Emerging mosquito resistance to piperonyl butoxide-synergized pyrethroid insecticide and its mechanism

Piperonyl butoxide (PBO)-synergized pyrethroid products are widely available for the control of pyrethroid-resistant mosquitoes. To date, no study has formally examined mosquito resistance to PBO-synergized insecticides. We used Culex quinquefasciatus as a model mosquito examined the insecticide resistance mechanisms of mosquitoes to PBO-synergized pyrethroid using modified World Health Organization tube bioassays and biochemical analysis of metabolic enzyme expressions prior- and post-PBO exposure. We measured mosquito mortalities and metabolic enzyme expressions in mosquitoes with/without pre-exposure to different PBO concentrations and exposure durations. We found that field Culex quinquefasciatus mosquitoes were resistant to all insecticides tested, including PBO-synergized pyrethroids (mortality ranged from 3.7±4.7% to 66.7±7.7%), except malathion. Field mosquitoes had elevated levels of carboxylesterase (COE, 3.8-fold) and monooxygenase (P450, 2.1-fold) but not glutathione S-transferase (GST) compared to susceptible mosquitoes. When the field mosquitoes were pre-exposed to 4% PBO, the 50% lethal concentration of deltamethrin was reduced from 0.22% to 0.10%, compare to 0.02% for susceptible mosquitoes. Knockdown resistance gene mutation (L1014F) rate was 62% in field mosquitoes. PBO pre-exposure suppressed P450 enzyme expression levels by 25~34%, GST by 11%, and had no impact on COE enzyme expression. Even with the optimal PBO concentration and exposure duration, field mosquitoes had significantly higher P450 enzyme expression levels after PBO exposure compared to laboratory controls. These results demonstrate that PBO alone may not be enough to control highly pyrethroid resistant mosquitoes due to the multiple resistance mechanisms. Mosquito resistance to PBO-synergized insecticide should be closely monitored.

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Insecticide Resistance in Anopheles stephensi in Somali Region, Eastern Ethiopia

10.21203/rs.2.18020/v2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Solomon Yared ◽

Araya Gebressielasie ◽

Lambodhar Damodaran ◽

Victoria Bonnell ◽

Karen Lopez ◽

...

Keyword(s):

Insecticide Resistance ◽

Anopheles Stephensi ◽

Mortality Rates ◽

Resistance Mechanisms ◽

World Health ◽

Malaria Vectors ◽

Eastern Ethiopia ◽

Pyrethroid Insecticides ◽

Pirimiphos Methyl ◽

Health Organization

Abstract Background: The movement of malaria vectors into new areas is a growing concern in the efforts to control malaria. The recent report of Anopheles stephensi in eastern Ethiopia has raised the necessity to understand the insecticide resistance status of the vector in the region to better inform vector-based interventions. The aim of this study was to evaluate insecticide resistance in An. stephensi in eastern Ethiopia using two approaches: 1) World Health Organization (WHO) bioassay tests in An. stephensi and 2) genetic analysis of insecticide resistance genes in An. stephensi in eastern Ethiopia. Methods: Mosquito larvae and pupae were collected from Kebridehar. Insecticide susceptibility of An. stephensi was tested with malathion 5%, bendiocarb 0.1%, propoxur 0.1%, deltamethrin 0.05%, permethrin 0.75%, Pirimiphos-methyl 0.25% and DDT 4%, according to WHO standard protocols. Results: All An. stephensi samples were resistant to carbamates, with mortality rates 23% and 21% for bendiocarb and propoxur, respectively. Adult An. stephensi was also resistant to pyrethroid insecticides with mortality rates 67% for deltamethrin and 53% for permethrin. Resistance to DDT and malathion was detected in An. stephensi with mortality rates of 32% as well as An. stephensi was resistance to pirimiphos-methyl with mortality rates 14%. Analysis of the voltage gate sodium channel gene (vgsc) revealed the absence of kdr L1014 mutations. Conclusion: Overall, these findings support that An. stephensi is resistant to several classes of insecticides, most notably pyrethroids. However, the absence of the kdr L1014 gene may suggest non-target site resistance mechanisms. Continuous insecticide resistance monitoring should be carried out in the region to confirm the documented resistance and exploring mechanisms conferring resistance in An. stephensi in Ethiopia.

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Evaluating insecticide resistance across African districts to aid malaria control decisions

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2006781117 ◽

2020 ◽

Vol 117 (36) ◽

pp. 22042-22050 ◽

Cited By ~ 1

Author(s):

Catherine L. Moyes ◽

Duncan K. Athinya ◽

Tara Seethaler ◽

Katherine E. Battle ◽

Marianne Sinka ◽

...

Keyword(s):

Cytochrome P450 ◽

Pyrethroid Resistance ◽

Resistance Mechanisms ◽

World Health ◽

Malaria Vector Control ◽

Ensemble Model ◽

Metabolic Resistance ◽

The World ◽

Susceptibility Tests ◽

Health Organization

Malaria vector control may be compromised by resistance to insecticides in vector populations. Actions to mitigate against resistance rely on surveillance using standard susceptibility tests, but there are large gaps in the monitoring data across Africa. Using a published geostatistical ensemble model, we have generated maps that bridge these gaps and consider the likelihood that resistance exceeds recommended thresholds. Our results show that this model provides more accurate next-year predictions than two simpler approaches. We have used the model to generate district-level maps for the probability that pyrethroid resistance inAnopheles gambiaes.l. exceeds the World Health Organization thresholds for susceptibility and confirmed resistance. In addition, we have mapped the three criteria for the deployment of piperonyl butoxide-treated nets that mitigate against the effects of metabolic resistance to pyrethroids. This includes a critical review of the evidence for presence of cytochrome P450-mediated metabolic resistance mechanisms across Africa. The maps for pyrethroid resistance are available on the IR Mapper website, where they can be viewed alongside the latest survey data.

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Changes in Gene Expression in PBMCs Profiles of PPARα Target Genes in Obese and Non-Obese Individuals During Fasting

Annals of Nutrition and Metabolism ◽

10.1159/000367668 ◽

2014 ◽

Vol 66 (1) ◽

pp. 19-25 ◽

Cited By ~ 2

Author(s):

Ingrid Felicidade ◽

Juliana Cristina Marcarini ◽

Clísia Mara Carreira ◽

Marla Karine Amarante ◽

Lydia A. Afman ◽

...

Keyword(s):

Gene Expression ◽

Target Genes ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Obese Group ◽

World Health ◽

Peripheral Blood Mononuclear ◽

Expression Levels ◽

Patients With Diabetes ◽

Health Organization

Background: The prevalence of obesity has risen dramatically and the World Health Organization estimates that 700 million people will be obese worldwide by 2015. Approximately, 50% of the Brazilian population above 20 years of age is overweight, and 16% is obese. Aim: This study aimed to evaluate the differences in the expression of PPARα target genes in human peripheral blood mononuclear cells (PBMCs) and free fatty acids (FFA) in obese and non-obese individuals after 24 h of fasting. We first presented evidence that Brazilian people exhibit expression changes in PPARα target genes in PBMCs under fasting conditions. Methods: Q-PCR was utilized to assess the mRNA expression levels of target genes. Results: In both groups, the FFA concentrations increased significantly after 24 h of fasting. The basal FFA mean concentration was two-fold higher in the obese group compared with the non-obese group. After fasting, all genes evaluated in this study showed increased expression levels compared with basal expression in both groups. Conclusion: However, our results reveal no differences in gene expression between the obese and non-obese, more studies are necessary to precisely delineate the associated mechanisms, particularly those that include groups with different degrees of obesity and patients with diabetes mellitus type 2 because the expression of the main genes that are involved in β-oxidation and glucose level maintenance are affected by these factors. © 2014 S. Karger AG, Basel

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Detection of a novel mutation G511T in the 530 loop in 16S rRNA in multi drugs resistant Mycobacterium tuberculosis isolated from Sudanese patients

10.1101/497628 ◽

2018 ◽

Cited By ~ 1

Author(s):

Yousif Mohammed Alfatih ◽

Abeer Babiker Idris ◽

Hadeel Gassim Hassan ◽

Eman O M Nour ◽

Nihad M A Elhaj ◽

...

Keyword(s):

16S Rrna ◽

Molecular Mechanisms ◽

Novel Mutation ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

World Health ◽

Bacterial Disease ◽

Global Public Health ◽

Mdr Tb ◽

Health Organization

Background: Tuberculosis (TB) is a bacterial disease considered as a global public health emergency by the World Health Organization (WHO) since 1993. In Sudan, MDR-TB represents a growing threat and one of the most important challenges that faced national tuberculosis program to establish a comprehensive multidrug-resistant tuberculosis management system. Objective: To characterize the diversity and frequency of mutations in Sudanese MDR-TB strains isolated from Wad Madani, Al-Gadarif and Khartoum using 16S rRNA and phylogeny approach. Material and Methods: A total of 60 MDR-TB isolates from Wad-Madani, Al-Gadarif and Khartoum were tested with molecular LPA (Genotype MTBDR plus) and GeneXpert MTB/RIF assay and Spoligotyping to confirm their resistance to RIF and INH. Sequencing and phylogenetic analysis was carried out using in silico tools. Result: This study revealed the circulation of different Sudanese MDR-TB strains isolated from Wad Madani and Al-Gadarif belonging to two distinct common ancestors. Two isolates from Wad Madani (isolate3 and isolate11) found in one main group which characterized by a novel mutation G511T in the 530 loop. Conclusion: The recurrence of C217A mutation in Wad Madani (isolate11) indicates the spread of this mutation in Sudanese MDR-TB strains and the diversity of this inheritance leading to generate new G511T novel mutation. So, understanding the molecular characterization of resistance mechanisms in MD-TB can facilitate the early detection of resistance, the choice of appropriate treatment and ultimately the management of MD-TB transmission. Bioinformatics approaches provide helpful tools for analyzing molecular mechanisms of resistance in pathogens.

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Antibiotic resistance trends and mechanisms in the foodborne pathogen,Campylobacter

Animal Health Research Reviews ◽

10.1017/s1466252317000135 ◽

2017 ◽

Vol 18 (2) ◽

pp. 87-98 ◽

Cited By ~ 22

Author(s):

Yizhi Tang ◽

Liangxing Fang ◽

Changyun Xu ◽

Qijing Zhang

Keyword(s):

Antibiotic Resistance ◽

Efflux Pump ◽

Foodborne Pathogen ◽

Resistance Mechanisms ◽

World Health ◽

Antibiotic Resistant ◽

Innovative Strategies ◽

Control And Prevention ◽

Antibiotic Selection Pressure ◽

Health Organization

AbstractCampylobacteris a major foodborne pathogen and is commonly present in food producing animals. This pathogenic organism is highly adaptable and has become increasingly resistant to various antibiotics. Recently, both the Centers for Disease Control and Prevention and the World Health Organization have designated antibiotic-resistantCampylobacteras a serious threat to public health. For the past decade, multiple mechanisms conferring resistance to clinically important antibiotics have been described inCampylobacter, and new resistance mechanisms constantly emerge in the pathogen. Some of the recent examples include theerm(B)gene conferring macrolide resistance, thecfr(C)genes mediating resistance to florfenicol and other antimicrobials, and a functionally enhanced variant of the multidrug resistance efflux pump, CmeABC. The continued emergence of new resistance mechanisms illustrates the extraordinary adaptability ofCampylobacterto antibiotic selection pressure and demonstrate the need for innovative strategies to control antibiotic-resistantCampylobacter. In this review, we will briefly summarize the trends of antibiotic resistance inCampylobacterand discuss the mechanisms of resistance to antibiotics used for animal production and important for clinical therapy in humans. A special emphasis will be given to the newly discovered antibiotic resistance.

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Pyrethroid Susceptibility in Culex quinquefasciatus Say. (Diptera: Culicidae) Populations from Delta State, Niger-Delta Region, Nigeria

Journal of Medical Entomology ◽

10.1093/jme/tjab217 ◽

2022 ◽

Author(s):

Chioma C Ojianwuna ◽

Ahmed I Omotayo ◽

Victor N Enwemiwe ◽

Fouad A Adetoro ◽

Destiny N Eyeboka ◽

...

Keyword(s):

Culex Quinquefasciatus ◽

Niger Delta ◽

World Health ◽

Delta Region ◽

Resistance Development ◽

Vector Borne Diseases ◽

Niger Delta Region ◽

Vector Borne ◽

Health Organization

Abstract The development of insecticide resistance in different species of mosquitoes to Pyrethroids is a major challenge for vector-borne diseases transmitted by mosquitoes. Failure of Pyrethroids in control of mosquitoes would impact negatively on the gains recorded in control of mosquito-borne diseases in previous years. In anticipation of a country-wide deployment of Pyrethroid-treated nets for control of mosquito-borne diseases in Nigeria, this study assessed susceptibility of Culex quinquefasciatus Say. (Diptera: Culicidae) to Pyrethroids in Owhelogbo, Ejeme and Oria-Abraka communities in Delta State, Niger-Delta, Nigeria. Three to five day old Cx. quinquefasciatus were exposed to Deltamethrin (0.05%), Permethrin (0.75%), and Alphacypermethrin (0.05%) using World Health Organization bioassay method. Polymerase chain reaction (PCR) was employed in characterization of species and knockdown mutation. Results revealed that Cx. quinquefasciatus were generally susceptible (98-100%) to Deltamethrin, Permethrin, and Alphacypermethrin in the three communities with the exception of Owhelogbo where resistance to Deltamethrin (97%) was suspected. Knockdown time to Deltamethrin (11.51, 11.23, and 12.68 min), Permethrin (28.75, 13.26, and 14.49 min), and Alphacypermethrin (15.07, 12.50, and 13.03 min) were considerably low for Owhelogbo, Ejeme, and Oria-Abraka Cx. quinquefasciatus populations, respectively. Species identification result showed that all amplified samples were Cx. quinquefasciatus; however, no kdr allele was found in the three populations. Deployment of pyrethroid-treated nets for control of mosquito-borne diseases in Niger-Delta region of Nigeria is capable of reducing burden of diseases transmitted by Cx. quinquefasciatus as well as addressing nuisance value of the vector; however, caution must be entertained so as not to increase selection pressure thereby aiding resistance development.

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Assessment of glutathione S-transferaseM1 (GSTM1) and its polymorphisms GSTM1 null in the response to treatment with chemotherapy in advanced ovarian carcinoma

Einstein (São Paulo) ◽

10.1590/s1679-45082011ao1872 ◽

2011 ◽

Vol 9 (3) ◽

pp. 367-371 ◽

Cited By ~ 1

Author(s):

Gilberto Kendi Takeda ◽

Daniela Batista Leite ◽

Michele Gilvana Junqueira ◽

Luiz Augusto Freire Lopes ◽

Ismael Dale Cotrim Guerreiro da Silva ◽

...

Keyword(s):

Ovarian Cancer ◽

Advanced Ovarian Cancer ◽

World Health ◽

Response To Treatment ◽

Chemotherapy Response ◽

Glutathione S Transferase ◽

Response To Chemotherapy ◽

Chemotherapeutic Treatment ◽

Health Organization ◽

Gstm1 Genotype

ABSTRACT Objective: To assess if the genotype of the glutathione S-transferase M1 (GSTM1) enzyme and its GSTM1 null polymorphism can influence the response to chemotherapeutic treatment of advanced ovarian cancer. Methods: Case-control study of 112 patients with advanced ovarian cancer submitted to chemotherapy during the period from January 1995 to December 2005. The tissue to study the GSTM1 genotype and its deletion came from surgical staging to treat ovarian cancer. The PCR product generates two distinct genotypes, characterized as positive and null. The response to chemotherapy was evaluated using the World Health Organization (WHO) criteria. Patients were classified as having: a) no response, b) a response. Results: The presence of GSTM1 or its GSTM1 null polymorphism did not influence the preoperative chemotherapy response. Among the patients who did respond, 88.9% presented with positive GSTM1 and 11.1% with null GSTM1. Among the patients that did not respond, 85.71% presented with positive GSTM1 and 14.29% with null GSTM1 (p = 0.825). GSTM1 and its GSTM1 null polymorphism had no influence on the postoperative response to chemotherapy. Among the patients who did respond, 80.65% presented with positive GSTM1 and 19.35% with null GSTM1. Among the patients who did not respond, 87.50% presented with positive GSTM1 and 12.5% with the null polymorphism (p = 0.553). Conclusion: No difference was observed in the response to treatment with chemotherapy in patients with advanced ovarian cancer, as to the GSTM1 genotype compared to its GSTM1 null polymorphism.

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MgrB Inactivation Confers Trimethoprim Resistance in Escherichia coli

Frontiers in Microbiology ◽

10.3389/fmicb.2021.682205 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hongmei Shi ◽

Ting Li ◽

Jintian Xu ◽

Jifang Yu ◽

Shanshan Yang ◽

...

Keyword(s):

Escherichia Coli ◽

Gene Knockout ◽

Single Gene ◽

Resistance Mechanisms ◽

Transcriptional Analysis ◽

World Health ◽

Antimicrobial Drugs ◽

Health Organization

After several decades of use, trimethoprim (TMP) remains one of the key access antimicrobial drugs listed by the World Health Organization. To circumvent the problem of trimethoprim resistance worldwide, a better understanding of drug-resistance mechanisms is required. In this study, we screened the single-gene knockout library of Escherichia coli, and identified mgrB and other several genes involved in trimethoprim resistance. Subsequent comparative transcriptional analysis between ΔmgrB and the wild-type strain showed that expression levels of phoP, phoQ, and folA were significantly upregulated in ΔmgrB. Further deleting phoP or phoQ could partially restore trimethoprim sensitivity to ΔmgrB, and co-overexpression of phoP/Q caused TMP resistance, suggesting the involvement of PhoP/Q in trimethoprim resistance. Correspondingly, MgrB and PhoP were shown to be able to modulated folA expression in vivo. After that, efforts were made to test if PhoP could directly modulate the expression of folA. Though phosphorylated PhoP could bind to the promotor region of folA in vitro, the former only provided a weak protection on the latter as shown by the DNA footprinting assay. In addition, deleting the deduced PhoP box in ΔmgrB could only slightly reverse the TMP resistance phenotype, suggesting that it is less likely for PhoP to directly modulate the transcription of folA. Taken together, our data suggested that, in E. coli, MgrB affects susceptibility to trimethoprim by modulating the expression of folA with the involvement of PhoP/Q. This work broadens our understanding of the regulation of folate metabolism and the mechanisms of TMP resistance in bacteria.

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Peering into Avian Influenza A(H5N8) for a Framework towards Pandemic Preparedness

Viruses ◽

10.3390/v13112276 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2276

Author(s):

Joshua Yi Yeo ◽

Samuel Ken-En Gan

Keyword(s):

Avian Influenza ◽

Influenza A ◽

Resistance Mechanisms ◽

Human Infection ◽

World Health ◽

Influenza A Viruses ◽

Host Proteins ◽

Astrakhan Oblast ◽

Health Organization ◽

Wild Waterfowl

2014 marked the first emergence of avian influenza A(H5N8) in Jeonbuk Province, South Korea, which then quickly spread worldwide. In the midst of the 2020–2021 H5N8 outbreak, it spread to domestic poultry and wild waterfowl shorebirds, leading to the first human infection in Astrakhan Oblast, Russia. Despite being clinically asymptomatic and without direct human-to-human transmission, the World Health Organization stressed the need for continued risk assessment given the nature of Influenza to reassort and generate novel strains. Given its promiscuity and easy cross to humans, the urgency to understand the mechanisms of possible species jumping to avert disastrous pandemics is increasing. Addressing the epidemiology of H5N8, its mechanisms of species jumping and its implications, mutational and reassortment libraries can potentially be built, allowing them to be tested on various models complemented with deep-sequencing and automation. With knowledge on mutational patterns, cellular pathways, drug resistance mechanisms and effects of host proteins, we can be better prepared against H5N8 and other influenza A viruses.

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Pseudomonas aeruginosa Susceptibility in Spain: Antimicrobial Activity and Resistance Suppression Evaluation by PK/PD Analysis

Pharmaceutics ◽

10.3390/pharmaceutics13111899 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1899

Author(s):

Ana Valero ◽

Alicia Rodríguez-Gascón ◽

Arantxa Isla ◽

Helena Barrasa ◽

Ester del Barrio-Tofiño ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Activity ◽

Nationwide Survey ◽

Resistance Mechanisms ◽

World Health ◽

Sample Type ◽

Healthcare Associated Infection ◽

Drug Concentrations ◽

Medical Wards ◽

Health Organization

Pseudomonas aeruginosa remains one of the major causes of healthcare-associated infection in Europe; in 2019, 12.5% of invasive isolates of P. aeruginosa in Spain presented combined resistance to ≥3 antimicrobial groups. The Spanish nationwide survey on P. aeruginosa antimicrobial resistance mechanisms and molecular epidemiology was published in 2019. Based on the information from this survey, the objective of this work was to analyze the overall antimicrobial activity of the antipseudomonal antibiotics considering pharmacokinetic/pharmacodynamic (PK/PD) analysis. The role of PK/PD to prevent or minimize resistance emergence was also evaluated. A 10,000-subject Monte Carlo simulation was executed to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) considering the minimum inhibitory concentration (MIC) distribution of bacteria isolated in ICU or medical wards, and distinguishing between sample types (respiratory and non-respiratory). Ceftazidime/avibactam followed by ceftolozane/tazobactam and colistin, categorized as the Reserve by the Access, Watch, Reserve (AWaRe) classification of the World Health Organization, were the most active antimicrobials, with differences depending on the admission service, sample type, and dose regimen. Discrepancies between EUCAST-susceptibility breakpoints for P. aeruginosa and those estimated by PK/PD analysis were detected. Only standard doses of ceftazidime/avibactam and ceftolozane/tazobactam provided drug concentrations associated with resistance suppression.

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