The Effect of Permethrin Resistance on Aedes aegypti Transcriptome Following Ingestion of Zika Virus Infected Blood.
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ABSTRACT:
SUBMITTER: Zhao L
PROVIDER: S-EPMC6165428 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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Project description:Aedes aegypti (L.) is the primary vector of many emerging arboviruses. Insecticide resistance among mosquito populations is a consequence of the application of insecticides for mosquito control. We used RNA-sequencing to compare transcriptomes between permethrin resistant and susceptible strains of Florida Ae. aegypti in response to Zika virus infection. A total of 2,459 transcripts were expressed at significantly different levels between resistant and susceptible Ae. aegypti. Gene ontology analysis placed these genes into 7 categories of biological processes. The 863 transcripts were expressed at significantly different levels between two strains (up/down regulated) more than 2-fold. Quantitative real-time PCR analysis validated Zika-infected response, and suggested a highly overexpressed P450, with AAEL014617 and AAEL006798 as potential candidates for the molecular mechanism of permethrin resistance in Ae. aegypti. Our findings indicated that most detoxification enzymes and immune system enzymes altered their gene expression between the two strains of Ae. aegypti in response to Zika virus infection. Understanding the interactions of arboviruses with resistant mosquito vectors at the molecular level allows for the possible development of new approaches in mitigating arbovirus transmission. This information sheds light on Zika-induced changes in the insecticide resistance of Ae. aegypti with implications for mosquito control strategies.
2018-08-22 | GSE118858 | GEO
Project description:The effect of permethrin resistance on Aedes aegypti transcriptome following ingestion of Zika virus infected blood
| PRJNA487057 | ENA
Project description:Aedes aegypti poses a serious risk to human health due to its wide global distribution, high vector competence for several arboviruses, frequent human biting, and ability to thrive in urban environments. Pyrethroid insecticides remain the primary means of controlling adult A. aegypti populations during disease outbreaks. As a result of decades of use, pyrethroid resistance is a global problem. Cytochrome P450 monooxygenase (CYP)-mediated detoxification is one of the primary mechanisms of pyrethroid resistance. However, the specific CYP(s) responsible for resistance have not been unequivocally determined. We introgressed the resistance alleles from the resistant A. aegypti strain, Singapore (SP), into the genetic background of the susceptible ROCK strain. The resulting strain (CKR) was congenic to ROCK. Our primary goal was to determine which CYPs in SP are linked to resistance. To do this, we first determined which CYPs overexpressed in SP are also overexpressed in CKR, with the assumption that only the CYPs linked to resistance will be overexpressed in CKR relative to ROCK. Next, we determined whether any of the overexpressed CYPs were genetically linked to resistance (cis-regulated) or not (trans-regulated). We found that CYP6BB2, CYP6Z8, CYP9M5 and CYP9M6 were overexpressed in SP as well as in CKR. Based on the genomic sequences and polymorphisms of five single copy CYPs (CYP4C50, 6BB2, 6F2, 6F3 and 6Z8) in each strain, none of these genes were linked to resistance, except for CYP6BB2, which was partially linked to the resistance locus. Hence, overexpression of these four CYPs is due to a trans-regulatory factor(s). Knowledge on the specific CYPs and their regulators involved in resistance is critical for resistance management strategies because it aids in the development of new control chemicals, provides information on potential environmental modulators of resistance, and allows for the detection of resistance markers before resistance becomes fixed in the population.
| S-EPMC6277111 | biostudies-literature
Project description:Aedes aegypti, as one of the vectors transmitting several arboviruses, is the main target in mosquito control programs. Permethrin is used to control mosquitoes and Aedes aegypti get exposed due to its overuse and are now resistant. The increasing percentage of permethrin resistant Aedes aegypti has become an important issue around the world and the potential influence on vectorial capacity needs to be studied. Here we selected a permethrin resistant (p-s) Aedes aegypti population from a wild Florida population and confirmed the resistance ratio to its parental population. We used allele-specific PCR genotyping of the V1016I and F1534C sites in the sodium channel gene to map mutations responsible for the resistance. Two important factors, survival rate and vector competence, that impact vectorial capacity were checked. Results indicated the p-s population had 20 times more resistance to permethrin based on LD50 compared to the parental population. In the genotyping study, the p-s population had more homozygous mutations in both mutant sites of the sodium channel gene. The p-s adults survived longer and had a higher dissemination rate for dengue virus than the parental population. These results suggest that highly permethrin resistant Aedes aegypti populations might affect the vectorial capacity, moreover, resistance increased the survival time and vector competence, which should be of concern in areas where permethrin is applied.
| S-EPMC7830706 | biostudies-literature
Project description:Pyrethroids are one of the few classes of insecticides available to control Aedes aegypti, the major vector of dengue, chikungunya, and Zika viruses. Unfortunately, evolving mechanisms of pyrethroid resistance in mosquito populations threaten our ability to control disease outbreaks. Two common pyrethroid resistance mechanisms occur in Ae. aegypti: 1) knockdown resistance, which involves amino acid substitutions at the pyrethroid target site-the voltage-gated sodium channel (VGSC)-and 2) enhanced metabolism by detoxification enzymes. When a heterogeneous population of mosquitoes is exposed to pyrethroids, different responses occur. During exposure, a proportion of mosquitoes exhibit immediate knockdown, whereas others are not knocked-down and are designated knockdown resistant (kdr). When these individuals are removed from the source of insecticide, the knocked-down mosquitoes can either remain in this status and lead to dead or recover within a few hours. The proportion of these phenotypic responses is dependent on the pyrethroid concentration and the genetic background of the population tested. In this study, we sequenced and performed pairwise genome comparisons between kdr, recovered, and dead phenotypes in a pyrethroid-resistant colony from Tapachula, Mexico. We identified single-nucleotide polymorphisms (SNPs) associated with each phenotype and identified genes that are likely associated with the mechanisms of pyrethroid resistance, including detoxification, the cuticle, and insecticide target sites. We identified high association between kdr and mutations at VGSC and moderate association with additional insecticide target site, detoxification, and cuticle protein coding genes. Recovery was associated with cuticle proteins, the voltage-dependent calcium channel, and a different group of detoxification genes. We provide a list of detoxification genes under directional selection in this field-resistant population. Their functional roles in pyrethroid metabolism and their potential uses as genomic markers of resistance require validation.
| S-EPMC8211209 | biostudies-literature
Project description:Recent outbreaks of locally transmitted dengue and Zika viruses in Florida have placed more emphasis on integrated vector management plans for Aedes aegypti (L.) and Aedes albopictus Skuse. Adulticiding, primarily with pyrethroids, is often employed for the immediate control of potentially arbovirus-infected mosquitoes during outbreak situations. While pyrethroid resistance is common in Ae. aegypti worldwide and testing is recommended by CDC and WHO, resistance to this class of products has not been widely examined or quantified in Florida. To address this information gap, we performed the first study to quantify both pyrethroid resistance and genetic markers of pyrethroid resistance in Ae. aegypti and Ae. albopictus strains in Florida. Using direct topical application to measure intrinsic toxicity, we examined 21 Ae. aegypti strains from 9 counties and found permethrin resistance (resistance ratio (RR) = 6-61-fold) in all strains when compared to the susceptible ORL1952 control strain. Permethrin resistance in five strains of Ae. albopictus was very low (RR<1.6) even when collected from the same containers producing resistant Ae. aegypti. Characterization of two sodium channel kdr alleles associated with pyrethroid-resistance showed widespread distribution in 62 strains of Ae. aegypti. The 1534 phenylalanine to cysteine (F1534C) single nucleotide polymorphism SNP was fixed or nearly fixed in all strains regardless of RR. We observed much more variation in the 1016 valine to isoleucine (V1016I) allele and observed that an increasing frequency of the homozygous V1016I allele correlates strongly with increased RR (Pearson corr = 0.905). In agreement with previous studies, we observed a very low frequency of three kdr genotypes, IIFF, VIFF, and IIFC. In this study, we provide a statewide examination of pyrethroid resistance, and demonstrate that permethrin resistance and the genetic markers for resistance are widely present in FL Ae. aegypti. Resistance testing should be included in an effective management program.
| S-EPMC6218098 | biostudies-literature
Project description:BackgroundThe integration of house-screening and long-lasting insecticidal nets, known as insecticide-treated screening (ITS), can provide simple, safe, and low-tech Aedes aegypti control. Cluster randomised controlled trials in two endemic localities for Ae. aegypti of south Mexico, showed that ITS conferred both, immediate and sustained (~2 yr) impact on indoor-female Ae. aegypti infestations. Such encouraging results require further validation with studies quantifying more epidemiologically-related endpoints, including arbovirus infection in Ae. aegypti. We evaluated the efficacy of protecting houses with ITS on Ae. aegypti infestation and arbovirus infection during a Zika outbreak in Merida, Yucatan, Mexico.Methodology/principal findingsA two-arm cluster-randomised controlled trial evaluated the entomological efficacy of ITS compared to the absence of ITS (with both arms able to receive routine arbovirus vector control) in the neighbourhood Juan Pablo II of Merida. Cross-sectional entomological surveys quantified indoor adult mosquito infestation and arbovirus infection at baseline (pre-ITS installation) and throughout two post-intervention (PI) surveys spaced at 6-month intervals corresponding to dry/rainy seasons over one year (2016-2017). Household-surveys assessed the social reception of the intervention. Houses with ITS were 79-85% less infested with Aedes females than control houses up to one-year PI. A similar significant trend was observed for blood-fed Ae. aegypti females (76-82%). Houses with ITS had significantly less infected female Ae. aegypti than controls during the peak of the epidemic (OR = 0.15, 95%CI: 0.08-0.29), an effect that was significant up to a year PI (OR = 0.24, 0.15-0.39). Communities strongly accepted the intervention, due to its perceived mode of action, the prevalent risk for Aedes-borne diseases in the area, and the positive feedback from neighbours receiving ITS.Conclusions/significanceWe show evidence of the protective efficacy of ITS against an arboviral disease of major relevance, and discuss the relevance of our findings for intervention adoption.
| S-EPMC7853519 | biostudies-literature
Project description:Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti, which is also the vector of dengue virus; however, little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole A. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days postinfection using transcriptome sequencing. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic processes, cellular processes, and proteolysis. In addition, 486 long intergenic noncoding RNAs that were altered upon ZIKV infection were identified. Further, we found changes of a number of potential mRNA target genes correlating with those of altered host microRNAs. The outcomes provide a basic understanding of A. aegypti responses to ZIKV and help to determine host factors involved in replication or mosquito host antiviral response against the virus. IMPORTANCE Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including dengue virus, which is transmitted by the same mosquito vector. The outcomes provide a global picture of changes in the mosquito vector in response to Zika virus infection.
| S-EPMC5700376 | biostudies-literature
Project description:Saliva of Aedes aegypti contains a complex array of proteins essential for both blood feeding and pathogen transmission. A large numbers of those proteins are classified as unknown in regard to their function(s). Understanding the dynamic interactions at the mosquito-host interface can be achieved in part by characterizing mosquito salivary gland gene expression relative to blood feeding. Towards this end, we developed an oligonucleotide microarray representing 463 transcripts to determine differential regulation of salivary gland genes. This microarray was used to investigate the temporal gene expression pattern of Ae. aegypti salivary gland transcriptome at different times post-blood feeding. Expression of the majority of salivary gland genes (77-87%) did not change significantly as a result of blood feeding, while 8 to 20% of genes were down-regulated and 2.8 to 11.6% genes were up-regulated. Up-regulated genes included defensins, mucins and other immune related proteins. Odorant-binding protein was significantly down-regulated. Among unknown function proteins, several were up-regulated during the first three hours post-blood feeding and one was significantly down-regulated. Quantitative real-time RT-PCR was used to substantiate differential expression patterns of five randomly selected genes. Linear regression analysis revealed a high degree of correlation (R2 > 0.89) between oligonucleotide microarray and quantitative RT-PCR data. To our knowledge, this is the first study to investigate differential expression of the Ae. aegypti salivary gland transcriptome upon blood feeding. A microarray provides a robust, sensitive way to investigate differential regulation of mosquito salivary gland genes.
| S-EPMC2720950 | biostudies-literature
Project description:This study is intended to provide a comprehensive characterization of the resistance mechanisms in the permethrin-selected (IMR-PSS) and laboratory susceptible (IMR-LS) Aedes aegypti strain from Malaysia. Both IMR-PSS and IMR-LS provide a standard model for use in assessing the pyrethroid resistance in field-collected strains collected from three dengue hotspots: the Taman Seri Bayu (TSB), the Flat Camar (FC), and the Taman Dahlia (TD). Two established methods for determining the resistance mechanisms of the pyrethroid are the quantification of detoxification enzymes via enzyme microassay and the nucleotide sequencing of the domain 2 region from segment 1 to 6 via classical polymerase chain reaction (PCR) amplification-were employed. Enzyme activities in IMR-LS served as the resistance threshold reference, providing a significant standard for comparison with IMR-PSS and other field-collected strains. The amino acids in the domain 2 region of voltage-gated sodium channel (Vgsc) of IMR-LS were served as the reference for detection of any changes of the knockdown resistance (kdr) alleles in IMR-PSS and field-collected strains. Studies clearly indicated that the IMR-LS was highly susceptible to insecticides, whilst the IMR-PSS was highly resistant to pyrethroids and conferred with two resistance mechanisms: the elevated oxidase enzyme activity and the altered target-site mutations. Mutations of V1023G alone, and the combination mutations of V1023G with S996P in IMR-PSS, as well as the in field-collected Aedes aegypti strain, indicate the spread of the (kdr) gene in Aedes aegypti, particularly in dengue-endemic areas in Malaysia.
| S-EPMC6023340 | biostudies-literature