing problem. Extensive biochemical studies have highlighted a significant diversity in mechanisms conferring resistance to FLCZ and other azoles, which include alterations in sterol biosynthesis, target site, uptake and efflux. Among them, the most important mechanism clinically is reduced access of the drug to the intracellular P450 14 DM target, probably because of the action of a multidrug resistance efflux pump, and overproduction of that target. However, other possible resistance mechanisms for azoles remain to be identified.
Ujihara, Kazuya; Mori, Tatsuya; Matsuo, Noritada
Development of pyrethroids for household use and recent advances in the syntheses of (1R)-trans-chrysanthemic acid, the acid moiety of most of the household pyrethroids, are reviewed. As another important acid moiety, we discovered norchrysanthemic acid to have a significant vapor action at room temperature when esterified with fluorobenzyl alcohols. In particular, 2,3,5,6-tetrafluoro-4-methoxymethylbenzyl (1R)-trans-norchrysanthemate (metofluthrin) exhibits the highest potency in mosquito coil formulations as well as the vapor action at room temperature against various mosquitoes. Structure-activity relationships of norchrysanthemic acid esters and synthetic studies of norchrysanthemic acid are discussed.
Esterly, John S; Richardson, Chad L; Eltoukhy, Noha S; Qi, Chao; Scheetz, Marc H
To summarize published data identifying known genetic mechanisms of antibiotic resistance in Acinetobacter baumannii and the correlating phenotypic expression of antibiotic resistance. MEDLINE databases (1966-July 15, 2010) were searched to identify original reports of genetic mechanisms of antibiotic resistance in A. baumannii. Numerous genetic mechanisms of resistance to multiple classes of antibiotics are known to exist in A. baumannii, a gram-negative bacterium increasingly implicated in nosocomial infections. Mechanisms may be constitutive or acquired via plasmids, integrons, and transposons. Methods of resistance include enzymatic modification of antibiotic molecules, modification of antibiotic target sites, expression of efflux pumps, and downregulation of cell membrane porin channel expression. Resistance to β-lactams appears to be primarily caused by β-lactamase production, including extended spectrum β-lactamases (b/aTEM, blaSHV, b/aTX-M,b/aKPC), metallo-β-lactamases (blaMP, blaVIM, bla, SIM), and most commonly, oxacillinases (blaOXA). Antibiotic target site alterations confer resistance to fluoroquinolones (gyrA, parC) and aminoglycosides (arm, rmt), and to a much lesser extent, β-lactams. Efflux pumps (tet, ade, abe) contribute to resistance against β-lactams, tetracyclines, fluoroquinolones, and aminoglycosides. Finally, porin channel deletion (carO, oprD) appears to contribute to β-lactam resistance and may contribute to rarely seen polymyxin resistance. Of note, efflux pumps and porin deletions as solitary mechanisms may not render clinical resistance to A. baumannii. A. baumannii possesses copious genetic resistance mechanisms. Knowledge of local genotypes and expressed phenotypes for A. baumannii may aid clinicians more than phenotypic susceptibilities reported in large epidemiologic studies. © 2011 SAGE Publications.
Lo, Roger S; Shi, Hubing
(V600)BRAF mutation was identified as an ideal target for clinical therapy due to its indispensable roles in supporting melanoma initiation and progression. Despite the fact that BRAF inhibitors (BRAFi) can elicit anti-tumor responses in the majority of treated patients and confer overall survival benefits, acquired drug resistance is a formidable obstacle to long-term management of the disease. Several aberrant events including RTK upregulation, NRAS mutation, mutant BRAF amplification or alternative splicing, and MEK mutation have been reported as acquired BRAFi resistance mechanisms. Clinially, detection of these resistance mechanisms help understand drug response patterns and help guide combinatorial therapeutic strategies. Therefore, quick and accurate diagnosis of the resistant mechanisms in tumor biopsies has become an important starting point for personalized therapy. In this chapter, we review the major acquired BRAFi resistance mechanisms, highlight their therapeutic implications, and provide the diagnostic methods from clinical samples.
Full Text Available Obesity is now widespread around the world. Obesity-associated chronic low-grade inflammation is responsible for the decrease of insulin sensitivity, which makes obesity a major risk factor for insulin resistance and related diseases such as type 2 diabetes mellitus and metabolic syndromes. The state of low-grade inflammation is caused by overnutrition which leads to lipid accumulation in adipocytes. Obesity might increase the expression of some inflammatory cytokines and activate several signaling pathways, both of which are involved in the pathogenesis of insulin resistance by interfering with insulin signaling and action. It has been suggested that specific factors and signaling pathways are often correlated with each other; therefore, both of the fluctuation of cytokines and the status of relevant signaling pathways should be considered during studies analyzing inflammation-related insulin resistance. In this paper, we discuss how these factors and signaling pathways contribute to insulin resistance and the therapeutic promise targeting inflammation in insulin resistance based on the latest experimental studies.
张杰; 顾怡明; 俞云松; 周志慧; 杜小玲
@@The main drug-resistance mechanism of gram-negative bacteria is producing β-lactamases. Two kinds of enzymes cause drug resistance by hydrolyzing oxyimino-cephalosporins and aztreonam: one is chromosomally encoded AmpC β-lactamases, the other is plasmid-mediated extended-spectrum β-lactamases (ESBLs). Enterobacter cloacae can produce both of them, so that these strains are seriously resistance to many antibiotics. In order to study the main drug-resistant mechanism in Enterobacter cloacae, PCR and nucleotide sequencing were performed on 58 multidrug resistant strains.
Domínguez, M A; Liñares, J; Martín, R
Methicillin-resistant Staphylococcus aureus (MRSA) strains are among the most common nosocomial pathogens. The most significant mechanism of resistance to methicillin in this-species is the acquisition of a genetic determinant (mecA gene). However, resistance seems to have a more complex molecular basis, since additional chromosomal material is involved in such resistance. Besides, overproduction of penicillinase and/or alterations in the PBPs can contribute to the formation of resistance phenotypes. Genetic and environmental factors leading to MRSA are reviewed.
Zhang, Lan; Shi, Jing; Shi, Xueyan; Liang, Pei; Gao, Junping; Gao, Xiwu
Mechanisms of esterase-mediated pyrethroid resistance were analyzed based on our previous works in a strain of the housefly, Musca domestica. The carboxylesterase gene, MdalphaE7, was cloned and sequenced from susceptible (CSS) and resistant (CRR) strains, and a total of nine amino acid substitutions were found. The mutation, Trp(251)-Ser appeared to play a role in beta-cypermethrin resistance and cross-resistance between organophosphates (OPs) and pyrethroids in the CRR strain. Quantitative real-time PCR showed that MdalphaE7 was over-expressed in the CRR strain, the reciprocal cross progeny F(1) and back-cross progeny BC(2) compared with the CSS strain, respectively. Two alpha-cynaoester substrates as surrogates for beta-cypermethrin and deltamethrin, were synthesized to determine the pyrethroid hydrolase activity. Results showed that carboxylesterases from the CRR strain hydrolyzed cypermethrin/deltamethrin-like substrate 9.05- and 13.53-fold more efficiently than those from the CSS strain, respectively. Our studies suggested that quantitative and qualitative changes in the carboxylesterase might contribute together to pyrethroid resistance in the CRR strain.
Lohiya, Vipin; Aragon-Ching, Jeanny B.; Sonpavde, Guru
Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide. Here, we discuss the various mechanisms of resistance to chemotherapy in metastatic CRPC and the potential role of emerging regimens and agents in varying clinical phases of development.
Deng Shi-qiao; Ren Lu-quan; Liu Yan; Han Zhi-wu
The tangent resistance on the interface of the soil-moldboard is an important component of the resistance to moving soil . We developed simplified mechanical models to analyze this resistance. We found that it is composed of two components, the frictional and adhesive resistances. These two components originate from the soil pore, which induced a capillary suction effect, and the soil-moldboard contact area produced tangent adhesive resistance. These two components varied differently with soil moisture. Thus we predicted that resistance reduction against soil exerted on the non-smooth bionic moldboard is mainly due to the elimination of capillary suction and the reduction of physical-chemical adsorption of soil.
Islam, Md Mahmudul; Hameed, H M Adnan; Mugweru, Julius; Chhotaray, Chiranjibi; Wang, Changwei; Tan, Yaoju; Liu, Jianxiong; Li, Xinjie; Tan, Shouyong; Ojima, Iwao; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Zhang, Tianyu
Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance.
Edward K Thomsen
Full Text Available BACKGROUND: There has been rapid scale-up of malaria vector control in the last ten years. Both of the primary control strategies, long-lasting pyrethroid treated nets and indoor residual spraying, rely on the use of a limited number of insecticides. Insecticide resistance, as measured by bioassay, has rapidly increased in prevalence and has come to the forefront as an issue that needs to be addressed to maintain the sustainability of malaria control and the drive to elimination. Zambia's programme reported high levels of resistance to the insecticides it used in 2010, and, as a result, increased its investment in resistance monitoring to support informed resistance management decisions. METHODOLOGY/PRINCIPAL FINDINGS: A country-wide survey on insecticide resistance in Zambian malaria vectors was performed using WHO bioassays to detect resistant phenotypes. Molecular techniques were used to detect target-site mutations and microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was resistant to pyrethroids, DDT and carbamates, with potential organophosphate resistance in one population. The resistant phenotypes were conferred by both target-site and metabolic mechanisms. Anopheles funestus s.s. was largely resistant to pyrethroids and carbamates, with potential resistance to DDT in two locations. The resistant phenotypes were conferred by elevated levels of cytochrome p450s. CONCLUSIONS/SIGNIFICANCE: Currently, the Zambia National Malaria Control Centre is using these results to inform their vector control strategy. The methods employed here can serve as a template to all malaria-endemic countries striving to create a sustainable insecticide resistance management plan.
Chedik, Lisa; Bruyere, Arnaud; Le Vee, Marc; Stieger, Bruno; Denizot, Claire; Parmentier, Yannick; Potin, Sophie; Fardel, Olivier
Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulatory effects of these pesticides towards activities of main ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, using transporter-overexpressing cells. The pyrethroids allethrin and tetramethrin were found to inhibit various ABC and SLC drug transporters, including multidrug resistance-associated protein (MRP) 2, breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP) 1B1, organic anion transporter (OAT) 3, multidrug and toxin extrusion transporter (MATE) 1, organic cation transporter (OCT) 1 and OCT2, with IC50 values however ranging from 2.6 μM (OCT1 inhibition by allethrin) to 77.6 μM (OAT3 inhibition by tetramethrin) and thus much higher than pyrethroid concentrations (in the nM range) reached in environmentally pyrethroid-exposed humans. By contrast, allethrin and tetramethrin cis-stimulated OATP2B1 activity and failed to alter activities of OATP1B3, OAT1 and MATE2-K, whereas P-glycoprotein activity was additionally moderately inhibited. Twelve other pyrethoids used at 100 μM did not block activities of the various investigated transporters, or only moderately inhibited some of them (inhibition by less than 50%). In silico analysis of structure-activity relationships next revealed that molecular parameters, including molecular weight and lipophilicity, are associated with transporter inhibition by allethrin/tetramethrin and successfully predicted transporter inhibition by the pyrethroids imiprothrin and prallethrin. Taken together, these data fully demonstrated that two pyrethoids, i.e., allethrin and tetramethrin, can
Chedik, Lisa; Bruyere, Arnaud; Le Vee, Marc; Stieger, Bruno; Denizot, Claire; Parmentier, Yannick; Potin, Sophie; Fardel, Olivier
Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulatory effects of these pesticides towards activities of main ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, using transporter-overexpressing cells. The pyrethroids allethrin and tetramethrin were found to inhibit various ABC and SLC drug transporters, including multidrug resistance-associated protein (MRP) 2, breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP) 1B1, organic anion transporter (OAT) 3, multidrug and toxin extrusion transporter (MATE) 1, organic cation transporter (OCT) 1 and OCT2, with IC50 values however ranging from 2.6 μM (OCT1 inhibition by allethrin) to 77.6 μM (OAT3 inhibition by tetramethrin) and thus much higher than pyrethroid concentrations (in the nM range) reached in environmentally pyrethroid-exposed humans. By contrast, allethrin and tetramethrin cis-stimulated OATP2B1 activity and failed to alter activities of OATP1B3, OAT1 and MATE2-K, whereas P-glycoprotein activity was additionally moderately inhibited. Twelve other pyrethoids used at 100 μM did not block activities of the various investigated transporters, or only moderately inhibited some of them (inhibition by less than 50%). In silico analysis of structure-activity relationships next revealed that molecular parameters, including molecular weight and lipophilicity, are associated with transporter inhibition by allethrin/tetramethrin and successfully predicted transporter inhibition by the pyrethroids imiprothrin and prallethrin. Taken together, these data fully demonstrated that two pyrethoids, i.e., allethrin and tetramethrin, can
Mubarak Hossain, Muhammad; Suzuki, Tadahiko; Sato, Norio; Sato, Itaru; Takewaki, Tadashi; Suzuki, Koichi; Tachikawa, Eiichi; Kobayashi, Haruo
and the two type II pyrethroids indicating that dopaminergic circuitry, striatal DA in particular, may be a pyrethroid target and that pyrethroids may be acting on striatal DA by multiple mechanisms.
Full Text Available The dissemination of resistance among bacteria has been facilitated by the fact that resistance genes are usually located on a diverse and evolving set of transmissible plasmids. However, the mechanisms generating diversity and enabling adaptation within highly successful resistance plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we have performed a detailed analysis of the mobilome (the entire mobile genetic element content of a set of previously sequenced carbapenemase-producing Enterobacteriaceae (CPE from the National Institutes of Health Clinical Center. This analysis revealed that plasmid reorganizations occurring in the natural context of colonization of human hosts were overwhelmingly driven by genetic rearrangements carried out by replicative transposons working in concert with the process of homologous recombination. A more complete understanding of the molecular mechanisms and evolutionary forces driving rearrangements in resistance plasmids may lead to fundamentally new strategies to address the problem of antibiotic resistance.
Abstract: Chlamydia Trachomatis (C.T.) is one of the most common pathogens of human sexually transmitted diseases. Treatment of C.T. infection primarily depends on Tetracyclines, Macrolides and Quinolones, but with the wide use of antibiotics an increasing number of drug-resistant Chlamydia trachomatis cases have been reported. This review summarizes the resistant conditions and the possible resistance mechanisms of C.T..
Sakagami, Y; Yokoyama, H; Nishimura, H.; Ose, Y; Tashima, T.
The mechanisms of resistance of Pseudomonas aeruginosa to benzalkonium chloride (BC) were studied. The effluence of cell components was observed in susceptible P. aeruginosa by electron microscopy, but resistant P. aeruginosa seemed to be undamaged. No marked changes in cell surface potential between Escherichia coli NIHJC-2 and a spheroplast strain were found. The contents of phospholipids (PL) and fatty and neutral lipids (FNL) in the cell walls of resistant P. aeruginosa were higher than t...
Jagers op Akkerhuis, G.A.J.M.
The aim of this thesis was to obtain mechanistic information about how the toxicity of pesticides in the field is affected by physical factors, pesticide bioavailability and arthropod behaviour. The pyrethroid insecticide deltamethrin and linyphiid spiders were selected as pesticide-effect model. In
Hansen, Martin Rune; Jørs, Erik; Lander, Flemming;
, cumulative exposure) was assessed from questionnaire data. Participants were asked about symptoms of diabetes. Blood samples were analyzed for glycosylated hemoglobin (HbA1c), a measure of glucose regulation. No association was found between pyrethroid exposure and diabetes symptoms. The prevalence...
Full Text Available Arsenic is the most pervasive environmental substance and is classified by the International Agency for Research on Cancer as a Group 1 human carcinogen. Nearly every organism has resistance pathways for inorganic arsenic, and in bacteria, their genes are found in arsenic resistance (ars operons. Recently, a parallel pathway for organic arsenicals has been identified. The ars genes responsible for the organoarsenical detoxification includes arsM, which encodes an As(III S-adenosylmethionine methyltransferase, arsI, which encodes a C–As bond lyase, and arsH, which encodes a methylarsenite oxidase. The identification and properties of arsM, arsI and arsH are described in this review.
Matzrafi, Maor; Gadri, Yaron; Frenkel, Eyal; Rubin, Baruch; Peleg, Zvi
Herbicide resistant weeds are becoming increasingly common, threatening global food security. Here, we present BrIFAR: a new model system for the functional study of mechanisms of herbicide resistance in grass weeds. We have developed a large collection of Brachypodium accessions, the BrI collection, representing a wide range of habitats. Wide screening of the responses of the accessions to four major herbicide groups (PSII, ACCase, ALS/AHAS and EPSPS inhibitors) identified 28 herbicide-resistance candidate accessions. Target-site resistance to PSII inhibitors was found in accessions collected from habitats with a known history of herbicide applications. An amino acid substitution in the psbA gene (serine264 to glycine) conferred resistance and also significantly affected the flowering and shoot dry weight of the resistant accession, as compared to the sensitive accession. Non-target site resistance to ACCase inhibitors was found in accessions collected from habitats with a history of herbicide application and from a nature reserve. In-vitro enzyme activity tests and responses following pre-treatment with malathion (a cytochrome-P450 inhibitor) indicated sensitivity at the enzyme level, and give strong support to diclofop-methyl and pinoxaden enhanced detoxification as NTS resistance mechanism. BrIFAR can promote better understanding of the evolution of mechanisms of herbicide resistance and aid the implementation of integrative management approaches for sustainable agriculture. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Loganzo, Frank; Sung, Matthew; Gerber, Hans-Peter
Drug resistance limits the effectiveness of cancer therapies. Despite attempts to develop curative anticancer treatments, tumors evolve evasive mechanisms limiting durable responses. Hence, diverse therapies are used to attack cancer, including cytotoxic and targeted agents. Antibody-drug conjugates (ADC) are biotherapeutics designed to deliver potent cytotoxins to cancer cells via tumor-specific antigens. Little is known about the clinical manifestations of drug resistance to this class of therapy; however, recent preclinical studies reveal potential mechanisms of resistance. Because ADCs are a combination of antibody and small molecule cytotoxin, multifactorial modes of resistance are emerging that are inherent to the structure and function of the ADC. Decreased cell-surface antigen reduces antibody binding, whereas elevated drug transporters such as MDR1 and MRP1 reduce effectiveness of the payload. Inherent to the uniqueness of the ADC, other novel resistance mechanisms are emerging, including altered antibody trafficking, ADC processing, and intracellular drug release. Most importantly, the modular nature of the ADC allows components to be switched and replaced, enabling development of second-generation ADCs that overcome acquired resistance. This review is intended to highlight recent progress in our understanding of ADC resistance, including approaches to create preclinical ADC-refractory models and to characterize their emerging mechanisms of resistance. Mol Cancer Ther; 15(12); 2825-34. ©2016 AACR.
Altena, van S.E.C.
The aim of this thesis was to define and test biomarkers for disease resistance in dairy cows and to determine the underlying mechanism in natural disease resistance. The health status of the cows is an important issue in dairy farming. Due to the mandatory reduction in the use of antibiotics, alter
The goal of this paper is to present a systematic diagnostic approach towards the characterization of herbicide resistance in a given weed population with regards to profile (single, multiple, cross resistance), magnitude (fold level), mechanism, and related bio-physiological aspects. Diagnosing her...
Lindsey R. Boone
Full Text Available Background. Alterations in expression of hepatic genes that could contribute to resistance to dietary cholesterol were investigated in Sprague-Dawley rats, which are known to be resistant to the serum cholesterol raising action of dietary cholesterol. Methods. Microarray analysis was used to provide a comprehensive analysis of changes in hepatic gene expression in rats in response to dietary cholesterol. Changes were confirmed by RT-PCR analysis. Western blotting was employed to measure changes in hepatic cholesterol 7α hydroxylase protein. Results. Of the 28,000 genes examined using the Affymetrix rat microarray, relatively few were significantly altered. As expected, decreases were observed for several genes that encode enzymes of the cholesterol biosynthetic pathway. The largest decreases were seen for squalene epoxidase and lanosterol 14α demethylase (CYP 51A1. These changes were confirmed by quantitative RT-PCR. LDL receptor expression was not altered by dietary cholesterol. Critically, the expression of cholesterol 7α hydroxylase, which catalyzes the rate-limiting step in bile acid synthesis, was increased over 4-fold in livers of rats fed diets containing 1% cholesterol. In contrast, mice, which are not resistant to dietary cholesterol, exhibited lower hepatic cholesterol 7α hydroxylase (CYP7A1 protein levels, which were not increased in response to diets containing 2% cholesterol.
Bhuvanesh Sukhlal Kalal
Full Text Available Melanoma is a most dangerous and deadly type of skin cancer, and considered intrinsically resistant to both radiotherapy and chemotherapy. It has become a major public health concern as the incidence of melanoma has been rising steadily over recent decades with a 5-year survival remaining less than 5%. Detection of the disease in early stage may be curable, but late stage metastatic disease that has spread to other organs has an extremely poor prognosis with a median survival of less than 10 months. Since metastatic melanoma is unresponsive to therapy that is currently available, research is now focused on different treatment strategies such as combinations of surgery, chemotherapy and radiotherapy. The molecular basis of resistance to chemotherapy seen in melanoma is multifactorial; defective drug transport system, altered apoptotic pathway, deregulation of apoptosis and/or changes in enzymatic systems that mediate cellular metabolic machinery. Understanding of alterations in molecular processes involved in drug resistance may help in developing new therapeutic approaches to treatment of malignant melanoma.
Ee Wah Lim
Full Text Available Resistive switching effect in transition metal oxide (TMO based material is often associated with the valence change mechanism (VCM. Typical modeling of valence change resistive switching memory consists of three closely related phenomena, i.e., conductive filament (CF geometry evolution, conduction mechanism and temperature dynamic evolution. It is widely agreed that the electrochemical reduction-oxidation (redox process and oxygen vacancies migration plays an essential role in the CF forming and rupture process. However, the conduction mechanism of resistive switching memory varies considerably depending on the material used in the dielectric layer and selection of electrodes. Among the popular observations are the Poole-Frenkel emission, Schottky emission, space-charge-limited conduction (SCLC, trap-assisted tunneling (TAT and hopping conduction. In this article, we will conduct a survey on several published valence change resistive switching memories with a particular interest in the I-V characteristic and the corresponding conduction mechanism.
Full Text Available To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs of DNA gyrase (gyrA and gyrB and topoisomerase IV (parC and parE in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX, intermediate resistant to Levofloxacin (LVX and Sparfloxacin (SFX, and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.
Meng, Dong-Ya; Sun, Chang-Jian; Yu, Jing-Bo; Ma, Jun; Xue, Wen-Cheng
To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH) clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs) of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX), intermediate resistant to Levofloxacin (LVX) and Sparfloxacin (SFX), and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.
Maria Niures P.S. Matioli; Ricardo Nitrini
Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dy...
Zhang, Shuzhen; Zhang, Xiaolei; Shen, Jun; Li, Dongyang; Wan, Hu; You, Hong; Li, Jianhong
Indoxacarb belongs to a class of insecticides known as oxadiazines and is the first commercialized pyrazoline-type voltage-dependent sodium channel blocker. A moderate level of resistance to indoxacarb has evolved in field populations of Plutella xylostella from Central China. In the present study, cross-resistance, resistance stability and metabolic mechanisms of indoxacarb resistance were investigated in this moth species. A P. xylostella strain with a high level of resistance to indoxacarb was obtained through continuous selection in the laboratory. The strain showed cross-resistance to metaflumizone, beta-cypermethrin and chlorfenapyr, but no resistance to cyantraniliprole, chlorantraniliprole, abamectin, chlorfluazuron, spinosad and diafenthiuron compared with the susceptible strain. Synergism tests revealed that piperonyl butoxide (PBO) (synergistic ratio, SR=7.8) and diethyl maleate (DEF) (SR=3.5) had considerable synergistic effects on indoxacarb toxicity in the resistant strain (F58). Enzyme activity data showed there was an approximate 5.8-fold different in glutathione S-transferase (GST) and a 6.8-fold different in cytochrome P450 monooxygenase between the resistant strain (F58) and susceptible strain, suggesting that the increased activity of these two enzymes is likely the main detoxification mechanism responsible for the species' resistance to indoxacarb. These results will be helpful for insecticide resistance management strategies to delay the development of indoxacarb resistance in fields. Copyright © 2017. Published by Elsevier Inc.
Kaiser, Caroline; Kristensen, Michael; Jensen, Karl-Martin Vagn
The pollen beetle (Meligethes aeneus F.) is a serious pest in the northern countries in oilseed rape. To determine the present level of pyrethroid and neonicotinoid susceptibility of Danish pollen beetle populations, standardized methods recommended by IRAC (Insecticide Resistance Action Committee......) were used. Pollen beetle populations were collected from 47 locations of Denmark with the help of the consultants and the farmers of the various regions in 2014. Further six populations were tested from Sweden and one from Germany. In the following year 2015, the monitoring continued to find out......, if the resistance level which was determined in 2014 was stable in selected regions. Therefore pollen beetle populations from 14 locations in Denmark and five locations in Germany have been tested. For all tests the standardised methods for pyrethroids, the Adult-vial-test No. 11 and the Adult-vials-test No. 21...
Baron, Sophie; Hadjadj, Linda; Rolain, Jean-Marc; Olaitan, Abiola Olumuyiwa
Colistin, also referred to as polymyxin E, is an effective antibiotic against most multidrug-resistant Gram-negative bacteria and is currently used as a last-line drug for treating severe bacterial infections. Colistin resistance has increased gradually for the last few years, and knowledge of its multifaceted mechanisms is expanding. This includes the newly discovered plasmid-mediated colistin resistance gene mcr-1, which has been detected in over 20 countries within 3 months of its first report. We previously reported all of the known mechanisms of polymyxin resistance in our first review in 2014, but an update seems necessary in 2016, considering the significant recent discoveries that have been made in this domain. This review provides an update about what is already known, what is new, and some unresolved questions with respect to colistin resistance.
Full Text Available Abstract Background Pyrethroid pesticides are broad-spectrum pest control agents in agricultural production. Both agricultural and residential usage is continuing to grow, leading to the development of insecticide resistance in the pest and toxic effects on a number of nontarget organisms. Thus, it is necessary to hunt suitable enzymes including hydrolases for degrading pesticide residues, which is an efficient "green" solution to biodegrade polluting chemicals. Although many pyrethroid esterases have consistently been purified and characterized from various resources including metagenomes and organisms, the thermostable pyrethroid esterases have not been reported up to the present. Results In this study, we identified a novel pyrethroid-hydrolyzing enzyme Sys410 belonging to familyV esterases/lipases with activity-based functional screening from Turban Basin metagenomic library. Sys410 contained 280 amino acids with a predicted molecular mass (Mr of 30.8 kDa and was overexpressed in Escherichia coli BL21 (DE3 in soluble form. The optimum pH and temperature of the recombinant Sys410 were 6.5 and 55°C, respectively. The enzyme was stable in the pH range of 4.5-8.5 and at temperatures below 50°C. The activity of Sys410 decreased a little when stored at 4°C for 10 weeks, and the residual activity reached 94.1%. Even after incubation at 25°C for 10 weeks, it kept 68.3% of its activity. The recombinant Sys410 could hydrolyze a wide range of ρ-nitrophenyl esters, but its best substrate is ρ-nitrophenyl acetate with the highest activity (772.9 U/mg. The enzyme efficiently degraded cyhalothrin, cypermethrin, sumicidin, and deltamethrin under assay conditions of 37°C for 15 min, with exceeding 95% hydrolysis rate. Conclusion This is the first report to construct metagenomic libraries from Turban Basin to obtain the thermostable pyrethroid-hydrolyzing enzyme. The recombinant Sys410 with broad substrate specificities and high activity was the most
Antwi, Frank B; Reddy, Gadi V P
The toxicological effects of pyrethroids on non-target aquatic insects are mediated by several modes of entry of pyrethroids into aquatic ecosystems, as well as the toxicological characteristics of particular pyrethroids under field conditions. Toxicokinetics, movement across the integument of aquatic insects, and the toxicodynamics of pyrethroids are discussed, and their physiological, symptomatic and ecological effects evaluated. The relationship between pyrethroid toxicity and insecticide uptake is not fully defined. Based on laboratory and field data, it is likely that the susceptibility of aquatic insects (vector and non-vector) is related to biochemical and physiological constraints associated with life in aquatic ecosystems. Understanding factors that influence aquatic insects susceptibility to pyrethroids is critical for the effective and safe use of these compounds in areas adjacent to aquatic environments.
Maggy T Sikulu
Full Text Available We report on the accuracy of using near-infrared spectroscopy (NIRS to predict the age of Anopheles mosquitoes reared from wild larvae and a mixed age-wild adult population collected from pit traps after exposure to pyrethroids. The mosquitoes reared from wild larvae were estimated as <7 or ≥7 d old with an overall accuracy of 79%. The age categories of Anopheles mosquitoes that were not exposed to the insecticide papers were predicted with 78% accuracy whereas the age categories of resistant, susceptible and mosquitoes exposed to control papers were predicted with 82%, 78% and 79% accuracy, respectively. The ages of 85% of the wild-collected mixed-age Anopheles were predicted by NIRS as ≤8 d for both susceptible and resistant groups. The age structure of wild-collected mosquitoes was not significantly different for the pyrethroid-susceptible and pyrethroid-resistant mosquitoes (P = 0.210. Based on these findings, NIRS chronological age estimation technique for Anopheles mosquitoes may be independent of insecticide exposure and the environmental conditions to which the mosquitoes are exposed.
Ngufor, Corine; Fagbohoun, Josias; Critchley, Jessica; N'Guessan, Raphael; Todjinou, Damien; Malone, David; Akogbeto, Martin; Rowland, Mark
Malaria control today is threatened by widespread insecticide resistance in vector populations. The World Health Organization (WHO) recommends the use of a mixture of unrelated insecticides for indoor residual spraying (IRS) and long-lasting insecticidal nets (LNs) or as a combination of interventions for improved vector control and insecticide resistance management. Studies investigating the efficacy of these different strategies are necessary. The efficacy of Interceptor(®) G2 LN, a newly developed LN treated with a mixture of chlorfenapyr (a pyrrole) and alpha-cypermethrin (a pyrethroid), was compared to a combined chlorfenapyr IRS and Interceptor(®) LN (a standard alpha-cypermethrin LN) intervention in experimental huts in Cove Southern Benin, against wild, free-flying, pyrethroid-resistant Anopheles gambiae s.l. A direct comparison was also made with a pyrethroid-only net (Interceptor(®) LN) alone and chorfenapyr IRS alone. WHO resistance bioassays performed during the trial demonstrated a pyrethroid resistance frequency of >90% in the wild An. gambiae s.l. from the Cove hut site. Mortality in the control (untreated net) hut was 5%. Mortality with Interceptor(®) LN (24%) was lower than with chlorfenapyr IRS alone (59%, P chlorfenapyr IRS intervention and the mixture net (Interceptor(®) G2 LN) provided significantly higher mortality rates (73 and 76%, respectively) and these did not differ significantly between both treatments (P = 0.15). Interceptor LN induced 46% blood-feeding inhibition compared to the control untreated net, while chlorfenapyr IRS alone provided none. Both mixture/combination strategies also induced substantial levels of blood-feeding inhibition (38% with combined interventions and 30% with Interceptor(®) G2 LN). A similar trend of improved mortality of pyrethroid-resistant An. gambiae s.l. from Cove was observed with Interceptor(®) G2 LN (79%) compared to Interceptor LN (42%, P chlorfenapyr and alpha-cypermethrin together as a
Wilson, Daniel N
The ribosome is one of the main antibiotic targets in the bacterial cell. Crystal structures of naturally produced antibiotics and their semi-synthetic derivatives bound to ribosomal particles have provided unparalleled insight into their mechanisms of action, and they are also facilitating the design of more effective antibiotics for targeting multidrug-resistant bacteria. In this Review, I discuss the recent structural insights into the mechanism of action of ribosome-targeting antibiotics and the molecular mechanisms of bacterial resistance, in addition to the approaches that are being pursued for the production of improved drugs that inhibit bacterial protein synthesis.
Full Text Available Background: Anopheles stephensi is a sub-tropical species and has been considered as one of the most important vector of human malaria throughout the Middle East and South Asian region including the malarious areas of southern Iran. Current reports confirmed An. stephensi resistance to temephos in Oman and India. However, there is no comprehensive research on mechanisms of temephos resistance in An. stephensi in the literature. This study was designed in order to clarify the enzymatic and molecular mechanisms of temephos resistance in this species.Methods: Profile activities of α- and ß-esterases, mixed function oxidase (MFO, glutathione-S-transferase (GST, insensitive acetylcholinesterase, and para-nitrophenyl acetate (PNPA-esterase enzymes were tested for An. stephensi strain with resistance ratio of 15.82 to temephos in comparison with susceptible strain.Results: Results showed that the mean activity of α-EST, GST and AChE enzymes were classified as altered indicating metabolic mechanisms have considerable role in resistance of An. stephensi to temephos. Molecular study using PCR-RFLP method to trace the G119S mutation in ACE-1 gene showed lack of the mutation responsible for organophosphate insecticide resistance in the temephos-selected strain of An. stephensi.Conclusion: This study showed that the altered enzymes but not targets site insensitivity of ACE-1 are responsible for temephos resistance in An. stephensi in south of Iran.
El Zowalaty, Mohamed E; Al Thani, Asmaa A; Webster, Thomas J; El Zowalaty, Ahmed E; Schweizer, Herbert P; Nasrallah, Gheyath K; Marei, Hany E; Ashour, Hossam M
Antimicrobial resistance is one of the most serious public health issues facing humans since the discovery of antimicrobial agents. The frequent, prolonged, and uncontrolled use of antimicrobial agents are major factors in the emergence of antimicrobial-resistant bacterial strains, including multidrug-resistant variants. Pseudomonas aeruginosa is a leading cause of nosocomial infections. The abundant data on the increased resistance to antipseudomonal agents support the need for global action. There is a paucity of new classes of antibiotics active against P. aeruginosa. Here, we discuss recent antibacterial resistance profiles and mechanisms of resistance by P. aeruginosa. We also review future potential methods for controlling antibiotic-resistant bacteria, such as phage therapy, nanotechnology and antipseudomonal vaccines.
Nadai, Chiara; Treu, Laura; Campanaro, Stefano; Giacomini, Alessio; Corich, Viviana
From a technological point of view, yeast resistance to sulfite is of great interest and represents an important technological character for winemaking. Several mechanisms are involved, and strain-dependent strategies to obtain SO2 resistance can deeply influence wine quality, although this choice is less relevant in determining the technological performance of the strain during fermentation. In this study, to better understand the strain-specific mechanisms of resistance, 11 Saccharomyces cerevisiae strains, whose genomes have been previously sequenced, were selected. Their attitude towards sulfites, in terms of resistance and production, was evaluated, and RNA-sequencing of four selected strains was performed during fermentation process in synthetic grape must in the presence of SO2. Results demonstrated that at molecular level, the physical effect of SO2 triggered multiple stress responses in the cell and high tolerance to general enological stressing condition increased SO2 resistance. Adaptation mechanism due to high basal gene expression level rather than specific gene induction in the presence of sulfite seemed to be responsible in modulating strain resistance. This mechanism involved higher basal gene expression level of specific cell wall proteins, enzymes for lipid biosynthesis, and enzymes directly involved in SO2 assimilation pathway and efflux.
Sarret, C.; Manceau, A.; Eybert-Berard, L. [Univ. of Grenoble and CNRS (France). Environmental Geochemistry Group; Cuny, D.; Haluwyn, C. van [Lab. de Botanique et de Cryptogamie, Lille (France); Deruelle, S. [Institut d`Ecologie, Paris (France); Hazemann, J.L.; Menthonnex, J.J. [Univ. of Grenoble and CNRS (France). Environmental Geochemistry Group]|[CNRS, Grenoble (France). Lab. de Cristallographie; Soldo, Y. [CNRS, Grenoble (France). Lab. de Cristallographie
Some lichens have a unique ability to grow in heavily contaminated areas due to the development of adaptative mechanisms allowing a high tolerance to metals. Here the authors report on the chemical forms of Pb and Zn in the metal hyperaccumulator Diploschistes muscorum and of Pb in the metal tolerant lichen Xanthoria parietina. The speciation of Zn and Pb has been investigated by powder X-ray diffraction (XRD) and extended X-ray absorption fine structure (EXAFS) spectroscopy using the advanced third-generation synchrotron radiation source of the European synchrotron radiation facility (ESRF in Grenoble). This study reveals that in both lichens cells are protected from toxicity by complexation of heavy metals, but the strategies differ: in D. muscorum, Pb and Zn are accumulated through an enhanced synthesis of oxalate, which precipitates toxic elements as insoluble salts, whereas in X. parietina, Pb is complexed to carboxylic groups of the fungal cell walls. The authors conclude that hyperaccumulation of metals results from a reactive mechanism of organic acid production, whereas metallo-tolerance is achieved by a passive complexation to existing functional groups.
Arendrup, Maiken Cavling; Patterson, Thomas F
Invasive Candida infections remain an important cause of morbidity and mortality, especially in hospitalized and immunocompromised or critically ill patients. A limited number of antifungal agents from only a few drug classes are available to treat patients with these serious infections. Resistance can be either intrinsic or acquired. Resistance mechanisms are not exchanged between Candida; thus, acquired resistance either emerges in response to an antifungal selection pressure in the individual patient or, more rarely, occur due to horizontal transmission of resistant strains between patients. Although multidrug resistance is uncommon, increasing reports of multidrug resistance to the azoles, echinocandins, and polyenes have occurred in several Candida species, most notably Candida glabrata and more recently Candida auris. Drivers are overall antifungal use, subtherapeutic drug levels at sites of infection/colonization, drug sequestration in the biofilm matrix, and, in the setting of outbreaks, suboptimal infection control. Moreover, recent research suggests that DNA mismatch repair gene mutations may facilitate acquisition of resistance mutations in C. glabrata specifically. Diagnosis of antifungal-resistant Candida infections is critical to the successful management of patients with these infections. Reduction of unnecessary use of antifungals via antifungal stewardship is critical to limit multidrug resistance emergence. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: email@example.com.
Full Text Available The article is aimed at studying the effect of temperature on structure of intermetallic phases of the protective zinc layer. The main objective of the article is a description of the structure and the changes that can occur during the heating process. The first part of the article deals with the description of the structure and mechanical properties of the interfacial phases and their arrangement. The main part of the article is aimed at study of brittle intermetallic phases, which arise due to increased temperature. For this reason, a set of samples of steel CSN 11 321 (DC01 was prepared. These samples were subjected to thermal heating in the tempering furnace. Subsequently metallographic cross sections were prepared, observed and assessed using SEM microscopy and EDS analysis. Also accelerated corrosion tests and pull off bend tests were performed. Conclusion of the article is trying to explain the influence of intermetallic phases on degradation of the protective layer.
Tian, Xiangrui; Sun, Xingxing; Su, Jianya
The metaflumizone, which belongs to the class of voltage-dependent sodium channel blockers, was registered to control Spodoptera exigua on vegetables in China in 2009. The present study revealed S. exigua has developed high resistance to this novel chemistry insecticide shortly after 2-3 years application in Guangdong Province of China. The metabolic mechanisms for metaflumizone resistance in this insect were analysed. The inhibitor of esterases greatly potentiates the toxicity of this chemical against the field resistant populations. The synergism ratio is 5.7 and 3.4-fold for S. exigua collected from Huizhou, Guangdong Province in 2011 and 2012, respectively. The activity of esterases in field populations (HZ12) is also significantly greater than that in the susceptible strain, and further significantly increased by challenge with metaflumizone for 3 generations. However, the inhibitor of P450s or GSTs only has slight synergism on metaflumizone toxicity against resistant populations, and there are no obvious differences in activities of P450s or GSTs between resistant populations and the susceptible strain. These results suggest that esterases might take pivotal role in conferring metabolic resistance to metaflumizone in the field populations of S. exigua, and P450s or GSTs are not involved in this resistance. Moreover, flavin-dependent monooxygenases (FMOs) are discovered to involve in metaflumizone resistance in the field populations of S. exigua. The FMO inhibitor, methimazole, potentiates metaflumizone toxicity in resistant larva of this species substantially. The synergism ratios for methimazole in resistant populations HZ11 and HZ12 were 3.1 and 1.9, respectively. Enzymatic assays also revealed higher FMO activities in resistant populations than in the susceptible strain, and successive selection with metaflumizone further increased the FMO activity in the field resistant population, but not significantly. The higher FMO activities in the older larval
K. R. Kotsyuba
Full Text Available The paper deals with the basic medical scheme of antibiotics use for treatment of lesions caused by enterobacteria and mechanisms of resistance of Enterobacteriaceae to different classes of antibiotics. It is known that the main mechanisms of resistance to antibiotics are enzymatic inactivation, modification of the target, efflux, violation of conduct through the membrane and formation of metabolic shunt. The most common cases of resistance to beta-lactams among Enterobacteriaceae relate to production of plasmid and chromosomal beta-lactamases, violation of the permeability of the outer membrane, and modification of target penicillin binding proteins. Active release of antibiotics from the cell, or efflux, in Enterobacteriaceae is used for maintaining resistance to tetracyclines, macrolides, carbapenems. Genes of efflux system are localized on plasmids and contribute to rapid spreading among Enterobacteriaceae. Mutations are the basis of resistance to novobiocinum and rifampicinum. Enzymatic inactivation by modifying is typical for resistance to aminoglycosides. Three groups of enzymes are engaged in the process, by adding the molecule of acetic acid, phosphate or adenine. Joining of these groups is irreversible and leads to complete loss of biological activity of the antibiotic. Resistance to aminoglycosides appears also due to inhibition of drug penetration, that is associated with genetically determined mechanisms of electron transport through the membrane. Resistance to quinolones and fluoroquinolones is associated with the modification of topoisomerase II and IV which are targets of these groups of antibiotics. Resistance is possible as a result of changes in the structure of the target, breaching of penetration into the cell, and active release from the cell. The highest level of resistance is develope in the case of two- or three-stage mutations in one or the other, or both, subunits in different genes. At the same time, for breaching of
Full Text Available This is a case of a 22-year-old Hispanic male with a history of bipolar disorder and methamphetamine dependence who was admitted after presenting with suicidal ideations by slashing his throat with a machete. The patient had been smoking and inhaling “processed” pyrethroid for about eight weeks as an inexpensive methamphetamine substitute. He reported experiencing a “rush” similar to methamphetamine after using pyrethroid from liquid insecticide that had been heated (electrocuted or sprayed on hot metal sheets until it crystallized. The patient presented with no significant physical markings or findings but claimed to have his suicidal ideations precipitated by concerns of ill effects of pyrethroid on his health. He also had positive urine drug screen for methamphetamine, which he admitted to using on the day of admission. We conclude that it is important for physicians to maintain a high level of suspicion for alternate and uncommon substances of abuse as well as risks for suicidal tendencies in these patients.
Kjos, Morten; Nes, Ingolf F; Diep, Dzung B
The membrane proteins IIC and IID of the mannose phosphotransferase system (Man-PTS) together form a membrane-located complex that serves as a receptor for several different bacteriocins, including the pediocin-like class IIa bacteriocins and the class IIc bacteriocin lactococcin A. Bacterial strains sensitive to class IIa bacteriocins readily give rise to resistant mutants upon bacteriocin exposure. In the present study, we have therefore investigated lactococcin A-resistant mutants of Lactococcus lactis as well as natural food isolates of Listeria monocytogenes with different susceptibilities to class IIa bacteriocins. We found two major mechanisms of resistance. The first involves downregulation of Man-PTS gene expression, which takes place both in spontaneous resistant mutants and in natural resistant isolates. The second involves normal expression of the Man-PTS system, but the underlying mechanism of resistance for these cells is unknown. In some cases, the resistant phenotype was linked to a shift in the metabolism; i.e., reduced growth on glucose due to reduction in Man-PTS expression was accompanied by enhanced growth on another sugar, such as galactose. The implications of these findings in terms of metabolic heterogeneity are discussed.
Zavascki, Alexandre P; Carvalhaes, Cecília G; Picão, Renata C; Gales, Ana C
Pseudomonas aeruginosa and Acinetobacter baumannii are major nosocomial pathogens worldwide. Both are intrinsically resistant to many drugs and are able to become resistant to virtually any antimicrobial agent. An increasing prevalence of infections caused by multidrug-resistant (MDR) isolates has been reported in many countries. The resistance mechanisms of P. aeruginosa and A. baumannii include the production of beta-lactamases, efflux pumps, and target-site or outer membrane modifications. Resistance to multiple drugs is usually the result of the combination of different mechanisms in a single isolate or the action of a single potent resistance mechanism. There are many challenges in the treatment of MDR P. aeruginosa and A. baumannii, especially considering the absence of new antimicrobials in the drug-development pipeline. In this review, we present the major resistance mechanisms of P. aeruginosa and A. baumannii, and discuss how they can affect antimicrobial therapy, considering recent clinical, microbiological, pharmacokinetic and pharmacodynamic findings of the main drugs used to treat MDR isolates.
Naik, Milind Mohan; Dubey, Santosh Kumar
Lead (Pb) is non-bioessential, persistent and hazardous heavy metal pollutant of environmental concern. Bioremediation has become a potential alternative to the existing technologies for the removal and/or recovery of toxic lead from waste waters before releasing it into natural water bodies for environmental safety. To our best knowledge, this is a first review presenting different mechanisms employed by lead resistant bacteria to resist high levels of lead and their applications in cost effective and eco-friendly ways of lead bioremediation and biomonitoring. Various lead resistant mechanisms employed by lead resistant bacteria includes efflux mechanism, extracellular sequestration, biosorption, precipitation, alteration in cell morphology, enhanced siderophore production and intracellular lead bioaccumulation.
Wu, Pei; Zhang, Wenqi; Bay, Niels;
The dynamic mechanical response of resistance welding machine is very important to the weld quality in resistance welding especially in projection welding when collapse or deformation of work piece occurs. It is mainly governed by the mechanical parameters of machine. In this paper, a mathematical...... for both upper and lower electrode systems. This has laid a foundation for modeling the welding process and selecting the welding parameters considering the machine factors. The method is straightforward and easy to be applied in industry since the whole procedure is based on tests with no requirements...
Gomes, Cláudia; Martínez-Puchol, Sandra; Palma, Noemí; Horna, Gertrudis; Ruiz-Roldán, Lidia; Pons, Maria J; Ruiz, Joaquim
From its introduction in 1952 onwards, the clinical use of macrolides has been steadily increasing, both in human and veterinary medicine. Although initially designed to the treatment of Gram-positive microorganisms, this antimicrobial family has also been used to treat specific Gram-negative bacteria. Some of them, as azithromycin, are considered in the armamentarium against Enterobacteriaceae infections. However, the facility that this bacterial genus has to gain or develop mechanisms of antibiotic resistance may compromise the future usefulness of these antibiotics to fight against Enterobacteriaceae infections. The present review is focused on the mechanisms of macrolide resistance, currently described in Enterobacteriaceae.
Alphonsine A Koffi
Full Text Available Insecticide resistance constitutes a major threat that may undermine current gain in malaria control in most endemic countries. National Malaria Control Programmes (NMCPs need as much information as possible on the resistance status of malaria vectors and underlying mechanisms in order to implement the most relevant and efficient control strategy. Bioassays, biochemical and molecular analysis were performed on An. gambiae collected in six sentinel sites in Côte d'Ivoire. The sites were selected on the basis of their bioclimatic status and agricultural practices. An. gambiae populations across sites showed high levels of resistance to organochloride, pyrethroid and carbamate insecticides. The kdr and ace-1(R mutations were detected in almost all sentinel sites with mosquitoes on the coastal and cotton growing areas mostly affected by these mutations. At almost all sites, the levels of detoxifying enzymes (mixed-function oxidases (MFOs, non-specific esterases (NSE and glutathione-S-transferases (GSTs in An. gambiae populations were significantly higher than the levels found in the susceptible strain Kisumu. Pre-exposure of mosquitoes to PBO, an inhibitor of MFOs and NSEs, significantly increased mortality rates to pyrethroids and carbamates in mosquitoes but resistance in most cases was not fully synergised by PBO, inferring a residual role of additional mechanisms, including kdr and ace-1 site insensitivity. The large distribution of resistance in Côte d'Ivoire raises an important question of whether to continue to deploy pyrethroid-based long-lasting insecticidal nets (LLINs and insecticide residual spraying (IRS towards which resistance continues to rise with no guarantee that the level of resistance would not compromise their efficacy. Innovative strategies that combine insecticide and synergists in LLINs or spatially LLIN and an effective non-pyrethroid insecticide for IRS could be in the short term the best practice for the NMCP to manage
Juntarajumnong, Waraporn; Pimnon, Sunthorn; Bangs, Michael J; Thanispong, Kanutcharee; Chareonviriyaphap, Theeraphap
Establishing baseline insecticide discriminating doses is crucial in accurately determining susceptibility status and changing temporal patterns of physiological response in mosquito populations. Pyrethroids are the predominant chemicals used for controlling adult Aedes aegypti and Ae. albopictus, both vectors of dengue viruses, in Thailand. Presently, only 2 pyrethroids, permethrin and lambda-cyhalothrin, have published diagnostic dose rates for monitoring Ae. aegypti. This study established the diagnostic lethal concentrations for 6 different pyrethroids available in Thailand for dengue vector control. United States Department of Agriculture insecticide-susceptible strain of Ae. aegypti was used to establish the baseline concentrations for subsequent susceptibility testing of field populations. Our findings showed lower discriminating concentrations for lambda-cyhalothrin and permethrin than those recommended by the World Health Organization (WHO), at 2.5- and 1.7-fold lower dosing, respectively. The susceptibility status of 3 different geographical populations of field-collected Ae. aegypti were tested using the standard WHO procedures. All 3 field strains demonstrated varying levels of physiological resistance to each compound. We conclude that establishing the baseline diagnostic concentration of an insecticide is of paramount importance in accurately determining the susceptibility status in field-collected mosquitoes. If possible, discriminating doses should be established for all insecticides and test assays run concurrently with a known susceptible strain for more accurate monitoring of resistance in mosquito populations in Thailand.
Goindin, Daniella; Delannay, Christelle; Gelasse, Andric; Ramdini, Cédric; Gaude, Thierry; Faucon, Frédéric; David, Jean-Philippe; Gustave, Joël; Vega-Rua, Anubis; Fouque, Florence
In the Guadeloupe and Saint Martin islands, Aedes aegypti mosquitoes are the only recognized vectors of dengue, chikungunya, and Zika viruses. For around 40 years, malathion was used as a mosquito adulticide and temephos as a larvicide. Since the European Union banned the use of these two insecticide molecules in the first decade of the 21st century, deltamethrin and Bacillus thuringiensis var. israelensis are the remaining adulticide and larvicide, respectively, used in Guadeloupe. In order to improve the management of vector control activities in Guadeloupe and Saint Martin, we investigated Ae. aegypti resistance to and mechanisms associated with deltamethrin, malathion, and temephos. Ae. aegypti mosquitoes were collected from six different localities of Guadeloupe and Saint Martin. Larvae were used for malathion and temephos bioassays, and adult mosquitoes for deltamethrin bioassays, following World Health Organization recommendations. Knockdown resistance (Kdr) genotyping for V1016I and F1534C mutations, and expression levels of eight enzymes involved in detoxification mechanisms were examined in comparison with the susceptible reference Bora Bora strain. Resistance ratios (RR50) calculated for Ae. aegypti larvae showed high resistance levels to temephos (from 8.9 to 33.1-fold) and low resistance levels to malathion (from 1.7 to 4.4-fold). Adult females displayed moderate resistance levels to deltamethrin regarding the time necessary to affect 50% of individuals, varying from 8.0 to 28.1-fold. Molecular investigations on adult mosquitoes showed high resistant allele frequencies for V1016I and F1534C (from 85 to 96% and from 90 to 98%, respectively), as well as an overexpression of the glutathione S-transferase gene, GSTe2, the carboxylesterase CCEae3a, and the cytochrome genes 014614, CYP6BB2, CYP6M11, and CYP9J23. Ae. aegypti populations from Guadeloupe and Saint Martin exhibit multiple resistance to organophosphates (temephos and malathion), and pyrethroids
Khan, Hafiz Azhar Ali; Akram, Waseem; Shad, Sarfraz Ali; Lee, Jong-Jin
House flies, Musca domestica L., are important pests of dairy operations worldwide, with the ability to adapt wide range of environmental conditions. There are a number of insecticides used for their management, but development of resistance is a serious problem. Insecticide mixtures could enhance the toxicity of insecticides in resistant insect pests, thus resulting as a potential resistance management tool. The toxicity of bifenthrin, cypermethrin, deltamethrin, chlorpyrifos, profenofos, emamectin benzoate and fipronil were assessed separately, and in mixtures against house flies. A field-collected population was significantly resistant to all the insecticides under investigation when compared with a laboratory susceptible strain. Most of the insecticide mixtures like one pyrethroid with other compounds evaluated under two conditions (1∶1-“A” and LC50: LC50-“B”) significantly increased the toxicity of pyrethroids in the field population. Under both conditions, the combination indices of pyrethroids with other compounds, in most of the cases, were significantly below 1, suggesting synergism. The enzyme inhibitors, PBO and DEF, when used in combination with insecticides against the resistant population, toxicities of bifenthrin, cypermethrin, deltamethrin and emamectin were significantly increased, suggesting esterase and monooxygenase based resistance mechanism. The toxicities of bifenthrin, cypermethrin and deltamethrin in the resistant population of house flies could be enhanced by the combination with chlorpyrifos, profenofos, emamectin and fipronil. The findings of the present study might have practical significance for resistance management in house flies. PMID:23613758
Full Text Available PURPOSE: The DNA methylation inhibitor 5-aza-2'-deoxycytidine (DAC is approved for the treatment of myelodysplastic syndromes (MDS, but resistance to DAC develops during treatment and mechanisms of resistance remain unknown. Therefore, we investigated mechanisms of primary and secondary resistance to DAC in MDS. PATIENTS AND METHODS: We performed Quantitative Real-Time PCR to examine expression of genes related to DAC metabolism prior to therapy in 32 responders and non-responders with MDS as well as 14 patients who achieved a complete remission and subsequently relapsed while on therapy (secondary resistance. We then performed quantitative methylation analyses by bisulfite pyrosequencing of 10 genes as well as Methylated CpG Island Amplification Microarray (MCAM analysis of global methylation in secondary resistance. RESULTS: Most genes showed no differences by response, but the CDA/DCK ratio was 3 fold higher in non-responders than responders (P<.05, suggesting that this could be a mechanism of primary resistance. There were no significant differences at relapse in DAC metabolism genes, and no DCK mutations were detected. Global methylation measured by the LINE1 assay was lower at relapse than at diagnosis (P<.05. On average, the methylation of 10 genes was lower at relapse (16.1% compared to diagnosis (18.1% (P<.05. MCAM analysis showed decreased methylation of an average of 4.5% (range 0.6%-9.7% of the genes at relapse. By contrast, new cytogenetic changes were found in 20% of patients. CONCLUSION: Pharmacological mechanisms are involved in primary resistance to DAC, whereas hypomethylation does not prevent a relapse for patients with DAC treatment.
Rius, Marc; Potter, Elaine E; Aguirre, J David; Stachowicz, John J
Biotic resistance is the ability of communities to inhibit the establishment, spread or impact of novel species. However, the interactions that underlie biotic resistance depend heavily on the contexts in which species interact. Consequently, studies of biotic resistance that consider single processes, patches, species or life-history stages may provide an incomplete picture of the capacity for communities to resist invasion. Many organisms have multiphasic life cycles, where individuals can occupy distinct niches at different stages of the life history. Generally, studies of biotic resistance focus on interactions within a single life-history stage, and interactions at other life-history stages are overlooked. Here, we demonstrate that different mechanisms of biotic resistance occur across the life history and together limit the invasion success of an introduced marine invertebrate (Ciona intestinalis) in Northern California. We tested the role of interactions (competition and predation) with the resident community in limiting the abundance of Ciona through experiments conducted on fertilization, larval survival, settlement, early postsettlement survival, and the survival of juveniles and adults. Under some circumstances, Ciona became abundant in mid-successional stages and showed more rapid growth rates than a morphologically similar native species, Ascidia ceratodes. However, predators reduced Ciona abundance much more than that of Ascidia at several life stages. Furthermore, Ciona appeared to be a weaker competitor at the adult stage. Early life-history interactions with other sessile species at the fertilization, larval and recruit stages had modest to no effects on Ciona abundance. The presence of biotic resistance mechanisms acting at multiple life stages, and potentially under different conditions, suggests that different components of biotic resistance interact to enhance the resident community's resistance to invasion.
Kim, Young-Joon; Lee, Si-Hyeock; Lee, Si-Woo; Ahn, Young-Joon
A field colony of the Two-spotted spider mite, Tetranychus urticae (Koch), resistant to fenpyroximate was further selected with fenpyroximate 5SC for 20 generations at a selection pressure of 30-50% mortality (designated as FR-20 strain). Resistance and cross-resistance levels of the FR-20 strain to 18 acaricides were determined using a spray method. The FR-20 strain was extremely resistant to fenpyroximate [resistance ratio (RR) 252]. The strain exhibited extremely strong positive cross-resistance to acrinathrin (RR 196), and high levels of resistance to benzoximate (RR 55) and propargite (RR 64). Moderate levels of cross-resistance (RR 11-40) to abamectin, fenbutatin oxide, fenpropathrin, pyridaben, pyridaben + bifenthrin and tebufenpyrad were observed. The FR-20 strain showed low levels of resistance (RR fenazaquin and milbemectin. Synergist experiments with different metabolic inhibitors revealed that piperonyl butoxide had the greatest effect on the efficacy of fenpyroximate, followed by iprobenfos and triphenyl phosphate. In a comparative assay with detoxifying enzymes, the FR-20 strain showed 2.5-fold higher activity in p-nitroanisole-O-demethylation, and 2.5- and 2.2-fold higher activities in alpha- and beta-naphthyl acetate hydrolysis, respectively. These results suggested that enhanced activities of both mixed-function oxidases and esterases likely contribute to the fenpyroximate resistance of the FR-20 strain of T urticae.
Full Text Available Abstract Background Cytochrome P450 enzymes (P450s have been implicated in insecticide resistance. Anopheles minumus mosquito P450 isoforms CYP6AA3 and CYP6P7 are capable of metabolizing pyrethroid insecticides, however CYP6P8 lacks activity against this class of compounds. Findings Homology models of the three An. minimus P450 enzymes were constructed using the multiple template alignment method. The predicted enzyme model structures were compared and used for molecular docking with insecticides and compared with results of in vitro enzymatic assays. The three model structures comprise common P450 folds but differences in geometry of their active-site cavities and substrate access channels are prominent. The CYP6AA3 model has a large active site allowing it to accommodate multiple conformations of pyrethroids. The predicted CYP6P7 active site is more constrained and less accessible to binding of pyrethroids. Moreover the predicted hydrophobic interface in the active-site cavities of CYP6AA3 and CYP6P7 may contribute to their substrate selectivity. The absence of CYP6P8 activity toward pyrethroids appears to be due to its small substrate access channel and the presence of R114 and R216 that may prevent access of pyrethroids to the enzyme heme center. Conclusions Differences in active site topologies among CYPAA3, CYP6P7, and CYP6P8 enzymes may impact substrate binding and selectivity. Information obtained using homology models has the potential to enhance the understanding of pyrethroid metabolism and detoxification mediated by P450 enzymes.
Gaines, Todd A; Shaner, Dale L; Ward, Sarah M; Leach, Jan E; Preston, Christopher; Westra, Philip
Evolved glyphosate resistance in weedy species represents a challenge for the continued success and utility of glyphosate-resistant crops. Glyphosate functions by inhibiting the plant enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). The resistance mechanism was determined in a population of glyphosate-resistant Palmer amaranth from Georgia (U.S.). Within this population, glyphosate resistance correlates with increases in (a) genomic copy number of EPSPS, (b) expression of the EPSPS transcript, (c) EPSPS protein level, and (d) EPSPS enzymatic activity. Dose response results from the resistant and an F(2) population suggest that between 30 and 50 EPSPS genomic copies are necessary to survive glyphosate rates between 0.5 and 1.0 kg ha(-1). These results further confirm the role of EPSPS gene amplification in conferring glyphosate resistance in this population of Palmer amaranth. Questions remain related to how the EPSPS amplification initially occurred and the occurrence of this mechanism in other Palmer amaranth populations and other glyphosate-resistant species.
Gurevitz, J. M.; Gaspe, M. S.; Enríquez, G. F.; Vassena, C. V.; Alvarado-Otegui, J. A.; Provecho, Y. M.; Mougabure Cueto, G. A; Picollo, M. I.; Kitron, U.; Gürtler, R. E.
Effectiveness of the elimination efforts against Triatoma infestans (Klug) in South America through residual application of pyrethroid insecticides has been highly variable in the Gran Chaco region. We investigated apparent vector control failures after a standard community-wide spraying with deltamethrin SC in a rural area of northeastern Argentina encompassing 353 houses. Insecticide spraying reduced house infestation less than expected: from 49.5% at baseline to 12.3 and 6.7% at 4 and 8 mo postspraying, respectively. Persistent infestations were detected in 28.4% of houses, and numerous colonies with late-stage bugs were recorded after the interventions. Laboratory bioassays showed reduced susceptibility to pyrethroids in the local bug populations. Eleven of 14 bug populations showed reduced mortality in diagnostic dose assays (range, 35 ± 5% to 97 ± 8%) whereas the remainder had 100% mortality. A fully enclosed residual bug population in a large chicken coop survived four pyrethroid sprays, including two double-dose applications, and was finally suppressed with malathion. The estimated resistance ratio of this bug population was 7.17 (range, 4.47–11.50). Our field data combined with laboratory bioassays and a residual foci experiment demonstrate that the initial failure to suppress T. infestans was mainly because of the unexpected occurrence of reduced susceptibility to deltamethrin in an area last treated with pyrethroid insecticides 12 yr earlier. Our results underline the need for close monitoring of the impact of insecticide spraying to provide early warning of possible problems due to enhanced resistance or tolerance and determine appropriate responses. PMID:23270166
Full Text Available Since the concept of pathogen derived resistance (PDR was proposed in 1985, genetic transformation of plants to express virus-derived sequences has been used to engineer resistance to many viruses. This paper reviews PDR approaches to Potato virus Y (PVY, type member of the genus Potyvirus. PDR to viruses operates often through RNA-mediated resistance mechanisms that do not require protein expression. Studies on the RNA-mediated resistance have led to the discovery of post-transcriptional gene silencing (PTGS, a mechanism that controls gene expression in eukaryotic cells and provides natural protection against virus infections. Viruses, in turn, can suppress the PTGS with some of their proteins, such as the helper component-proteinase protein of PVY. Expression of PVY proteins in transgenic plants entails a risk for heterologous encapsidation or synergism with viruses that infect the PVY-resistant transgenic plant. These risks are avoided using RNA-mediated resistance, but a risk still exists for recombination between the transgene transcript and the RNA genome of the infecting virus, which may create a virus with altered properties. The harmful consequences can be limited to some extent by removing functional motifs from the viral sequence used as a transgene.;
Chang, Yao-Feng; Fowler, Burt; Chen, Ying-Chen; Zhou, Fei; Wu, Xiaohan; Chen, Yen-Ting; Wang, Yanzhen; Xue, Fei; Lee, Jack C.
Intrinsic unipolar SiOx-based resistance random access memories (ReRAM) characterization, switching mechanisms, and applications have been investigated. Device structures, material compositions, and electrical characteristics are identified that enable ReRAM cells with high ON/OFF ratio, low static power consumption, low switching power, and high readout-margin using complementary metal-oxide semiconductor transistor (CMOS)-compatible SiOx-based materials. These ideas are combined with the use of horizontal and vertical device structure designs, composition optimization, electrical control, and external factors to help understand resistive switching (RS) mechanisms. Measured temperature effects, pulse response, and carrier transport behaviors lead to compact models of RS mechanisms and energy band diagrams in order to aid the development of computer-aided design for ultralarge-v scale integration. This chapter presents a comprehensive investigation of SiOx-based RS characteristics and mechanisms for the post-CMOS device era.
Ling, Shanfeng; Zhang, Runjie
The resistant (R) strain of the planthopper Nilaparvata lugens (Stål) selected for bisultap resistance displayed 7.7-fold resistance to bisultap and also had cross-resistance to nereistoxin (monosultap, thiocyclam, and cartap), chlorpyrifos, dimethoate, and malathion but no cross-resistance to buprofezin, imidacloprid, and fipronil. To find out the biochemical mechanism of resistance to bisultap, biochemical assay was done. The results showed that cytochrome P450 monooxygenases (P450) activity in R strain was 2.71-fold that in susceptible strain (S strain), in which the changed activity for general esterase (EST) was 1.91 and for glutathione S-transferases only 1.32. Piperonyl butoxide (PBO) could significantly inhibit P450 activity (percentage of inhibition [PI]: 37.31%) in the R strain, with ESTs PI = 16.04% by triphenyl phosphate (TPP). The results also demonstrated that diethyl maleate had no synergism with bisultap. However, PBO displayed significant synergism in three different strains, and the synergism increased with resistance (S strain 1.42, Lab strain, 2.24 and R strain, 3.23). TPP also showed synergism for three strains, especially in R strain (synergistic ratio = 2.47). An in vitro biochemical study and in vivo synergistic study indicated that P450 might be play important role in the biochemical mechanism of bisultap resistance and that esterase might be the important factor of bisultap resistance. Acetylcholinesterase (AChE) insensitivity play important role in bisultap resistance. We suggest that buprofezin, imidacloprid, and fipronil could be used in resistance management programs for N. lugens via alternation and rotation with bisultap.
Philbert, Anitha; Lyantagaye, Sylvester Leonard; Pradel, Gabriele; Ngwa, Che Julius; Nkwengulila, Gamba
To assess the susceptibility status of malaria vectors to pyrethroids and dichlorodiphenyltrichloroethane (DDT), characterise the mechanisms underlying resistance and evaluate the role of agro-chemical use in resistance selection among malaria vectors in Sengerema agro-ecosystem zone, Tanzania. Mosquito larvae were collected from farms and reared to obtain adults. The susceptibility status of An. gambiae s.l. was assessed using WHO bioassay tests to permethrin, deltamethrin, lambdacyhalothrin, etofenprox, cyfluthrin and DDT. Resistant specimens were screened for knock-down resistance gene (kdr), followed by sequencing both Western and Eastern African variants. A gas chromatography-mass spectrophotometer (GC-MS) was used to determine pesticide residues in soil and sediments from mosquitoes' breeding habitats. Anopheles gambiae s.l. was resistant to all the insecticides tested. The population of Anopheles gambiae s.l was composed of Anopheles arabiensis by 91%. The East African kdr (L1014S) allele was found in 13 of 305 specimens that survived insecticide exposure, with an allele frequency from 0.9% to 50%. DDTs residues were found in soils at a concentration up to 9.90 ng/g (dry weight). The observed high resistance levels of An. gambiae s.l., the detection of kdr mutations and pesticide residues in mosquito breeding habitats demonstrate vector resistance mediated by pesticide usage. An integrated intervention through collaboration of agricultural, livestock and vector control units is vital. © 2017 John Wiley & Sons Ltd.
Full Text Available Antibiotic resistance in Helicobacter pylori (H. pylori is the main factor affecting the efficacy of current treatment methods against infection caused by this organism. The traditional culture methods for testing bacterial susceptibility to antibiotics are expensive and require 10 to 14 days. Since resistance to clarithromycin, fluoroquinolone, and tetracycline seems to be exclusively caused by specific mutations in a small region of the responsible gene, molecular methods offer an attractive alternative to the above-mentioned techniques. The technique of polymerase chain reaction (PCR is an accurate and rapid method for the detection of mutations that confer antibiotic resistance. This review highlights the mechanisms of antibiotic resistance in H. pylori and the molecular methods for antibiotic susceptibility testing.
Samuel, Varman T; Petersen, Kitt Falk; Shulman, Gerald I
Insulin resistance has long been associated with obesity. More than 40 years ago, Randle and colleagues postulated that lipids impaired insulin-stimulated glucose use by muscles through inhibition of glycolysis at key points. However, work over the past two decades has shown that lipid-induced insulin resistance in skeletal muscle stems from defects in insulin-stimulated glucose transport activity. The steatotic liver is also resistant to insulin in terms of inhibition of hepatic glucose production and stimulation of glycogen synthesis. In muscle and liver, the intracellular accumulation of lipids—namely, diacylglycerol—triggers activation of novel protein kinases C with subsequent impairments in insulin signalling. This unifying hypothesis accounts for the mechanism of insulin resistance in obesity, type 2 diabetes, lipodystrophy, and ageing; and the insulin-sensitising effects of thiazolidinediones. PMID:20609972
de Carvalho, Leonardo Bianco; Alves, Pedro Luis da Costa Aguiar; González-Torralva, Fidel; Cruz-Hipolito, Hugo Enrique; Rojano-Delgado, Antonia María; De Prado, Rafael; Gil-Humanes, Javier; Barro, Francisco; de Castro, María Dolores Luque
Digitaria insularis biotypes resistant to glyphosate have been detected in Brazil. Studies were carried out in controlled conditions to determine the role of absorption, translocation, metabolism, and gene mutation as mechanisms of glyphosate resistance in D. insularis. The susceptible biotype absorbed at least 12% more (14)C-glyphosate up to 48 h after treatment (HAT) than resistant biotypes. High differential (14)C-glyphosate translocation was observed at 12 HAT, so that >70% of the absorbed herbicide remained in the treated leaf in resistant biotypes, whereas 42% remained in the susceptible biotype at 96 HAT. Glyphosate was degraded to aminomethylphosphonic acid (AMPA), glyoxylate, and sarcosine by >90% in resistant biotypes, whereas a small amount of herbicide (up to 11%) was degraded by the susceptible biotype up to 168 HAT. Two amino acid changes were found at positions 182 and 310 in EPSPS, consisting of a proline to threonine and a tyrosine to cysteine substitution, respectively, in resistant biotypes. Therefore, absorption, translocation, metabolism, and gene mutation play an important role in the D. insularis glyphosate resistance.
Pyrethroid insecticides produce acute neurotoxicity in mammals. According to the FQPA mandate, the USEPA is required to consider the risk of cumulative toxicity posed to humans through exposure to pyrethroid mixtures. Thermoregulatory response (TR) is being used to determine if t...
In the past years, several agents targeting signaling proteins critical for breast cancer growth and dissemination entered clinical evaluation. They include drugs directed against the HER/ErbB family of receptor tyrosine kinases, especially HER2; several downstream signal transducers; and proteins involved in tumor angiogenesis and dissemination. Unfortunately, resistance to targeted agents is a quite common feature, and understanding of the molecular mechanisms predicting response or failure has become a crucial issue to optimize treatment and select patients who are the best candidates to respond. The neoadjuvant setting offers unique opportunities allowing tumor sampling and search for molecular determinants of response. A variety of tumor and host factors may account for the onset of resistance. Major progress has been made in the understanding of the mechanisms involved in the primary and acquired resistance to targeted agents, especially the anti-HER2 drugs, which play a pivotal role in the weaponry against breast cancer.
Yang, Wen-Chi; Lin, Sheng-Fung
Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients eventually relapse or become refractory to current treatments. Although the treatments have improved, the major problem in MM is resistance to therapy. Clonal evolution of MM cells and bone marrow microenvironment changes contribute to drug resistance. Some mechanisms affect both MM cells and microenvironment, including the up- and downregulation of microRNAs and programmed death factor 1 (PD-1)/PD-L1 interaction. Here, we review the pathogenesis of MM cells and bone marrow microenvironment and highlight possible drug resistance mechanisms. We also review a potential molecular targeting treatment and immunotherapy for patients with refractory or relapse MM. PMID:26649299
Full Text Available Haiyan Zhu, Hui Luo, Wenwen Zhang, Zhaojun Shen, Xiaoli Hu, Xueqiong Zhu Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. Keywords: cisplatin, epithelial–mesenchymal transition, microRNA, molecular mechanism, resistance
Full Text Available Purpose: To analyze the resistance mechanisms in Acinetobacter species by phenotypic methods. Methods: Antibiotic susceptibility profile for 150 clinical isolates of Acinetobacte r was determined by the standard disk diffusion method. Isolates detected to be meropenem resistant were tested further by broth microdilution minimum inhibitory concentration (MIC for meropenem. The resistant isolates were also tested for metallo β -lactamase (MBL production by the double-disk approximation test, for AmpC beta-lactamase production and efflux pump detection by agar microdilution MIC with and without reserpine. Results: Twenty-one isolates were found resistant to meropenem by the standard disk diffusion method. Nine samples were from patients admitted in intensive care units (ICUs. Broth microdilution MICs of the isolates revealed low-level resistance to meropenem. MBL was not produced by any of these isolates. AmpC β -lactamases were produced by nine (43% isolates. ′Efflux pump′-mediated resistance to meropenem was detected in two out of nine random isolates tested for the same . Conclusions: Carbapenem resistance is not uncommon in Acinetobacter isolates. AmpC production may cause carbapenem resistance. MBL and efflux pump may not be important causes of carbapenem resistance.
Wasyl, Dariusz; Hoszowski, Andrzej; Zając, Magdalena
The study was focused on characterisation of quinolone resistance mechanisms in Salmonella isolated from animals, food, and feed between 2008 and 2011. Testing of Minimal Inhibitory Concentrations revealed 6.4% of 2680 isolates conferring ciprofloxacin resistance. Simultaneously 37.7% and 40.8% were accounted for, respectively, nalidixic acid and ciprofloxacin Non Wild-Type populations. Amplification and sequencing of quinolone resistance determining region of topoisomerases genes in 44 isolates identified multiple amino-acid substitutions in gyrA at positions Ser83 (N=22; → Leu, → Phe, → Tyr), Asp87 (N=22; → Asn, → Gly, → Tyr) and parC (Thr57Ser, N=23; Ala141Ser, N=1). No relevant mutations were identified in gyrB and parE. Twelve patterns combining one or two substitutions were related to neither serovar nor ciprofloxacin MIC. In 92 isolates suspected for plasmid mediated quinolone resistance two qnr alleles were found: qnrS1 (or qnrS3; N=50) and qnrB19 (or qnrB10; N=24). Additionally, two isolates with chromosomally encoded mechanisms carried qnrS1 and qnrS2. All tested isolates were negative for qnrA, qnrC, qnrD, qepA, aac(6')-Ib-cr. Both chromosomal and plasmid mediated quinolone resistance determinants were found in several Salmonella serovars and Pulsed Field Gel Electrophoresis was used to assess phylogenetic similarity of selected isolates (N=82). Salmonella Newport was found to accumulate quinolone resistance determinants and the serovar was spreading clonally with either variable gyrA mutations, qnrS1/S3, or qnrB10/B19. Alternatively, various determinants are dispersed among related S. Enteritidis isolates. Antimicrobial selection pressure, multiple resistance determinants and scenarios for their acquisition and spread make extremely difficult to combat quinolone resistance.
Kemerink, M.; Asadi, K.; Blom, P.W.M.; Leeuw, D.M. de
The availability of a reliable memory element is crucial for the fabrication of 'plastic' logic circuits. We use numerical simulations to show that the switching mechanism of ferroelectric-driven organic resistive switches is the stray field of the polarized ferroelectric phase. The stray field modu
Sietsma, H; Dijkhuis, AJ; Kamps, W; Kok, JW
Disseminated neuroblastoma usually calls for chemotherapy as the primary approach for treatment. Treatment failure is often attributable to drug resistance. This involves a variety of cellular mechanisms, including increased drug efflux through expression of ATP-binding cassette transporters (e.g.,
Full Text Available Triatomine insects are vectors of Trypanosoma cruzi, a protozoan parasite that is the causative agent of Chagas' disease. This is a neglected disease affecting approximately 8 million people in Latin America. The existence of diverse pyrethroid resistant populations of at least two species demonstrates the potential of triatomines to develop high levels of insecticide resistance. Therefore, the incorporation of strategies for resistance management is a main concern for vector control programs. Three enzymatic superfamilies are thought to mediate xenobiotic detoxification and resistance: Glutathione Transferases (GSTs, Cytochromes P450 (CYPs and Carboxyl/Cholinesterases (CCEs. Improving our knowledge of key triatomine detoxification enzymes will strengthen our understanding of insecticide resistance processes in vectors of Chagas' disease.The discovery and description of detoxification gene superfamilies in normalized transcriptomes of three triatomine species: Triatoma dimidiata, Triatoma infestans and Triatoma pallidipennis is presented. Furthermore, a comparative analysis of these superfamilies among the triatomine transcriptomes and the genome of Rhodnius prolixus, also a triatomine vector of Chagas' disease, and other well-studied insect genomes was performed. The expression pattern of detoxification genes in R. prolixus transcriptomes from key organs was analyzed. The comparisons reveal gene expansions in Sigma class GSTs, CYP3 in CYP superfamily and clade E in CCE superfamily. Moreover, several CYP families identified in these triatomines have not yet been described in other insects. Conversely, several groups of insecticide resistance related enzymes within each enzyme superfamily are reduced or lacking in triatomines. Furthermore, our qRT-PCR results showed an increase in the expression of a CYP4 gene in a T. infestans population resistant to pyrethroids. These results could point to an involvement of metabolic detoxification mechanisms
Traverso, Lucila; Lavore, Andrés; Sierra, Ivana; Palacio, Victorio; Martinez-Barnetche, Jesús; Latorre-Estivalis, José Manuel; Mougabure-Cueto, Gaston; Francini, Flavio; Lorenzo, Marcelo G.; Rodríguez, Mario Henry; Ons, Sheila; Rivera-Pomar, Rolando V.
detoxification mechanisms on the high levels of pyrethroid resistance detected in triatomines from the Gran Chaco ecoregion. Conclusions and significance Our results help to elucidate the potential insecticide resistance mechanisms in vectors of Chagas’ disease and provide new relevant information for this field. This study shows that metabolic resistance might be a contributing cause of the high pyrethroid resistance observed in wild T. infestans populations from the Gran Chaco ecoregion, area in which although subjected to intense pyrethroid treatments, vector control has failed. This study opens new avenues for further functional studies on triatomine detoxification mechanisms. PMID:28199333
Byberg, J R; Jørgensen, Flemming Steen; Klemmensen, P D
. These pharmacophores are based on the relationship between molecular structure and biological activity for a number of pyrethroid esters. The pharmacophores, which describe the relative location in space of the unsaturated systems, the dimethyl groups and the ester moiety, may be useful in the design of novel...
Andersson, D I; Hughes, D; Kubicek-Sutherland, J Z
Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings.
Full Text Available BACKGROUND: Resistance to triazoles was recently reported in Aspergillus fumigatus isolates cultured from patients with invasive aspergillosis. The prevalence of azole resistance in A. fumigatus is unknown. We investigated the prevalence and spread of azole resistance using our culture collection that contained A. fumigatus isolates collected between 1994 and 2007. METHODS AND FINDINGS: We investigated the prevalence of itraconazole (ITZ resistance in 1,912 clinical A. fumigatus isolates collected from 1,219 patients in our University Medical Centre over a 14-y period. The spread of resistance was investigated by analyzing 147 A. fumigatus isolates from 101 patients, from 28 other medical centres in The Netherlands and 317 isolates from six other countries. The isolates were characterized using phenotypic and molecular methods. The electronic patient files were used to determine the underlying conditions of the patients and the presence of invasive aspergillosis. ITZ-resistant isolates were found in 32 of 1,219 patients. All cases were observed after 1999 with an annual prevalence of 1.7% to 6%. The ITZ-resistant isolates also showed elevated minimum inhibitory concentrations of voriconazole, ravuconazole, and posaconazole. A substitution of leucine 98 for histidine in the cyp51A gene, together with two copies of a 34-bp sequence in tandem in the gene promoter (TR/L98H, was found to be the dominant resistance mechanism. Microsatellite analysis indicated that the ITZ-resistant isolates were genetically distinct but clustered. The ITZ-sensitive isolates were not more likely to be responsible for invasive aspergillosis than the ITZ-resistant isolates. ITZ resistance was found in isolates from 13 patients (12.8% from nine other medical centres in The Netherlands, of which 69% harboured the TR/L98H substitution, and in six isolates originating from four other countries. CONCLUSIONS: Azole resistance has emerged in A. fumigatus and might be more
Xia, Jufeng; Gao, Jianjun; Tang, Wei
Nosocomial infection is a kind of infection, which is spread in various hospital environments, and leads to many serious diseases (e.g. pneumonia, urinary tract infection, gastroenteritis, and puerperal fever), and causes higher mortality than community-acquired infection. Bacteria are predominant among all the nosocomial infection-associated pathogens, thus a large number of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and carbapenems, are adopted in clinical treatment. However, in recent years antibiotic resistance quickly spreads worldwide and causes a critical threat to public health. The predominant bacteria include Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. In these bacteria, resistance emerged from antibiotic resistant genes and many of those can be exchanged between bacteria. With technical advances, molecular mechanisms of resistance have been gradually unveiled. In this review, recent advances in knowledge about mechanisms by which (i) bacteria hydrolyze antibiotics (e.g. extended spectrum β-lactamases, (ii) AmpC β-lactamases, carbapenemases), (iii) avoid antibiotic targeting (e.g. mutated vanA and mecA genes), (iv) prevent antibiotic permeation (e.g. porin deficiency), or (v) excrete intracellular antibiotics (e.g. active efflux pump) are summarized.
Abel, E. Dale; O'Shea, Karen M.; Ramasamy, Ravichandran
Insulin resistance is a characteristic feature of obesity and Type 2 diabetes and impacts the heart in various ways. Impaired insulin-mediated glucose uptake is a uniformly observed characteristic of the heart in these states, although changes in upstream kinase signaling are variable and dependent on the severity and duration of the associated obesity or diabetes. The understanding of the physiological and pathophysiological role of insulin resistance in the heart is evolving. To maintain its high energy demands, the heart is capable of utilizing many metabolic substrates. Although, insulin signaling may directly regulate cardiac metabolism, its main role is likely the regulation of substrate delivery from the periphery to the heart. In addition to promoting glucose uptake, insulin regulates long chain fatty acid uptake, protein synthesis, and vascular function in the normal cardiovascular system. Recent advances in understanding the role of metabolic, signaling, and inflammatory pathways in obesity have provided opportunities to better understand the pathophysiology of insulin resistance in the heart. This review will summarize our current understanding of metabolic mechanisms for and consequences of insulin resistance in the heart and discuss potential new areas for investigating novel mechanisms that contribute to insulin resistance in the heart. PMID:22895668
Claudio D. Miranda
Full Text Available Consumer demand for affordable fish drives the ever-growing global aquaculture industry. The intensification and expansion of culture conditions in the production of several finfish species has been coupled with an increase in bacterial fish disease and the need for treatment with antimicrobials. Understanding the molecular mechanisms of antimicrobial resistance prevalent in aquaculture environments is important to design effective disease treatment strategies, to prioritize the use and registration of antimicrobials for aquaculture use, and to assess and minimize potential risks to public health. In this brief article we provide an overview of the molecular mechanisms of antimicrobial resistance mechanisms in finfish aquaculture environments and highlight specific research that should provide the basis of sound, science-based policies for the use of antimicrobials in aquaculture.
Coleman, David C
Candida dubliniensis was first described in 1995 and is the most closely related species to the predominant human fungal pathogen Candida albicans. C. dubliniensis is significantly less prevalent and less pathogenic than C. albicans and is primarily associated with infections in HIV-infected individuals and other immunocompromised cohorts. The population structure of C. dubliniensis consists of three well-defined major clades and is significantly less diverse than C. albicans. The majority of C. dubliniensis isolates are susceptible to antifungal drugs commonly used to treat Candida infections. To date only two major patterns of antifungal drug resistance have been identified and the molecular mechanisms of these are very similar to the resistance mechanisms that have been described previously in C. albicans. However, significant differences are evident in the predominant antifungal drug mechanisms employed by C. dubliniensis, differences that reflect its more clonal nature, its lower prevalence and characteristics of its genome, the complete sequence of which has only recently been determined.
Wu, Pei; Zhang, Wenqi; Bay, Niels
The dynamic mechanical properties of a resistance welding machine have significant influence on weld quality, which must be considered when simulating the welding process numerically. However, due to the complexity of the machine structure and the mutual coupling of components of the machine system...... characterizing the dynamic mechanical characteristics of resistance welding machines is suggested, and a test set-up is designed determining the basic, independent machine parameters required in the model. The model is verified by performing a series of mechanical tests as well as real projection welds......., it is very difficult to measure or calculate the basic, independent machine parameters required in a mathematical model of the machine dynamics, and no test method has so far been presented in literature, which can be applied directly in an industrial environment. In this paper, a mathematical model...
Wu, Pei; Zhang, Wenqi; Bay, Niels
The dynamic mechanical properties of a resistance welding machine have significant influence on weld quality, which must be considered when simulating the welding process numerically. However, due to the complexity of the machine structure and the mutual coupling of components of the machine system......, it is very difficult to measure or calculate the basic, independent machine parameters required in a mathematical model of the machine dynamics, and no test method has so far been presented in literature, which can be applied directly in an industrial environment. In this paper, a mathematical model...... characterizing the dynamic mechanical characteristics of resistance welding machines is suggested, and a test set-up is designed determining the basic, independent machine parameters required in the model. The model is verified by performing a series of mechanical tests as well as real projection welds....
Wu, Pei; Zhang, Wenqi; Bay, Niels
Mechanical dynamic responses of resistance welding machine have a significant influence on weld quality and electrode service life, it must be considered when the real welding production is carried out or the welding process is simulated. The mathematical models for characterizing the mechanical...... to the complexities and differences of machine constructions. In this paper, a method of identifying the machine mechanical parameters based on the measured data is presented no matter how the machine construction and what types of machine are. The computations are implemented in MATLAB....
Wu, Pei; Zhang, Wenqi; Bay, Niels
Mechanical dynamic responses of resistance welding machine have a significant influence on weld quality and electrode service life, it must be considered when the real welding production is carried out or the welding process is simulated. The mathematical models for characterizing the mechanical...... to the complexities and differences of machine constructions. In this paper, a method of identifying the machine mechanical parameters based on the measured data is presented no matter how the machine construction and what types of machine are. The computations are implemented in MATLAB....
谢佐福; 周冬梅; 林贤东; 林声; 吴允昆
Objective: To understand whether verapamil (VER) resistance development in the multidrug-resistant cell line and its mechanism. Methods: K562/ADM/VER cell subline resistant to verapamil was established through a gradual increase of VER concentration in the media. MTT method was used to assay resistance to VER, cross resistance to dipyriamole (DPM), cyclosporin A (CsA) in the cells, and HPLC and spectrofluorometer to detect intracellular accumulation of VER or ADM respectively, as well as S-P immunocytochemical technique for detection of genes expression. Results: It were observed that 7.9-fold increase in VER resistance, significantly reduced intracellular accumulation of VER or ADM and also develop across resistance to DPM and CsA in K562/ADM/VER cells, compared with its parent cell, K562/ADM. High-level of p-glycoprotein(pgp), middle-level of p53, p16, was present in two cell lines without expression of GSTPI, C-myc, C-myc, C-fos and C-erbB-2. Bc1-2 protein expression was found only in K562/ADM cells. Conclusion: K562/ADM cells were capable of being induced to develop resistance to VER.
Sakagami, Y; Yokoyama, H; Nishimura, H; Ose, Y; Tashima, T
The mechanisms of resistance of Pseudomonas aeruginosa to benzalkonium chloride (BC) were studied. The effluence of cell components was observed in susceptible P. aeruginosa by electron microscopy, but resistant P. aeruginosa seemed to be undamaged. No marked changes in cell surface potential between Escherichia coli NIHJC-2 and a spheroplast strain were found. The contents of phospholipids (PL) and fatty and neutral lipids (FNL) in the cell walls of resistant P. aeruginosa were higher than those in the cell walls of susceptible P. aeruginosa. The amounts of BC adsorbed to PL and FNL of cell walls of BC-resistant P. aeruginosa were lower than those for BC-susceptible P. aeruginosa. Fifteen species of cellular fatty acids were identified by capillary gas chromatography and gas chromatography-mass spectrometry. The ability of BC to permeate the cell wall was reduced because of the increase in cellular fatty acids. These results suggested that the resistance of P. aeruginosa to BC is mainly a result of increased in the contents of PL and FNL. In resistant P. aeruginosa, the decrease in the amount of BC adsorbed is likely to be the result of increases in the contents of PL and FNL. Images PMID:2506813
Chen, Zihao; Gao, Tao; Liang, Shuping; Liu, Kexue; Zhou, Mingguo; Chen, Changjun
Although carbendazim (MBC) and other benzimidazole fungicides have effectively controlled bakanae disease of rice (which is caused by Fusarium fujikuroi, F. proliferatum, and F. verticillioides) in the past, MBC resistance has become common. Previous research has shown that MBC resistance results from a mutation in the β1 -tubulin (β1 tub) gene in F. verticillioides. However, MBC resistance in F. fujikuroi, a predominant species in China, does not result from a mutation in the β1 tub. The molecular mechanism of F. fujikuroi resistance against benzimidazole fungicides is poorly understood. In this study, we determined that although β1 tub and β2 -tubulin (β2 tub) in F. fujikuroi have high homology with β1 tub and β2 tub in F. verticillioides, MBC resistance in F. fujikuroi results from mutations in β2 tub [GAG(Glu)→GTG(Val) at codon 198, TTC(Phe)→TAC(Tyr) at codon 200, and GGC(Gly)→GGT(Gly) at codon 235] but not in β1 tub. Δβ2 tub (β2 tub deletion) mutants were highly sensitive to MBC, produced fewer conidia and were less virulent than parental strains. Complementation of the Δβ2 tub mutants with a copy of the whole β2 tub locus from their parental strains restored the level of MBC resistance (or sensitivity) to that of the parental strain.
Chand, Saswati; O'Hayer, Kevin; Blanco, Fernando F; Winter, Jordan M; Brody, Jonathan R
Pancreatic cancer (pancreatic ductal adenocarcinoma, PDA) is infamously moving to the top of the list as one of the most lethal cancers with an overall 5 year survival rate of 7%. Multiple genomic-based and molecular characterization studies of PDA specimens and established animal models have provided the field with multiple targets and a progression model of this disease. Still, to date, the best therapeutic options are surgery and combination cytotoxic therapies. In general, even in the best case scenario (i.e., an early stage diagnosis and a response to a specific therapy), most of these fortunate patients' PDA cells acquire or exert resistance mechanisms and eventually kill the patient. Herein, we touch on a growing field of investigation that focuses on PDA cell therapeutic resistance mechanisms. We examine extrinsic elements (i.e., the tumor microenvironment, hypoxia) to the intrinsic processes within the cell (i.e., post-transcriptional gene regulation and somatic mutations) that are important for therapeutic efficacy and resistance. Even as better targeted and personalized approaches move through the clinical trial pipeline the discussed resistance mechanisms will most likely play a role in the management of this deadly disease.
Girardello, Raquel; Visconde, Marina; Cayô, Rodrigo; Figueiredo, Regina Célia Bressan Queiroz de; Mori, Marcelo Alves da Silva; Lincopan, Nilton; Gales, Ana Cristina
Polymyxins have become drugs of last resort for treatment of multi-drug resistant (MDR) Gram-negative infections. However, the mechanisms of resistance to this compound have not been completely elucidated. In this study, we evaluated the mechanisms of resistance to this antimicrobial in two A. baumannii clinical isolates, respectively, susceptible (A027) and resistant (A009) to polymyxin B before and after polymyxin B exposure (A027(ind) and A009(ind)). The pmrAB and lpxACD were sequenced and their transcriptional levels were analyzed by qRT-PCR. The bacterial cell morphology was evaluated by transmission electronic microscopy (TEM) and the membrane potential was measured using Zeta-potential analyzer. The virulence of strains was studied using a Caenorhabditis elegans model. Both clinical isolates exhibited an elevation of the polymyxin B MIC after exposure to this compound. On the other hand, A027(ind) showed decreased values of MIC for β-lactams, aminoglycosides, vancomycin, teicoplanin, oxacillin and erythromycin. A027(ind) harbored two mutations in pmrB and the ISAba125 disrupting the lpxA. In contrast, A009(ind) strain exhibited increase of pmrB transcriptional level, after polymyxin B exposure, despite the absence of mutations in the pmrAB genes. The TEM images revealed a thicker and more electron-dense peptidoglycan layer for A009 than that of A027. The exposure to polymyxin B induced a strong condensation and darkening of intracellular material, mainly in A009(ind). In addition, the surface charge of A009 was significantly less negative than the one of A027. Using the C. elegans model, only A027(ind) strain showed a reduction on virulence. The diversity of polymyxin B resistance mechanisms among A. baumannii strains evaluated in this study confirms the complexity of these mechanisms, which may vary depending of the background of each strain.
通过比较云南烟蚜敏感品系和抗性品系的解毒酶(α-乙酸萘酯羧酸酯酶、β-乙酸萘酯羧酸酯酶)和靶标酶(乙酰胆碱酯酶)的活力,研究了烟蚜对有机磷、拟除虫菊酯和氨基甲酸酯类杀虫剂抗性的生化机制,并通过酯酶基因扩增检测和钠离子通道突变检测,研究了其抗性的分子机制.结果表明:α-乙酸萘酯羧酸酯酶活力增强是烟蚜对有机磷类、氨基甲酸酯类杀虫剂及拟除虫菊酯类杀虫剂的抗性机制之一；乙酰胆碱酯酶在烟蚜对有机磷杀虫剂抗性中起重要作用；3个抗性品系烟蚜均没有发生酯酶基因扩增,抗拟除虫菊酯品系烟蚜发生了钠离子通道突变.%To study the biochemical and molecular mechanism of resistance to organophosphorus, pyre- throid and carbarmate pesticide, the activity of the detoxicating enzymes (α - NA carboxylesterase, β — NA carboxylesterase) and the target enzyme ( acetylcholinesterase) were compared among the susceptible and the resistant strain of Myzus persicae. The results showed that enhanced α - NA carboxylesterase played an important role in the resistance to the three kinds of pesticides, so did the acetylcholinesterase to organophosphorus pesticide. All the three resistant strains had no amplified esterase genes, and the strain resistant to pyrethroid had a mutation in sodium channel.
Bressan, R.A.; Wilson, L.G.; Filner, P.
The relative resistance of four cultivars of the Cucurbitaceae (Cucumis sativus L. cv. National Pickling, and inbred line SC 25; Cucurbita pepo L. cv. Prolific Straightneck Squash, and cv. Small Sugar Pumpkin) to SO/sub 2/ was determined. According to plots of the degree of exposure to SO/sub 2/ (which depends on the SO/sub 2/ concentration and the duration of the exposure), there is an 8-fold difference in resistance to this toxic gas among these cultivars. However, if the degree of injury is plotted as a function of the amount of SO/sub 2/ absorbed, all four cultivars appear similarly sensitive to the gas. We conclude that the principal reason for special and varietal differences in resistance among these cultivars is the relative rate of absorption of the gas. The densities of stomata on the upper and lower surfaces of leaves did not differ sufficiently between cultivars to account for the differences in absorption rates. It remains to be determined whether the differences in rate of SO/sub 2/ absorption reflect differences in stomatal activity. Resistance of individual leaves changes with position on the plant axis (age of the leaf). There exists a gradient of decreasing resistance from the apex downward. This resistance gradient cannot be accounted for by differences in rates of SO/sub 2/ absorption. We infer the existence of a biochemically based, developmentally controlled resistance mechanism which functions after SO/sub 2/ has entered the leaf. Biochemical comparisons of old and young leaves with such differences in resistance should be helpful in determining the biochemistry of SO/sub 2/ toxicity.
Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V; Rizk, Shahir S; Njimoh, Dieudonne L; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M; Wiest, Olaf; Haldar, Kasturi
Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of resistance to them raises risk of wiping out recent gains achieved in reducing worldwide malaria burden and threatens future malaria control and elimination on a global level. Genome-wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination.
Dieras, Véronique; Vincent-Salomon, Anne; Degeorges, Armelle; Beuzeboc, Philippe; Mignot, Laurent; de Cremoux, Patricia
The detection of overexpression of human epidermal growth factor receptor 2 (HER2) in some breast cancer tumors has led to the development of a targeted treatment that is tumor selective, effective at extending life expectancy in the patients with advanced or early breast cancers. Trastuzumab (Herceptin), a humanized monoclonal antibody to HER2 is indicated for patients whose tumor demonstrates an amplified copy number for the HER2 oncogene and/or overexpresses the HER2 oncoprotein. Despite a high level of efficacy in combination with chemotherapy, trastuzumab as single agent has limited effectiveness (up to 30% response rates) and patients who respond to trastuzumab will relapse despite continued treatment. The mechanism of trastuzumab action is not fully understood but has been related to cell cycle inhibition. As to mechanisms of resistance, little is known but many preclinical data raised different hypothesis. Thus, the co-expression of growth factor receptors (EGFR family, IGF-1 R), and the activation of PI3K-Akt pathway, mainly by loss of PTEN function may be responsible for the resistance phenotype. It would be interesting to identify the mechanisms of trastuzumab resistance in breast tumors in order to reverse or prevent it. The characterization of these mechanisms would also provide novel strategies for alternative treatments.
Hong, S.; Chang, S. H.; Phatak, C.; Magyari-Kope, Blanka; Nishi, Y; Chattopadhyay, Soma; Kim, Jung Ho
Here we present our findings related to the mechanism of reversible resistivity in Pt/TiO2/Pt cells and in Ta2O5 thin films. Our findings for Pt/TiO2/Pt cells indicate that there exists a photovoltaic-like effect, which modulates the resistance reversibly by a few orders of magnitude, depending on the intensity of impinging x-rays. We found that this effect, combined with the x-ray irradiation induced phase transition confirmed by transmission electron microscopy, triggers a non-volatile reversible resistance change. For Ta2O5 thin films, we found that there are strong correlations among oxygen vacancy number and positions and energy gaps. Ab initio band structure calculations explain the evolution of the electronic excitation spectrum as a function of oxygen vacancy number and positions and importantly provide a predictive description of the oxygen deficient Ta oxide that may improve the desired performance based on atomic level design.
Frey, K.; Lombardo, M; Wright, D; Anderson, A
Resistance to therapeutics such as trimethoprim-sulfamethoxazole has become an increasing problem in strains of methicillin-resistant Staphylococcus aureus (MRSA). Clinically isolated trimethoprim-resistant strains reveal a double mutation, H30N/F98Y, in dihydrofolate reductase (DHFR). In order to develop novel and effective therapeutics against these resistant strains, we evaluated a series of propargyl-linked antifolate lead compounds for inhibition of the mutant enzyme. For the propargyl-linked antifolates, the F98Y mutation generates minimal (between 1.2- and 6-fold) losses of affinity and the H30N mutation generates greater losses (between 2.4- and 48-fold). Conversely, trimethoprim affinity is largely diminished by the F98Y mutation (36-fold) and is not affected by the H30N mutation. In order to elucidate a mechanism of resistance, we determined a crystal structure of a complex of this double mutant with a lead propargyl-linked antifolate. This structure suggests a resistance mechanism consistent both for the propargyl-linked class of antifolates and for trimethoprim that is based on the loss of a conserved water-mediated hydrogen bond.
Rice, Louis B.
The widespread use of antibiotics has resulted in a growing problem of antimicrobial resistance in the community and hospital settings. Antimicrobial classes for which resistance has become a major problem include the β-lactams, the glycopeptides, and the fluoroquinolones. In gram-positive bacteria, β-lactam resistance most commonly results from expression of intrinsic low-affinity penicillin-binding proteins. In gram-negative bacteria, expression of acquired β-lactamases presents a particular challenge owing to some natural spectra that include virtually all β-lactam classes. Glycopeptide resistance has been largely restricted to nosocomial Enterococcus faecium strains, the spread of which is promoted by ineffective infection control mechanisms for fecal organisms and the widespread use of colonization-promoting antimicrobials (especially cephalosporins and antianaerobic antibiotics). Fluoroquinolone resistance in community-associated strains of Escherichia coli, many of which also express β-lactamases that confer cephalosporin resistance, is increasingly prevalent. Economic and regulatory forces have served to discourage large pharmaceutical companies from developing new antibiotics, suggesting that the antibiotics currently on the market may be all that will be available for the coming decade. As such, it is critical that we devise, test, and implement antimicrobial stewardship strategies that are effective at constraining and, ideally, reducing resistance in human pathogenic bacteria. PMID:22305032
Weston, D.P., E-mail: firstname.lastname@example.org [Department of Integrative Biology, University of California, 3060 Valley Life Sciences Bldg., Berkeley, CA 94720-3140 (United States); Asbell, A.M., E-mail: email@example.com [Department of Integrative Biology, University of California, 3060 Valley Life Sciences Bldg., Berkeley, CA 94720-3140 (United States); Hecht, S.A., E-mail: firstname.lastname@example.org [NOAA Fisheries, Office of Protected Resources, 510 Desmond Drive S.E., Lacey, WA 98503 (United States); Scholz, N.L., E-mail: email@example.com [NOAA Fisheries, Northwest Fisheries Science Center, 2725 Montlake Blvd. E., Seattle, WA 98112 (United States); Lydy, M.J., E-mail: firstname.lastname@example.org [Fisheries and Illinois Aquaculture Center and Department of Zoology, Southern Illinois University, 171 Life Sciences II, Carbondale, IL 62901 (United States)
Urban streams of the Pacific Northwest provide spawning and rearing habitat for a variety of salmon species, and food availability for developing salmon could be adversely affected by pesticide residues in these waterbodies. Sediments from Oregon and Washington streams were sampled to determine if current-use pyrethroid insecticides from residential neighborhoods were reaching aquatic habitats, and if they were at concentrations acutely toxic to sensitive invertebrates. Approximately one-third of the 35 sediment samples contained measurable pyrethroids. Bifenthrin was the pyrethroid of greatest concern with regards to aquatic life toxicity, consistent with prior studies elsewhere. Toxicity to Hyalella azteca and/or Chironomus dilutus was found in two sediment samples at standard testing temperature (23 deg. C), and in one additional sample at a more environmentally realistic temperature (13 deg. C). Given the temperature dependency of pyrethroid toxicity, low temperatures typical of northwest streams can increase the potential for toxicity above that indicated by standard testing protocols. - Highlights: > Salmon-bearing creeks can be adversely impacted by insecticides from urban runoff. > Pyrethroid insecticides were found in one-third of the creeks in Washington and Oregon. > Two creeks contained concentrations acutely lethal to sensitive invertebrates. > Bifenthrin was of greatest concern, though less than in prior studies. > Standard toxicity testing underestimates the ecological risk of pyrethroids. - Pyrethroid insecticides are present in sediments of urban creeks of Oregon and Washington, though less commonly than in studies elsewhere in the U.S.
Teresa Maria Santos Amaral
Full Text Available Patients with castration-resistant prostate cancer (CRPC, who progress after docetaxel therapy, had until very recently, only a few therapeutic options. Recent advances in this field brought about new perspectives in the treatment of this disease. Molecular, basic, and translational research has given us a better understanding on the mechanisms of CRPC. This great investment has turned into a more rational approach to the development of new drugs. Some of the new treatments are already available to our patients outside clinical trials and may include inhibitors of androgen biosynthesis; new chemotherapy agents; bone-targeted therapy; and immunotherapy. This paper aims to review the mechanisms of prostate cancer resistance, possible therapeutic targets, as well as new options to treat CRPC.
Full Text Available In recent years, structural and functional studies reveal that tyrosine kinases (TKs act as the essential components of signal transduction pathways that regulate cancer cell proliferation, apoptosis and angiogenesis, and therefore become potential targets for anticancer therapy. Most of TK inhibitors (TKIs are small molecular and hydrophobic compounds, thus they can rapidly reach their specific intracellular targets and inhibit the activation of the related TKs. Unfortunately, accompanied with patients who gain great benefit of TKIs therapy, increasing evidences of acquired resistance to these agents have been documented. The unveiling point mutations within the kinase domain, gene amplification or overexpression, or modification of signaling pathway have been implicated in drug resistance. Additionally, overexpression of ABC transporters is likely to set stage for resistant development. In this review, we focus on the discussion of the molecular mechanisms of acquired resistance to TKIs therapy. The mechanistic understanding may help to put forward new hypotheses on drug development and design better therapies to overcome TKIs resistance.
Bodoev, I N; Il'ina, E N
Neisseria gonorrhoeae (gonococcus) is a strict human pathogen, which causes gonorrhea--an infectious disease, whose origin dates back to more than two thousand years. Due to the unique plasticity of the genetic material, these bacteria have acquired the capacity to adapt to the host immune system, cause repeated infections, as well as withstand antimicrobials. Since the introduction of antibiotics in 1930s, gonococcus has displayed its propensity to develop resistance to all clinically useful antibiotics. It is important to note that the known resistance determinants of N. gonorrhoeae were acquired through horizontal gene transfer, recombination and spontaneous mutagenesis, and may be located both in the chromosome and on the plasmid. After introduction of a new antimicrobial drug, gonococcus becomes resistant within two decades and replaces sensitive bacterial population. Currently Ceftriaxone is the last remaining antibiotic for first-line treatment of gonorrhea. However, the first gonococcus displaying high-level resistance to Ceftriaxone was isolated in Japan a few years ago. Therefore, in the near future, gonorrhea may become untreatable. In the present review, we discuss the chronology of the anti-gonorrhea drugs (antibiotics) replacement, the evolution of resistance mechanisms emergence and future perspectives of N. gonorrhoeae treatment.
Kruser, Tim J. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Wheeler, Deric L., E-mail: email@example.com [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI (United States)
The epidermal growth factor (EGF) family of receptor tyrosine kinases consists of four members: EGFR (HER1/ErbB1), HER2/neu (ErbB2), HER3 (ErbB3) and HER4 (ErbB4). Receptor activation via ligand binding leads to downstream signaling that influence cell proliferation, angiogenesis, invasion and metastasis. Aberrant expression or activity of EGFR and HER2 have been strongly linked to the etiology of several human epithelial cancers including but not limited to head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and breast cancer. With this, intense efforts have been made to inhibit the activity of the EGFR and HER2 by designing antibodies against the ligand binding domains (cetuximab, panitumumab and trastuzumab) or small molecules against the tyrosine kinase domains (erlotinib, gefitinib, and lapatinib). Both approaches have shown considerable clinical promise. However, increasing evidence suggests that the majority of patients do not respond to these therapies, and those who show initial response ultimately become refractory to treatment. While mechanisms of resistance to tyrosine kinase inhibitors have been extensively studied, resistance to monoclonal antibodies is less well understood, both in the laboratory and in the clinical setting. In this review, we discuss resistance to antibody-based therapies against the EGFR and HER2, similarities between these resistance profiles, and strategies to overcome resistance to HER family targeting monoclonal antibody therapy.
Chen, Liangbi; Chen, Wenfeng; Ma, Chunhua; Du, Dan; Chen, Xi
A novel solid-phase microextraction (SPME) fiber coated with multiwalled carbon nanotubes/polypyrrole (MWCNTs/Ppy) was prepared with an electrochemical method and used for the extraction of pyrethroids in natural water samples. The results showed that the MWCNTs/Ppy coated fiber had high organic stability, and remarkable acid and alkali resistance. In addition, the MWCNTs/Ppy coated fiber was more effective and superior to commercial PDMS and PDMS/DVD fibers in extracting pyrethroids in natural water samples. Under optimized conditions, the calibration curves were found to be linear from 0.001 to 10 μg mL(-1) for five of the six pyrethroids studied, the exception being fenvalerate (which was from 0.005 to 10 μg mL(-1)), and detection limits were within the range 0.12-0.43 ng mL(-1). The recoveries of the pyrethroids spiked in water samples at 10 ng mL(-1) ranged from 83 to 112%.
Choudhary, Devendra K; Prakash, Anil; Johri, B N
Plants possess a range of active defense apparatuses that can be actively expressed in response to biotic stresses (pathogens and parasites) of various scales (ranging from microscopic viruses to phytophagous insect). The timing of this defense response is critical and reflects on the difference between coping and succumbing to such biotic challenge of necrotizing pathogens/parasites. If defense mechanisms are triggered by a stimulus prior to infection by a plant pathogen, disease can be reduced. Induced resistance is a state of enhanced defensive capacity developed by a plant when appropriately stimulated. Systemic acquired resistance (SAR) and induced systemic resistance (ISR) are two forms of induced resistance wherein plant defenses are preconditioned by prior infection or treatment that results in resistance against subsequent challenge by a pathogen or parasite. Selected strains of plant growth-promoting rhizobacteria (PGPR) suppress diseases by antagonism between the bacteria and soil-borne pathogens as well as by inducing a systemic resistance in plant against both root and foliar pathogens. Rhizobacteria mediated ISR resembles that of pathogen induced SAR in that both types of induced resistance render uninfected plant parts more resistant towards a broad spectrum of plant pathogens. Several rhizobacteria trigger the salicylic acid (SA)-dependent SAR pathway by producing SA at the root surface whereas other rhizobacteria trigger different signaling pathway independent of SA. The existence of SA-independent ISR pathway has been studied in Arabidopsis thaliana, which is dependent on jasmonic acid (JA) and ethylene signaling. Specific Pseudomonas strains induce systemic resistance in viz., carnation, cucumber, radish, tobacco, and Arabidopsis, as evidenced by an enhanced defensive capacity upon challenge inoculation. Combination of ISR and SAR can increase protection against pathogens that are resisted through both pathways besides extended protection to a
. Conclusion This first investigation of malaria vector susceptibility to insecticides in Chad revealed variable levels of resistance to pyrethroid insecticides (permethrin and deltamethrin in most An. gambiae s.l. populations. Resistance was associated with the L1014F kdr mutation in the S form of An. gambiae s.s.. Alternative mechanisms, probably of metabolic origin are involved in An. arabiensis. These results emphasize the crucial need for insecticide resistance monitoring and in-depth investigation of resistance mechanisms in malaria vectors in Chad. The impact of reduced susceptibility to pyrethroids on ITN efficacy should be further assessed.
Full Text Available Abstract Background Fluoroquinolone resistant E. coli isolates, that are also resistant to other classes of antibiotics, is a significant challenge to antibiotic treatment and infection control policies. In Central Greece a significant increase of ciprofloxacin-resistant Escherichia coli has occurred during 2011, indicating the need for further analysis. Methods A total of 106 ciprofloxacin-resistant out of 505 E. coli isolates consecutively collected during an eight months period in a tertiary Greek hospital of Central Greece were studied. Antimicrobial susceptibility patterns and mechanisms of resistance to quinolones were assessed, whereas selected isolates were further characterized by multilocus sequence typing and β-lactamase content. Results Sequence analysis of the quinolone-resistance determining region of the gyrA and parC genes has revealed that 63% of the ciprofloxacin-resistant E. coli harbored a distinct amino acid substitution pattern (GyrA:S83L + D87N; ParC:S80I + E84V, while 34% and 3% carried the patterns GyrA:S83L + D87N; ParC:S80I and GyrA:S83L + D87N; ParC:S80I + E84G respectively. The aac (6’-1b-cr plasmid-mediated quinolone resistance determinant was also detected; none of the isolates was found to carry the qnrA, qnrB and qnrS. Genotyping of a subset of 35 selected ciprofloxacin-resistant E. coli by multilocus sequence typing has revealed the presence of nine sequence types; ST131 and ST410 were the most prevalent and were exclusively correlated with hospital and health care associated infections, while strains belonging to STs 393, 361 and 162 were associated with community acquired infections. The GyrA:S83L + D87N; ParC:S80I + E84V substitution pattern was found exclusively among ST131 ciprofloxacin-resistant E. coli. Extended-spectrum β-lactamase-positive ST131 ciprofloxacin-resistant isolates produced CTX-M-type enzymes; eight the CTX-M-15 and one the CTX-M-3 variant. CTX-M-1 like and KPC-2 enzymes were detected
Full Text Available Breast cancer represents one of the most common cancers in women and is a major life threatening illness found all over the world. Therapy approaches include irradiation and surgery, with chemotherapy considered an important strategy to treat breast cancer. Platinum based anticancer drugs, such as cisplatin (cis-di-amino-dichloride-platin, CDDP, carboplatin, orthoplatin, etc., have been successfully used in breast cancer therapy because they activate multiple mechanisms to induce apoptosis in tumor cells. Nevertheless, during chemotherapy, drug resistance frequently develops; this impairs the successful treatment of breast cancer and often leads to patients’ decease. While combinations of anticancer drugs used in chemotherapy regimens reduced the occurrence of drug resistance (e.g. doxorubicin + docetaxel, doxorubicin + cyclophosphamide, docetaxel + herceptin + carboplatin the molecular mechanism of those effects are not completely understood. Here we review possible mechanisms related to breast cancer treatment and resistance to current therapies as well as possible new therapeutic targets (e.g. calcium signaling which could be used in the future.
DUAN Can-xing; ZHANG Shi-xian; LEI Cai-lin; CHENG Zhi-jun; CHEN Qing; ZHAI Hu-qu; WAN Jian-min
One hundred and thirty-eight rice accessions were screened for resistance to the small brown planthopper(SBPH)resistance to SBPH were detected,accounting for 18.1%of the total accessions,which included 2 highly resistant,9 resistant and 14 moderately resistant varieties.Compared with indica rice,japonica rice was more susceptible to SBPH.Antixenosis test,antibiosis test and correlation analysis were performed to elucidate the resistance mechanism.The resistant check Rathu Heenati(RHT),highly resistant varieties Mudgo and Kasalath,and resistant variety IR36 expressed strong antixenosis and antibiosis against SBPH,indicating the close relationship between resistance level and these two resistance mechanisms in the four rice varieties.Antibiosis was the dominant resistance pattern in the resistant varieties Daorenqiao and Yangmaogu due to their high antibiosis but low antixenosis.Dular,ASD7 and Milyang 23 had relatively strong antixenosis and antibiosis,indicating the two resistance mechanisms were significant in these three varieties.The resistant DV85 expressed relatively high level of antixenosis but low antibiosis,whereas Zhaiyeqing 8 and Guiyigu conferred only moderate antibiosis and antixenosis to SBPH,suggesting tolerance in these three varieties.Antibiosis and antixenosis governed the resistance to SBPH in the moderately resistant accession 9311.Antixenosis was the main resistance type in V20A.Tolerance was considered to be an important resistance mechanism in Minghui 63 and Yangjing 9538 due to their poor antibiosis and antixenosis resistance.The above accessions with strong antibiosis or antixenosis were the ideal materials for the resistance breeding.
Yang, Jian-Zeng; Ma, Shu-Rong; Rong, Xiao-Li; Zhu, Mei-Ju; Ji, Qiu-Ye; Meng, Ling-Jie; Gao, Yi-Yao; Yang, Yu-Dan; Wang, Yan
Multidrug resistance (MDR) is a challenge for the treatment of cancer and the underlying molecular mechanisms remain elusive. The current study exposed MG63 osteosarcoma cells to increasing concentrations of vincristine (VCR) to establish four VCR‑resistant MG63/VCR cell sublines (MG63/VCR1, 2, 3 and 4). The drug resistance indices (RI) of these sublines was detected with the CCK‑8 assay and determined to be163, 476, 1,247, and 2,707‑fold higher than that of parental cells, respectively. These sublines also exhibited cross‑resistance to doxorubicin, paclitaxel and pirarubicin. With increased RI, the proliferative capacity of these sublines was gradually reduced and cell morphology was also altered, characterized by increased formation of pseudopodia and long cytoplasmic processes at opposite poles. However, the migration capacity and expression of certain drug resistance‑associated genes were not in accordance with the increased RI; multidrug resistance protein 1 (MDR1) expression was significantly increased in these sublines compared with parental cells. However, in the highly resistant MG63/VCR3 and MG63/VCR4 cells, MDR‑associated protein 1, topoisomerase II and LIM domain kinase 1 levels were significantly reduced compared with the moderately resistant MG63/VCR2 cells. Expression of glutathione S‑transferase‑π mRNA was determined using reverse transcription‑quantitative polymerase chain reaction and determined that it was not changed between MG63 and MG63/VCR cells. The data of the present study demonstrated that the molecular alterations of drug resistance may change with the degree of drug resistance. Taking cell morphology into consideration, the intratumor clonal and phenotypic heterogeneity may be responsible for drug resistance. These MG63/VCR sublines may be a valuable tool to assess drug resistance and the underlying mechanisms, and to identify novel drug resistance‑associated genes or strategies to overcome MDR in human
Davidson, Lance A
Morphogenesis requires the spatial and temporal control of embryo mechanics, including force production and mechanical resistance to those forces, to coordinate tissue deformation and large-scale movements. Thus, biomechanical processes play a key role in directly shaping the embryo. Additional roles for embryo mechanics during development may include the patterning of positional information and to provide feedback to ensure the success of morphogenetic movements in shaping the larval body and organs. To understand the multiple roles of mechanics during development requires familiarity with engineering principles of the mechanics of structures, the viscoelastic properties of biomaterials, and the integration of force and stress within embryonic structures as morphogenesis progresses. In this chapter, we review the basic engineering principles of biomechanics as they relate to morphogenesis, introduce methods for quantifying embryo mechanics and the limitations of these methods, and outline a formalism for investigating the role of embryo mechanics in birth defects. We encourage the nascent field of embryo mechanics to adopt standard engineering terms and test methods so that studies of diverse organisms can be compared and universal biomechanical principles can be revealed.
Yook-Kong; YONG; Mihir; S; PATEL
A novel design method for high Q piezoelectric resonators was presented and proposed using the 3-D equations of linear piezoelectricity with quasi-electrostatic approximation which include losses attributed to mechanical damping in solid and resistance in current conduction. There is currently no finite element software for estimating the Q of a resonator without apriori assumptions of the resonator impedance or damping. There is a necessity for better and more realistic modeling of resonators and filters due to miniaturization and the rapid advances in frequency ranges in telecommunication.We presented new three-dimensional finite element models of quartz and barium titanate resonators with mechanical damping and resistance in current conduction. Lee, Liu and Ballato's 3-D equations of linear piezoelectricity with quasi-electro- static approximation which include losses attributed to mechanical damping in solid and resistance in current conduction were formulated in a weak form and implemented in COMSOL. The resulting finite element model could predict the Q and other electrical parameters for any piezoelectric resonator without apriori assumptions of damping or resistance. Forced and free vibration analyses were performed and the results for the Q and other electrical parameters were obtained. Comparisons of the Q and other electrical parameters obtained from the free vibration analysis with their corresponding values from the forced vibration analysis were found to be in excellent agreement. Hence, the frequency spectra obtained from the free vibration analysis could be used for designing high Q resonators. Results for quartz thickness shear AT-cut and SC-cut resonators and thickness stretch poled barium titanate resonators were presented. An unexpected benefit of the model was the prediction of resonator Q with energy losses via the mounting supports.
Full Text Available Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1, and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.
Li, Xianchun; Schuler, Mary A; Berenbaum, May R
Xenobiotic resistance in insects has evolved predominantly by increasing the metabolic capability of detoxificative systems and/or reducing xenobiotic target site sensitivity. In contrast to the limited range of nucleotide changes that lead to target site insensitivity, many molecular mechanisms lead to enhancements in xenobiotic metabolism. The genomic changes that lead to amplification, overexpression, and coding sequence variation in the three major groups of genes encoding metabolic enzymes, i.e., cytochrome P450 monooxygenases (P450s), esterases, and glutathione-S-transferases (GSTs), are the focus of this review. A substantial number of the adaptive genomic changes associated with insecticide resistance that have been characterized to date are transposon mediated. Several lines of evidence suggest that P450 genes involved in insecticide resistance, and perhaps insecticide detoxification genes in general, may share an evolutionary association with genes involved in allelochemical metabolism. Differences in the selective regime imposed by allelochemicals and insecticides may account for the relative importance of regulatory or structural mutations in conferring resistance.
Brand, Toni M; Iida, Mari; Wheeler, Deric L
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase belonging to the HER family of receptor tyrosine kinases. Receptor activation upon ligand binding leads to down stream activation of the PI3K/AKT, RAS/RAF/MEK/ERK and PLCγ/PKC pathways that influence cell proliferation, survival and the metastatic potential of tumor cells. Increased activation by gene amplification, protein overexpression or mutations of the EGFR has been identified as an etiological factor in a number of human epithelial cancers (e.g., NSCLC, CRC, glioblastoma and breast cancer). Therefore, targeting the EGFR has been intensely pursued as a cancer treatment strategy over the last two decades. To date, five EGFR inhibitors, including three small molecule tyrosine kinase inhibitors (TKIs) and two monoclonal antibodies have gained FDA approval for use in oncology. Both approaches to targeting the EGFR have shown clinical promise and the anti-EGFR antibody cetuximab is used to treat HNSCC and CRC. Despite clinical gains arising from use of cetuximab, both intrinsic resistance and the development of acquired resistance are now well recognized. In this review we focus on the biology of the EGFR, the role of EGFR in human cancer, the development of antibody-based anti-EGFR therapies and a summary of their clinical successes. Further, we provide an in depth discussion of described molecular mechanisms of resistance to cetuximab and potential strategies to circumvent this resistance.
Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.
El-Tanani, Mohamed; Dakir, El-Habib; Raynor, Bethany; Morgan, Richard
Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES) to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1), and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.
Leptin signaling blockade by chronic overstimulation of the leptin receptor or hypothalamic pro-inflammatory responses due to elevated levels of saturated fatty acid can induce leptin resistance by activating negative feedback pathways. Although, long form leptin receptor (Ob-Rb) initiates leptin signaling through more than seven different signal transduction pathways, excessive suppressor of cytokine signaling-3 (SOCS-3) activity is a potential mechanism for the leptin resistance that characterizes human obesity. Because the leptin-responsive metabolic pathways broadly integrate with other neurons to control energy balance, the methods used to counteract the leptin resistance has extremely limited effect. In this chapter, besides the impairment of central and peripheral leptin signaling pathways, limited access of leptin to central nervous system (CNS) through blood-brain barrier, mismatch between high leptin and the amount of leptin receptor expression, contradictory effects of cellular and circulating molecules on leptin signaling, the connection between leptin signaling and endoplasmic reticulum (ER) stress and self-regulation of leptin signaling has been discussed in terms of leptin resistance.
Resistance to chloroquine of malaria strains is known to be associated with a parasite protein named PfCRT, the mutated form of which is able to reduce chloroquine accumulation in the digestive vacuole of the pathogen. Whether the protein mediates extrusion of the drug acting as a channel or as a carrier and which is the protonation state of its chloroquine substrate is the subject of a scientific debate. We present here an analytical approach that explores which combination of hypotheses on the mechanism of transport and the protonation state of chloroquine are consistent with available equilibrium experimental data. We show that the available experimental data are not, by themselves, sufficient to conclude whether the protein acts as a channel or as a transporter, which explains the origin of their different interpretation by different authors. Interestingly, though, each of the two models is only consistent with a subset of hypotheses on the protonation state of the transported molecule. The combination of these results with a sequence and structure analysis of PfCRT, which strongly suggests that the molecule is a carrier, indicates that the transported species is either or both the mono and di-protonated forms of chloroquine. We believe that our results, besides shedding light on the mechanism of chloroquine resistance in P. falciparum, have implications for the development of novel therapies against resistant malaria strains and demonstrate the usefulness of an approach combining systems biology strategies with structural bioinformatics and experimental data.
Maria Niures P.S. Matioli
Full Text Available Several studies have indicated that Diabetes Mellitus (DM can increase the risk of developing Alzheimer's disease (AD. This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection.
Marjorie Rose Levinstein
Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.
Edern, Anita; Fines-Guyon, Marguerite; Castrale, Cindy; Ficheux, Maxence; Ryckelynck, Jean-Philippe; Lobbedez, Thierry
Peritonitis remains a common complication of peritoneal dialysis. The aim of our study is to describe the mechanisms of antibiotic resistance in bacteria isolated during peritonitis in peritoneal dialysis, to determine whether antibiotic therapy proposed by the International Society for Peritoneal Dialysis (ISPD) is adapted to the mechanisms of resistance. All causative microorganisms of peritonitis, isolated in 106 dialysis patients and reported 170 episodes of peritonitis, during the study period (01/01/2005 to 31/12/2010) were reviewed. According to the usual classification, twelve groups of microorganism were created. An interpretive reading of antibiograms was performed in each group to identify resistance phenotypes. The species most frequently isolated are coagulase-negative staphylococci (n=73) of which 46 had PBP2a (penicillin-binding protein). Many Enterobacteriaceae were also isolated (n=45), they are susceptible to third generation cephalosporins with the exception of Enterobacteriaceae producing an extended spectrum β-lactamase (ESBL) or a cephalosporinase. Except for staphylococci, probabilistic antibiotic therapy recommended by the ISPD to treat peritonitis is effective. Indeed, many staphylococci producing a PBP2a, a first-generation cephalosporin cannot be administered in all cases. It is therefore necessary to identify patients with a strain of staphylococcus producing a PBP2a, it must be treated by vancomycin.
Lyngs Jørgensen, H J; Lübeck, P S; Thordal-Christensen, H; de Neergaard, E; Smedegaard-Petersen, V
ABSTRACT Quantitative and qualitative histopathological methods and molecular analyses were used to study the mechanisms by which preinoculation with either of the nonbarley pathogens, Bipolaris maydis and Septoria nodorum, inhibited growth of Drechslera teres. Collectively, our data suggest that induced resistance is the principal mechanism responsible for impeding the pathogen. The enhancement of resistance in the host was primarily manifested during penetration by D. teres, and after penetration, where growth of D. teres ceased soon after development of infection vesicles. Thus, 24 h after pretreatment with B. maydis or S. nodorum, the penetration frequency from D. teres appressoria was reduced from 42.7% in the controls to 9.5 and 14.8%, respectively. The reductions were associated with increased formation of fluorescent papillae in induced cells (early defense reaction). The postpenetrational inhibition of D. teres completely stopped fungal growth and was apparently linked to an enhancement of multicellular hypersensitive responses in inducer-treated leaves (late defense reaction). Papillae formation and multicellular hypersensitive reactions were also observed in fully susceptible, noninduced control leaves, but they were inadequate to stop fungal progress. Northern blots from leaves treated with either inducer alone support the conclusion that induced resistance is involved in suppression of D. teres by increased formation of papillae and hypersensitive reactions. Thus, the blots showed strong expression of several defense response genes that are involved in these reactions in barley attacked by Erysiphe graminis f. sp. hordei.
ZHOU Xingang; WU Fengzhi; WANG Xuezheng; YUAN Ye
Fusarium wilt caused by Fusarium oxysporum f.sp.cucumerinum (Owen) is one of the most devastating diseases in cucumber production worldwide.Recent progresses in the mechanism of resistance to Fusarium wilt in cucumber were reviewed in this paper,including pathogenic mechanism of Fusarium oxysporum,the resistance mechanism of cucumber,the heredity of resistance,and the location of resistance genes.Following works should be the location and cloning of resistance genes with molecular biologic methods.
Ishrat J Azmi
Full Text Available To investigate the prevalence and mechanisms of fluoroquinolone resistance in Shigella species isolated in Bangladesh and to compare with similar strains isolated in China.A total of 3789 Shigella isolates collected from Clinical Microbiology Laboratory of icddr,b, during 2004-2010 were analyzed for antibiotic susceptibility. Analysis of plasmids, plasmid-mediated quinolone-resistance genes, PFGE, and sequencing of genes of the quinolone-resistance-determining regions (QRDR were conducted in representative strains isolated in Bangladesh and compared with strains isolated in Zhengding, China. In addition, the role of efflux-pump was studied by using the efflux-pump inhibitor carbonyl cyanide-m-chlorophenylhydrazone (CCCP.Resistance to ciprofloxacin in Shigella species increased from 0% in 2004 to 44% in 2010 and S. flexneri was the predominant species. Of Shigella spp, ciprofloxacin resistant (CipR strains were mostly found among S. flexneri (8.3%, followed by S. sonnei (1.5%. Within S. flexneri (n = 2181, 14.5% were resistance to ciprofloxacin of which serotype 2a was predominant (96%. MIC of ciprofloxacin, norfloxacin, and ofloxacin were 6-32 mg/L, 8-32 mg/L, and 8-24 mg/L, respectively in S. flexneri 2a isolates. Sequencing of QRDR genes of resistant isolates showed double mutations in gyrA gene (Ser83Leu, Asp87Asn/Gly and single mutation in parC gene (Ser80Ile. A difference in amino acid substitution at position 87 was found between strains isolated in Bangladesh (Asp87Asn and China (Asp87Gly except for one. A novel mutation at position 211 (His→Tyr in gyrA gene was detected only in the Bangladeshi strains. Susceptibility to ciprofloxacin was increased by the presence of CCCP indicating the involvement of energy dependent active efflux pumps. A single PFGE type was found in isolates from Bangladesh and China suggesting their genetic relatedness.Emergence of fluoroquinolone resistance in Shigella undermines a major challenge in current
Azmi, Ishrat J.; Khajanchi, Bijay K.; Akter, Fatema; Hasan, Trisheeta N.; Shahnaij, Mohammad; Akter, Mahmuda; Banik, Atanu; Sultana, Halima; Hossain, Mohammad A.; Ahmed, Mohammad K.; Faruque, Shah M.; Talukder, Kaisar A.
Objective To investigate the prevalence and mechanisms of fluoroquinolone resistance in Shigella species isolated in Bangladesh and to compare with similar strains isolated in China. Methods A total of 3789 Shigella isolates collected from Clinical Microbiology Laboratory of icddr,b, during 2004–2010 were analyzed for antibiotic susceptibility. Analysis of plasmids, plasmid-mediated quinolone-resistance genes, PFGE, and sequencing of genes of the quinolone-resistance-determining regions (QRDR) were conducted in representative strains isolated in Bangladesh and compared with strains isolated in Zhengding, China. In addition, the role of efflux-pump was studied by using the efflux-pump inhibitor carbonyl cyanide-m-chlorophenylhydrazone (CCCP). Results Resistance to ciprofloxacin in Shigella species increased from 0% in 2004 to 44% in 2010 and S. flexneri was the predominant species. Of Shigella spp, ciprofloxacin resistant (CipR) strains were mostly found among S. flexneri (8.3%), followed by S. sonnei (1.5%). Within S. flexneri (n = 2181), 14.5% were resistance to ciprofloxacin of which serotype 2a was predominant (96%). MIC of ciprofloxacin, norfloxacin, and ofloxacin were 6–32 mg/L, 8–32 mg/L, and 8–24 mg/L, respectively in S. flexneri 2a isolates. Sequencing of QRDR genes of resistant isolates showed double mutations in gyrA gene (Ser83Leu, Asp87Asn/Gly) and single mutation in parC gene (Ser80Ile). A difference in amino acid substitution at position 87 was found between strains isolated in Bangladesh (Asp87Asn) and China (Asp87Gly) except for one. A novel mutation at position 211 (His→Tyr) in gyrA gene was detected only in the Bangladeshi strains. Susceptibility to ciprofloxacin was increased by the presence of CCCP indicating the involvement of energy dependent active efflux pumps. A single PFGE type was found in isolates from Bangladesh and China suggesting their genetic relatedness. Conclusions Emergence of fluoroquinolone resistance in Shigella
Goodman, K E; Simner, P J; Tamma, P D; Milstone, A M
The Centers for Disease Control and Prevention (CDC) defines carbapenem-resistant Enterobacteriaceae (CRE) based upon a phenotypic demonstration of carbapenem resistance. However, considerable heterogeneity exists within this definitional umbrella. CRE may mechanistically differ by whether they do or do not produce carbapenemases. Moreover, patients can acquire CRE through multiple pathways: endogenously through antibiotic selective pressure on intestinal microbiota, exogenously through horizontal transmission or through a combination of these factors. Some evidence suggests that non-carbapenemase-producing CRE may be more frequently acquired by antibiotic exposure and carbapenemase-producing CRE via horizontal transmission, but definitive data are lacking. This review examines types of CRE resistance mechanisms, antibiotic exposure and horizontal transmission pathways of CRE acquisition, and the implications of these heterogeneities to the development of evidence-based CRE healthcare epidemiology policies. In our Expert Commentary & Five-Year View, we outline specific nosocomial CRE knowledge gaps and potential methodological approaches for their resolution.
Pyrethroids insecticides commonly used in pest control disrupt the normal function of voltage-sensitive sodium channels. We have previously demonstrated that permethrin (a Type I pyrethroid) and deltamethrin (a Type II pyrethroid) inhibit sodium channel-dependent spontaneous netw...
ccanccapa, alexander; Masia, Ana; Pico, Yolanda
Pyrethroids are the synthetic analogues of pyrethrins which were developed as pesticides from the extracts of dried and powdered flower heads of Chrysanthemum cinerariaefolium. They are increasingly used in agriculture due to their broad biological activity and slow development of pest resistance. Contamination of fresh-water ecosystems appears either because of the direct discharge of industrial and agricultural effluents or as a result of effluents from sewage treatment works; residues can thus accumulate in the surrounding biosphere [1, 2]. These substances, mostly determined by gas chromatography mass spectrometry (GC-MS) can be difficult to analyse due to their volatility and degradability. The purpose of this study is, as an alternative, to develop a fast and sensitive multi-residue method for the target analysis of 7 pyrethroids and the 6 natural pyrethrins currently used in water samples by liquid chromatography tandem mass spectrometry (LC-MS/MS). The compounds included in the study were acrinathrin, etofenprox, cyfluthrin, esfenvalerate, cyhalothrin, cypermethrin and flumethrin as pyrethroids and a commercial mix of pyrethrins containing Cinerin I, Jasmolin I, pyrethrin I, cinerin II, jasmolin II, pyrethrins II in different percentages. As a preliminary step, the ionization and fragmentation of the compounds were optimized injecting individual solutions of each analyte at 10 ppm in the system, using a gradient elution profile of water-methanol both with 10 mM ammonium formate. The ESI conditions were: capillary voltage 4000 V, nebulizer15 psi, source temperature 300◦C and gas flow 10 L min-1. [M+H]+, [M+Na]+ ,[M+NH3]+ ,[M+NH4+]+ were tested as precursor ions. The most intense signal was for ammonium adduct for all compounds. The optimal fragmentor range for product ions were between 20 to 80 ev and the collision energy ranged between 5 to 86 ev. The efficiency of the method was tested in water samples from Turia River without any known exposure to
Ahmad, Sahil; Gupta, Sudheer; Kumar, Rahul; Varshney, Grish C; Raghava, Gajendra P S
Monoclonal antibody Trastuzumab/Herceptin is considered as frontline therapy for Her2-positive breast cancer patients. However, it is not effective against several patients due to acquired or de novo resistance. In last one decade, several assays have been performed to understand the mechanism of Herceptin resistance with/without supplementary drugs. This manuscript describes a database HerceptinR, developed for understanding the mechanism of resistance at genetic level. HerceptinR maintains information about 2500 assays performed against various breast cancer cell lines (BCCs), for improving sensitivity of Herceptin with or without supplementary drugs. In order to understand Herceptin resistance at genetic level, we integrated genomic data of BCCs that include expression, mutations and copy number variations in different cell lines. HerceptinR will play a vital role in i) designing biomarkers to identify patients eligible for Herceptin treatment and ii) identification of appropriate supplementary drug for a particular patient. HerceptinR is available at http://crdd.osdd.net/raghava/herceptinr/.
Darvish, Armin; Goyal, Gaurav; Aneja, Rachna; Sundaram, Ramalingam V. K.; Lee, Kidan; Ahn, Chi Won; Kim, Ki-Bum; Vlahovska, Petia M.; Kim, Min Jun
Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various liposomes inside nanopores. We observed a significant difference in resistive pulse characteristics between soft liposomes and rigid polystyrene nanoparticles especially at higher applied voltages. We used theoretical simulations to demonstrate that the difference can be explained by shape deformation of liposomes as they translocate through the nanopores. Comparing our results with the findings from electrodeformation experiments, we demonstrated that the rigidity of liposomes can be qualitatively compared using resistive pulse characteristics. This application of nanopores can provide new opportunities to study the mechanics at the nanoscale, to investigate properties of great value in fundamental biophysics and cellular mechanobiology, such as virus deformability and fusogenicity, and in applied sciences for designing novel drug/gene delivery systems.Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various
Guo, Wei; Cui, Shenghui; Xu, Xiao; Wang, Haoyan
Benzalkonium chloride is one of the invaluable biocides that is extensively used in healthcare settings as well as in the food processing industry. After exposing wild-type Salmonella Typhimurium 14028s or its AcrAB inactivation mutant to gradually increasing levels of benzalkonium chloride, resistance mutants S-41, S-150, S-AB-23, S-AB-38, and S-AB-73 were selected and these mutants also showed a 2-64-fold stable minimum inhibitory concentration (MIC) increase to chloramphenicol, ciprofloxacin, nalidixic acid, and tetracycline. In S-41 and S-150, the expression of acrB was increased 2.7- and 7.6-fold, and ΔtolC or ΔacrAB mutants of S-41 and S-150 showed the same MICs to all tested antimicrobials as the equivalent Salmonella Typhimurium 14028s mutants. However, in S-AB-23, S-AB-38, and S-AB-73, the expression of acrF was increased 96-, 230-, and 267-fold, respectively, and ΔtolC or ΔacrEF mutants of S-AB-23, S-AB-38, and S-AB-73 showed the similar MICs to all tested antimicrobials as the ΔtolC mutant of Salmonella Typhimurium 14028s. Our data showed that constitutively over-expressed AcrAB working through TolC was the main resistance mechanism in ST14028s benzalkonium chloride resistance mutants. However, after AcrAB had been inactivated, benzalkonium chloride-resistant mutants could still be selected and constitutively over-expressed, AcrEF became the dominant efflux pump working through TolC and being responsible for the increasing antimicrobial resistance. These data indicated that different mechanisms existed for acrB and acrF constitutive over-expression. Since exposure to benzalkonium chloride may lead to Salmonella mutants with a decreased susceptibility to quinolones, which is currently one of the drugs of choice for the treatment of life-threatening salmonelosis, research into the pathogenesis and epidemiology of the benzalkonium chloride resistance mutants will be of increasing importance.
Rudolph, Karen; Bulkow, Lisa; Bruce, Michael; Zulz, Tammy; Reasonover, Alisa; Harker-Jones, Marcella; Hurlburt, Debby; Hennessy, Thomas
The rapid emergence of antibiotic-resistant pneumococcal strains has reduced treatment options. The aim of this study was to determine antimicrobial susceptibilities, serotype distributions, and molecular resistance mechanisms among macrolide-resistant invasive pneumococcal isolates in Alaska from 1986 to 2010. We identified cases of invasive pneumococcal disease in Alaska from 1986 to 2010 through statewide population-based laboratory surveillance. All invasive pneumococcal isolates submitted to the Arctic Investigations Program laboratory were confirmed by standard microbiological methods and serotyped by slide agglutination and the Quellung reaction. MICs were determined by the broth microdilution method, and macrolide-resistant genotypes were determined by multiplex PCR. Among 2,923 invasive pneumococcal isolates recovered from 1986 to 2010, 270 (9.2%) were nonsusceptible to erythromycin; 177 (66%) erythromycin-nonsusceptible isolates demonstrated coresistance to penicillin, and 167 (62%) were multidrug resistant. The most frequent serotypes among the macrolide-resistant isolates were serotypes 6B (23.3%), 14 (20.7%), 19A (16.7%), 9V (8.9%), 19F (6.3%), 6A (5.6%), and 23F (4.8%). mef and erm(B) genes were detected in 207 (77%) and 32 (12%) of the isolates, respectively. Nineteen (7%) of the erythromycin-nonsusceptible isolates contained both mef and erm(B) genotypes; 15 were of serotype 19A. There was significant year-to-year variation in the proportion of isolates that were nonsusceptible to erythromycin (P resistance among pneumococcal isolates from Alaska is mediated predominantly by mef genes, and this has not changed significantly over time. However, there was a statistically significant increase in the proportion of isolates that possess both erm(B) and mef, primarily due to serotype 19A isolates.
Liang, Yu-Jie; Wang, Hui-Ping; Long, Ding-Xin; Li, Wei; Wu, Yi-Jun
Type I and II pyrethroid insecticides display different neurotoxicity. To investigate the long-term (60 days exposure) metabolic effect of the two types of pyrethroid insecticides deltamethrin and permethrin, (1)H nuclear magnetic resonance (NMR) spectroscopy-based metabonomics was used to analyze the biochemical composition of urine and serum samples from rats administrated daily with deltamethrin or permethrin for 60 consecutive days, and principal component analysis used to visualize similarities and differences in the resultant biochemical profiles. Rats treated with either deltamethrin or permethrin displayed increased levels of urinary acetate, dimethylamine, dimethylglycine, trimethylamine and serum free amino acids, and decreased urinary 2-oxoglutarate, all of which are indicative of kidney lesions and nephrotoxicity. The reduced excretion of tricarboxylic acid cycle intermediates, together with increased 3-D-hydroxybutyrate, acetate, and lactate in treated rats could suggest disturbance of the energy metabolism, including an increased rate of anaerobic glycolysis, enhanced fatty acid β-oxidation and ketogenesis. These results show that these two types of insecticides have similarities in the urine and serum spectra, indicating that similar metabolic pathways are perturbed by the insecticides, which induced hepatotoxicity and nephrotoxicity. This approach may lead to the discovery of novel biomarkers of pyrethroids toxicity and thereby provide new insights into the toxicological mechanisms of pesticides pyrethroids.
Srisawat, Raweewan; Komalamisra, Narumon; Apiwathnasorn, Chamnarn; Paeporn, Pungasem; Roytrakul, Sittiruk; Rongsriyam, Yupha; Eshita, Yuki
One of the mechanisms responsible for pyrethroid resistance in mosquitoes is mutations in domain IIS6 of voltage-gated sodium channel gene (kdr). Aedes aegypti larvae were collected from the central provinces of Thailand (Bangkok, Prachin Buri and Ratchaburi) and colonized until they became adults. Partial fragment of kdr of permethrin-resistant mosquitoes were amplified by RT-PCR and sequenced. Among the four nucleotide mutations detected, two mutations resulted in two amino acid substitutions, S(TCC) 989 P(CCC) and V(GTA)1016 G(GGA). Among 94 permethrin-resistant mosquitoes, the SS genotype (SS/VV) was found to predominate (n = 74), followed by SR (SP/VG) (n = 15) and RR (PP/ GG) genotypes (n = 5), with the resistant allele frequency ranging from 0.03 to 0.17. As pyrethroid insecticides are currently being advocated for use in Thailand, investigations of pyrethroid resistance in other regions of the country are needed to prevent potential cross-resistance among different types of insecticides.
El Chartouni, Léa; Randoux, B; Duyme, F; Renard-Merlier, D; Tisserant, B; Bourdon, N; Pillon, V; Sanssené, J; Durand, R; Halama, P; Reignault, Ph
The aim of this study was to investigate the infection process of M. graminicola and the defence mechanisms related to active oxygen species (AOS) in five French wheat cultivars. These cultivars exhibited various resistant levels to M. graminicola infection: Maxyl, Caphorn and Gen11 are susceptible cultivars, whereas Capnor and Gen23 show high levels of quantitative resistances. In addition, Capnor, Gen23 and Gen11 are tolerant cultivars, i.e., their yield performance was less affected by infection compared to non-tolerant cultivars. Cultivars were inoculated with the IPO323 reference M. graminicola strain. First wheat leaves were collected 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 days after inoculation. The cytological and antioxidant response of the cultivars were both studied over the whole time course. Although infection occurred mainly through stomata, direct penetration attempts were also scored. Moreover, papilla formation turned out to be very rare. Assays for changes in peroxydase (PO), glutathione-S-transferase (GST) and lipoxygenase (LOX) activities allowed us to compare their levels in the five French wheat cultivars regarding to their resistance and/or tolerance towards M. graminicola infection. PO and GST were correlated to necrosis probably as a consequence of detoxification and LOX was related to some of the germination process steps. We also showed that significant differences for several biochemical parameters exist between the studied cultivars in non inoculated conditions but these differences were less important in the presence of the fungus.
Mark W Douglas; Jacob George
It is now widely recognized that chronic hepatitis C (CHC) is associated with insulin resistance (IR) and type 2 diabetes, so can be considered a metabolic disease. IR is most strongly associated with hepatitis C virus (HCV) genotype 1, in contrast to hepatic steatosis, which is associated with genotype 3 infection. Apart from the well-described complications of diabetes, IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma. More recently, it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined. This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.
Soga, Kouichi; Yano, Sachiko; Matsumoto, Shouhei; Hoson, Takayuki
Hypergravity generated by centrifugal acceleration is the only practical method to modify the magnitude of gravitational acceleration for a sufficient duration on Earth and has been used to analyze the nature and mechanism of graviresponse, particularly gravity resistance, in plants. Plant organs are generally resistant to gravitational acceleration. Hypergravity produced from centrifugation speeds in the range of 10-300 × g, which is easily produced by a benchtop centrifuge, is often used during plant experiments. After centrifugation, the plant material is fixed with suitable fixatives in appropriate sample storage containers such as the Chemical Fixation Bag. The material is then analyzed with a variety of methods, depending on the purpose of the experiment. Plant material fixed with the RNAlater(®) solution can be sequentially used for determining the mechanical properties of the cell wall, for RNA extraction (which is necessary for gene expression analysis), for estimating the enzyme activity of the cell wall proteins, and for determining the levels as well as the compositions of cell wall polysaccharides. The plant material can also be used directly for microscopic observation of cellular components such as cortical microtubules.
Huynh, Carolyn K; Poquette, Signe R; Whitlow, W Lindsay
The present study sought to evaluate the behavioral responses of non-target organisms in order to determine whether phototactic responses of isopods to danger cues are altered as a function of exposure to the pyrethroid pesticides λ-cyhalothrin and bifenthrin. Experiments conducted on Gnorimosphaeroma oregonensis identified sublethal behavioral responses to pyrethroids, λ-cyhalothrin and bifenthrin at concentrations 0.15 ng/mL, 0.025 ng/mL, and 0.005 ng/mL. Experimental setup tested isopod phototactic responses across six treatments: control, pyrethroid, hemolymph, predator, hemolymph + pyrethroid, and predator + pyrethroid. Isopods exhibited no preference for phototactic responses in the control and pyrethroid treatments. When exposed to danger cues (hemolymph or predator), isopods exhibited significant negative phototaxis, as expected. When exposure to danger cues was combined with pyrethroids, isopods again exhibited no preference for phototactic response. Experiments indicate that pyrethroids diminish isopod's negatively phototactic response to danger cues.
Pyrethroid insecticides bind to voltage-gated sodium channels and modify their gating kinetics, thereby disrupting neuronal function. Using murine neocortical neurons in primary culture, we have compared the ability of 11 structurally diverse pyrethroid insecticides to evoke Na+ ...
Full Text Available Viruses depend on cell metabolism for their own propagation. The need to foster an intimate relationship with the host has resulted in the development of various strategies designed to help virus escape from the defense mechanisms present in the host. Over millions of years, the unremitting battle between pathogens and their hosts has led to changes in evolution of the immune system. Snake venoms are biological resources that have antiviral activity, hence substances of significant pharmacological value. The biodiversity in Brazil with respect to snakes is one of the richest on the planet; nevertheless, studies on the antiviral activity of venom from Brazilian snakes are scarce. The antiviral properties of snake venom appear as new promising therapeutic alternative against the defense mechanisms developed by viruses. In the current study, scientific papers published in recent years on the antiviral activity of venom from various species of snakes were reviewed. The objective of this review is to discuss the mechanisms of resistance developed by viruses and the components of snake venoms that present antiviral activity, particularly, enzymes, amino acids, peptides and proteins.
It is found that the incorporation of Nitrite Corrosion Inhibitor (NCI) greatly weakens the resistance of mixtures to sulfate attack.To study the mechanism of this phenomenon,in this paper,the influence of NCI additionon on the cement paste and microstructure change of high performance concrete specimens is studied by means of quantitative XRD,SEM tests.The results demonstrate that the incorporation of NCI accelerates the formation of calcium hydroxide and ettringite crystals,and weakens the pore refinement effect caused by the secondary hydration reaction of fly ash and microsilica.At the age up to one year,the relative crystal quantity in mixture containing NCI is always higher than that in control mixture.The reasons for the degradation in sulfate resisitance of mixtures may be attributed to the increase and stability of the calcium hydroxide and ettringite crystals formed and the weakening of secondary hydration reaction.Based on the results,conclusion can be drawn that NCI should be used cautiously in practical engineering where high resistance to sulfate attack is required.
Francois X. Claret
Full Text Available HER2-postitive breast cancer has the second-poorest prognosis among breast cancer subtypes. One of the most effective targeted therapies for patients with HER2-positive breast cancer is trastuzumab-based. However, primary or acquired resistance to trastuzumab has been a major obstacle in the clinical management of this disease. Therefore, to better control HER2-postitive breast cancer, it is necessary to gain a deeper understanding of trastuzumab’s actions and the pathways that cancer cells use to dodge its effects. In this review, we attempt to give an overview of the widely accepted and currently proposed molecular mechanisms for these actions and highlight recent advances in our understanding of HER2 targeted therapies.
Camps, S.M.T.; Rijs, A.J.M.M.; Klaassen, C.H.; Meis, J.F.G.M.; O'Gorman, C.M.; Dyer, P.S.; Melchers, W.J.G.; Verweij, P.E.
A rapid emergence of azole resistance has been observed in Aspergillus fumigatus in The Netherlands over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves the TR(34)/L98H mutations in cyp51A. This resistance mechanism is now also increasingly being
Full Text Available Abstract The identification of a point mutation in voltage-gated sodium channel gene was conducted on the major of dengue vector Aedes aegypti from Simongan Village, Semarang Municypality Central Java, which occurred to be resistant toward malathion and cypermethrin base on WHO methodology standard (impregnated paper. The objectives of this studi was to identify the point mutation on the codon 1014 of voltage gated sodium channel gene of Ae. aegypti mosquitoes which was associated with the vector resistance of pyrethroid group. The detection of a point mutation of voltage-gated sodium channel was conducted using DNA extraction and semi nested polymerase chain reaction (PCR amplification of the mosquitoes resistant strain. The susceptibility test (as a screening resistant phenotype showed that few samples of Ae. aegypti from Simongan Village, Semarang Municypality Central Java resistant to malathion 0,8 % ( organophosphate group and cypermethrin 0,25 % (pyrethroid group. The sequencing result showed that there has been a mutation from the leucine (TTA which turned to be phenylalanin (TTT (kdr-w type on the codon 1014 at the voltage gated sodium channel gene of Ae. aegypti mosquitoes from Simongan Village, Semarang Municypality Central Java, which was associated with the pyrethroid insecticide resistance. There were 78 % mosquitoes which brought mutation alel kdr-w type on the codon 1014 F. Therefore dengue vector control activities should not use any pyrethroid insecticide group. Key Words : Resistance, Aedes aegypti, Voltage Gated Sodium Channel (VGSC, Point Mutation. Abstrak Identifikasi mutasi noktah pada gen Voltage Gated Sodium Channel (VGSC telah dilakukan pada nyamuk Aedes aegypti dari Kelurahan Simongan Kota Semarang, yang telah resisten terhadap insektisida Malathion dan Cypermethrin pada screening susceptibility test (Standar WHO Impregnated paper. Tujuan penelitian adalah untuk mendeteksi
Full Text Available Malaria causes more than 300 million clinical cases and 665,000 deaths each year, and the majority of the mortality and morbidity occurs in sub-Saharan Africa. Due to the lack of effective vaccines and wide-spread resistance to antimalarial drugs, mosquito control is the primary method of malaria prevention and control. Currently, malaria vector control relies on the use of insecticides, primarily pyrethroids. The extensive use of insecticides has imposed strong selection pressures for resistance in the mosquito populations. Consequently, resistance to pyrethroids in Anopheles gambiae, the main malaria vector in sub-Saharan Africa, has become a major obstacle for malaria control. A key element of resistance management is the identification of resistance mechanisms and subsequent development of reliable resistance monitoring tools. Field-derived An. gambiae from Western Kenya were phenotyped as deltamethrin-resistant or -susceptible by the standard WHO tube test, and their expression profile compared by RNA-seq. Based on the current annotation of the An. gambiae genome, a total of 1,093 transcripts were detected as significantly differentially accumulated between deltamethrin-resistant and -susceptible mosquitoes. These transcripts are distributed over the entire genome, with a large number mapping in QTLs previously linked to pyrethorid resistance, and correspond to heat-shock proteins, metabolic and transport functions, signal transduction activities, cytoskeleton and others. The detected differences in transcript accumulation levels between resistant and susceptible mosquitoes reflect transcripts directly or indirectly correlated with pyrethroid resistance. RNA-seq data also were used to perform a de-novo Cufflinks assembly of the An. gambiae genome.
Cavalcanti, Felipe Lira de Sá; Mirones, Cristina Rodríguez; Paucar, Elena Román; Montes, Laura Álvarez; Leal-Balbino, Tereza Cristina; de Morais, Marcia Maria Camargo; Martínez-Martínez, Luis; Ocampo-Sosa, Alain Antonio
An investigation was carried out into the genetic mechanisms responsible for multidrug resistance in nine carbapenem-resistant Pseudomonas aeruginosaisolates from different hospitals in Recife, Brazil. Susceptibility to antimicrobial agents was determined by broth microdilution. Polymerase chain reaction (PCR) was employed to detect the presence of genes encoding β-lactamases, aminoglycoside-modifying enzymes (AMEs), 16S rRNA methylases, integron-related genes and OprD. Expression of genes coding for efflux pumps and AmpC cephalosporinase were assessed by quantitative PCR. The outer membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The blaSPM-1, blaKPC-2 and blaGES-1 genes were detected in P. aeruginosaisolates in addition to different AME genes. The loss of OprD in nine isolates was mainly due to frameshift mutations, premature stop codons and point mutations. An association of loss of OprD with the overexpression of MexAB-OprM and MexXY-OprM was observed in most isolates. Hyper-production of AmpC was also observed in three isolates. Clonal relationship of the isolates was determined by repetitive element palindromic-PCR and multilocus sequence typing. Our results show that the loss of OprD along with overexpression of efflux pumps and β-lactamase production were responsible for the multidrug resistance in the isolates analysed. PMID:26676375
Seyama, Shoji; Wajima, Takeaki; Nakaminami, Hidemasa; Noguchi, Norihisa
The aim of this study was to clarify the clarithromycin resistance mechanisms of β-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae strains. In all clarithromycin-resistant strains, the transcript level of acrB was significantly elevated, and these strains had a frameshift mutation in acrR Introduction of the acrR mutation into H. influenzae Rd generated a clarithromycin-resistant transformant with the same MIC as the donor strain. Our results indicate that the acrR mutation confers clarithromycin resistance by the increasing the transcription of acrB.
Population-based estimates of pesticide intake are needed to characterize exposure for particular demographic groups based on their dietary behaviors. Regression modeling performed on measurements of selected pesticides in composited duplicate diet samples allowed (1) estimation of pesticide intakes for a defined demographic community, and (2) comparison of dietary pesticide intakes between the composite and individual samples. Extant databases were useful for assigning individual samples to composites, but they could not provide the breadth of information needed to facilitate measurable levels in every composite. Composite sample measurements were found to be good predictors of pyrethroid pesticide levels in their individual sample constituents where sufficient measurements are available above the method detection limit. Statistical inference shows little evidence of differences between individual and composite measurements and suggests that regression modeling of food groups based on composite dietary samples may provide an effective tool for estimating dietary pesticide intake for a defined population. The research presented in the journal article will improve community's ability to determine exposures through the dietary route with a less burdensome and costly method.
Brausch, John M; Smith, Philip N
Extensive pesticide usage in the Southern High Plains has led to the development of resistance in many pest species, as well as some non-target organisms. Thamnocephalus platyurus derived from agriculturally impacted watersheds are between two and three times less sensitive to commonly applied agrochemicals than T. platyurus from native grassland watersheds. Biological mechanisms that convey such resistance are currently unknown. This study identified the contribution of metabolic enzymes to T. platyurus pesticide resistance using the synergists piperonyl butoxide (PBO) and S,S,S-tributyl phosphorotrithioate (DEF) to inhibit cytochrome P450s or hydrolases, respectively. Inhibition of cytochrome P450s and hydrolases partially restored cyfluthrin and DDT sensitivity in T. platyurus, suggesting other resistance inferring mechanism(s) were also involved. However, inhibition of hydrolases with DEF completely restored methyl parathion sensitivity in pesticide resistant T. platyurus. DDT resistance paralleled cyfluthrin resistance, but did not for methyl parathion resistance. These data suggest that the primary mechanism for the development of resistance to agrochemicals in T. platyurus is due to increased metabolic detoxification.
Resistance to macrolide-lincosamide-streptogramin (MLS) group antibiotics in the dairy bacterium Streptococcus thermophilus (ST) is documented but the mechanism of resistance has not been elucidated. MIC values for erythromycin (Erm), azithromycin (Azm), tylosin (Tyl), spiramycin (Spm), pristinamyci...
Cristina Mónica Montagna
Full Text Available Black flies, a non-target species of the insecticides used in fruit production, represent a severe medical and veterinary problem. Large increases in the level of resistance to the pyrethroids fenvalerate (more than 355-fold and deltamethrin (162-fold and a small increase in resistance to the organophosphate azinphos methyl (2-fold were observed between 1996-2008 in black fly larvae under insecticide pressure. Eventually, no change or a slight variation in insecticide resistance was followed by a subsequent increase in resistance. The evolution of pesticide resistance in a field population is a complex and stepwise process that is influenced by several factors, the most significant of which is the insecticide selection pressure, such as the dose and frequency of application. The variation in insecticide susceptibility within a black fly population in the productive area may be related to changes in fruit-pest control. The frequency of individuals with esterase activities higher than the maximum value determined in the susceptible population increased consistently over the sampling period. However, the insecticide resistance was not attributed to glutathione S-transferase activity. In conclusion, esterase activity in black flies from the productive area is one mechanism underlying the high levels of resistance to pyrethroids, which have been recently used infrequently. These enzymes may be reselected by currently used pesticides and enhance the resistance to these insecticides.
Aldana-Madrid, Maria L; Valenzuela-Quintanar, Ana I; Silveira-Gramont, Maria I; Rodríguez-Olibarría, Guillermo; Grajeda-Cota, Patricia; Zuno-Floriano, Fabiola G; Miller, Marion G
This study was conducted to evaluate the presence of cyhialothrin, cyfluthrin, cypermethrin, fenvalerate, and deltamethrin in vegetables produced and consumed in Sonora, Mexico. A total of 345 samples were collected from cluster sampling of markets and fields. Approximately 9% of the samples tested positive for pyrethroids (residue range 0.004-0.573 mg kg(-1)). Based on the results, the potential toxicological risk of human exposure to the pyrethroid insecticides measured in vegetables appears to be minimal, with the estimated exposure being 1,000 times lower than admissible levels.
Holger B. Deising
Full Text Available In this review article, we show that occurrence of fungicide resistance is one of the most important issues in modern agriculture. Fungicide resistance may be due to mutations of genes encoding fungicide targets (qualitative fungicide resistance or to different mechanisms that are induced by sub-lethal fungicide stress. These mechanisms result in different and varying levels of resistance (quantitative fungicide resistance. We discuss whether or not extensive use of fungicides in agricultural environments is related to the occurrence of fungicide resistance in clinical environments. Furthermore, we provide recommendations of how development of fungicide resistant pathogen populations may be prevented or delayed.A ocorrência de resistência a fungicidas é uma das mais importantes conseqüências da agricultura moderna. Este fato pode ser resultado de mutações em genes codificadores de resistência a fungicidas (resistência quantitativa ou a diferentes mecanismos que são induzidos por stresse devido a doses subletais dos produtos utilizados. Estes mecanismos produzem diferentes e variados níveis de resistência (resistência quantitativa. Também é discutido se o uso extensivo de fungicidas em ambientes agricultáveis é relacionado ou não com a ocorrência de resistência em ambientes clínicos. Além disso, também são fornecidas recomendações de como prevenir ou mesmo retardar o desenvolvimento de resistência a fungicidas em patógenos.
Oduola Adedayo O
Full Text Available Abstract Background Resistance monitoring is essential in ensuring the success of insecticide based vector control programmes. This study was carried out to assess the susceptibility status of urban populations of Anopheles gambiae to carbamate insecticide being considered for vector control in mosquito populations previously reported to be resistant to DDT and permethrin. Methods Two – three day old adult female Anopheles mosquitoes reared from larval collections in 11 study sites from Local Government Areas of Lagos were exposed to test papers impregnated with DDT 4%, deltamethrin 0.05% and propoxur 0.1% insecticides. Additional tests were carried out to determine the susceptibility status of the Anopheles gambiae population to bendiocarb insecticide. Members of the A. gambiae complex, the molecular forms, were identified by PCR assays. The involvement of metabolic enzymes in carbamate resistance was assessed using Piperonyl butoxide (PBO synergist assays. The presence of kdr-w/e and ace-1R point mutations responsible for DDT-pyrethroid and carbamate resistance mechanisms was also investigated by PCR. Results Propoxur resistance was found in 10 out of the 11 study sites. Resistance to three classes of insecticides was observed in five urban localities. Mortality rates in mosquitoes exposed to deltamethrin and propoxur did not show any significant difference (P > 0.05 but was significantly higher (P A. gambiae s.s (M form. The kdr -w point mutation at allelic frequencies between 45%-77% was identified as one of the resistant mechanisms responsible for DDT and pyrethroid resistance. Ace-1R point mutation was absent in the carbamate resistant population. However, the possible involvement of metabolic resistance was confirmed by synergistic assays conducted. Conclusion Evidence of carbamate resistance in A. gambiae populations already harbouring resistance to DDT and permethrin is a clear indication that calls for the implementation of
Vaidyanathan, Aparajitha; Sawers, Lynne; Gannon, Anne-Louise; Chakravarty, Probir; Scott, Alison L; Bray, Susan E; Ferguson, Michelle J; Smith, Gillian
Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays. Paclitaxel-resistant cells were cross-resistant to olaparib, doxorubicin and rucaparib but not to veliparib or AZD2461. Resistance correlated with increased ABCB1 expression and was reversible following treatment with the ABCB1 inhibitors verapamil and elacridar. Active efflux of paclitaxel, olaparib, doxorubicin and rucaparib was confirmed in drug-resistant cells and in ABCB1-expressing bacterial membranes. We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients.
Du, Yuzhe; Nomura, Yoshiko; Luo, Ningguang; Liu, Zhiqi; Lee, Jung-Eun; Khambay, Bhupinder; Dong, Ke
Pyrethroid insecticides are classified as type I or type II based on their distinct symptomology and effects on sodium channel gating. Structurally, type II pyrethroids possess an alpha-cyano group at the phenylbenzyl alcohol position, which is lacking in type I pyrethroids. Both type I and type II pyrethroids inhibit deactivation consequently prolonging the opening of sodium channels. However, type II pyrethroids inhibit the deactivation of sodium channels to a greater extent than type I pyrethroids inducing much slower decaying of tail currents upon repolarization. The molecular basis of a type II-specific action, however, is not known. Here we report the identification of a residue G(1111) and two positively charged lysines immediately downstream of G(1111) in the intracellular linker connecting domains II and III of the cockroach sodium channel that are specifically involved in the action of type II pyrethroids, but not in the action of type I pyrethroids. Deletion of G(1111), a consequence of alternative splicing, reduced the sodium channel sensitivity to type II pyrethroids, but had no effect on channel sensitivity to type I pyrethroids. Interestingly, charge neutralization or charge reversal of two positively charged lysines (Ks) downstream of G(1111) had a similar effect. These results provide the molecular insight into the type II-specific interaction of pyrethroids with the sodium channel at the molecular level.
Mahamat, Aba; Bertrand, Xavier; Moreau, Brigitte; Hommel, Didier; Couppie, Pierre; Simonnet, Christine; Kallel, Hatem; Demar, Magalie; Djossou, Felix; Nacher, Mathieu
This study investigated the clinical epidemiology and resistance mechanisms of Acinetobacter baumannii and characterised the clonal diversity of carbapenem-resistant A. baumannii (CRAB) during an ICU-associated outbreak at Cayenne Hospital, French Guiana. All non-duplicate A. baumannii isolates from 2008 to 2014 were tested for antibiotic susceptibility by disk diffusion. Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on CRAB. Of the 441 A. baumannii isolates, most were from males (54.0%) and were detected mainly from the ICU (30.8%) and medicine wards (21.8%). In the ICU, strains were mainly isolated from the respiratory tract (44.1%) and bloodstream (14.0%), whereas in medicine wards they mainly were from wound/drainage (36.5%) and bloodstream (25.0%). A. baumannii showed the greatest susceptibility to piperacillin/tazobactam (92.7%), imipenem (92.5%), colistin (95.6%) and amikacin (97.2%), being lower in the ICU and medicine wards compared with other wards. An outbreak of OXA-23-producing CRAB occurred in the 13-bed ICU in 2010. CRAB strains were more co-resistant to other antimicrobials compared with non-CRAB. Molecular genetics analysis revealed five sequence types [ST78, ST107 and ST642 and two new STs (ST830 and ST831)]. Analysis of PFGE profiles indicated cross-transmissions of CRAB within the ICU, between the ICU and one medicine ward during transfer of patients, and within that medicine ward. This study provides the first clinical and molecular data of A. baumannii from French Guiana and the Amazon basin. The ICU was the highest risk unit of this nosocomial outbreak of OXA-23-producing CRAB, which could subsequently disseminate within the hospital.
Fernández-Aparicio, Mónica; Prats, Elena; Emeran, Amero A; Rubiales, Diego
Beet powdery mildew incited by Erysiphe betae is a serious foliar fungal disease of worldwide distribution causing losses of up to 30%. In the present work, we searched for resistance in a germplasm collection of 184 genotypes of Beta vulgaris including fodder (51 genotypes), garden (60 genotypes), leaf (51 genotypes), and sugar (22 genotypes) beet types. Resistant genotypes were identified in the four beet types under study. In addition, mechanisms underlying resistance were dissected through histological studies. These revealed different resistance mechanisms acting at different fungal developmental stages, i.e., penetration resistance, early and late cell death, or posthaustorial resistance. Most genotypes were able to hamper fungal development at several stages. The later are interesting for breeding aiming to resistance durability. Furthermore, characterization of defense mechanisms will be useful for further cellular and molecular studies to unravel the bases of resistance in this species.
Full Text Available The environment, and especially fresh water, constitutes a reactor where the evolution and the rise of new resistances occur. In rivers or streams, bacteria from different sources such as urban, industrial and agricultural waste, probably selected by intensive antibiotic usage, are collected and mixed with environmental species. This may cause two effects on the development of antibiotic resistances: First, the contamination of water by antibiotics or other pollutants lead to the rise of resistance due to selection processes. For instance, of strains over-expressing broad range defensive mechanisms, such as efflux pumps. Second, since environmental species are provided with intrinsic antibiotic resistance mechanisms, the mixture with allochthonous species is likely to cause genetic exchange. In this context, the role of phages and integrons for the spread of resistance mechanisms appears significant. Allochthonous species could acquire new resistances from environmental donors and introduce the newly acquired resistance mechanisms into the clinics. This is illustrated by clinically relevant resistance mechanisms, such as the fluoroquinolones resistance genes qnr. Freshwater appears to play an important role in the emergence and in the spread of antibiotic resistances, highlighting the necessity for strategies of water quality improvement. Moreover, further knowledge is needed to better understand the role of the environment as reservoir of antibiotic resistances and to assess the risk of spread of antibiotic resistances via water bodies.
Castro, Ana Valeria B.; Kolka, Cathryn M.; Kim, Stella P.; Bergman, Richard N.
Overall excess of fat, usually defined by the body mass index, is associated with metabolic (e.g. glucose intolerance, type 2 diabetes mellitus (T2DM), dyslipidemia) and non-metabolic disorders (e.g. neoplasias, polycystic ovary syndrome, non-alcoholic fat liver disease, glomerulopathy, bone fragility etc.). However, more than its total amount, the distribution of adipose tissue throughout the body is a better predictor of the risk to the development of those disorders. Fat accumulation in the abdominal area and in non-adipose tissue (ectopic fat), for example, is associated with increased risk to develop metabolic and non-metabolic derangements. On the other hand, observations suggest that individuals who present peripheral adiposity, characterized by large hip and thigh circumferences, have better glucose tolerance, reduced incidence of T2DM and of metabolic syndrome. Insulin resistance (IR) is one of the main culprits in the association between obesity, particularly visceral, and metabolic as well as non-metabolic diseases. In this review we will highlight the current pathophysiological and molecular mechanisms possibly involved in the link between increased VAT, ectopic fat, IR and comorbidities. We will also provide some insights in the identification of these abnormalities. PMID:25211442
Hossain, Muhammad Mubarak; Suzuki, Tadahiko; Unno, Toshihiro; Komori, Seiichi; Kobayashi, Haruo
This study was designed to investigate the effects of several pyrethroids on the extracellular level of glutamate and gamma-aminobutyric acid (GABA) in the hippocampus of rats measured using microdialysis following systemic (i.p.) administration. Pyrethroids, allethrin (type I), cyhalothrin (type II) and deltamethrin (type II), were found to have differential effects on glutamatergic and GABAergic neurons in the hippocampus. Allethrin had an interesting dual effect, increasing glutamate release with low doses (10 and 20mg/kg) to about 175-150% and decreasing glutamate release with high dose (60 mg/kg) to about 50% of baseline. Cyhalothrin (10, 20 and 60 mg/kg) inhibited the release of glutamate dose-dependently to about 60-30% of baseline. The extracellular level of GABA was decreased to about 50% of baseline by 10 and 20mg/kg allethrin. The high dose of allethrin (60 mg/kg) and all doses of cyhalothrin (10, 20 and 60 mg/kg) increased the extracellular level of GABA while decreasing the level of glutamate. Deltamethrin dose-dependently increased extracellular glutamate levels to about 190-275% of baseline while decreasing the level of GABA. Local infusion of TTX (1 microM), a Na(+) channel blocker, completely prevented the effect of allethrin (10, 20 an