Dataset Information

Molecular basis of resistance to organophosphate insecticides in the New World screw-worm fly.

ABSTRACT: BACKGROUND:The emergence of insecticide resistance is a fast-paced example of the evolutionary process of natural selection. In this study, we investigated the molecular basis of resistance in the myiasis-causing fly Cochliomyia hominivorax (Diptera: Calliphoridae) to dimethyl-organophosphate (OP) insecticides. METHODS:By sequencing the RNA from surviving larvae treated with dimethyl-OP (resistant condition) and non-treated larvae (control condition), we identified genes displaying condition-specific polymorphisms, as well as those differentially expressed. RESULTS:Both analyses revealed that resistant individuals have altered expression and allele-specific expression of genes involved in proteolysis (specifically serine-endopeptidase), olfactory perception and cuticle metabolism, among others. We also confirmed that resistant individuals carry almost invariably the Trp251Ser mutation in the esterase E3, known to confer OP and Pyrethroid resistance. Interestingly, genes involved in metabolic and detoxifying processes (notably cytochrome P450s) were found under-expressed in resistant individuals. An exception to this were esterases, which were found up-regulated. CONCLUSIONS:These observations suggest that reduced penetration and aversion to dimethyl-OP contaminated food may be important complementary strategies of resistant individuals. The specific genes and processes found are an important starting point for future functional studies. Their role in insecticide resistance merits consideration to better the current pest management strategies.

SUBMITTER: Tandonnet S

PROVIDER: S-EPMC7653728 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Molecular basis of resistance to organophosphate insecticides in the New World screw-worm fly.

Tandonnet Sophie S Cardoso Gisele Antoniazzi GA Mariano-Martins Pedro P Monfardini Raquel Dietsche RD Cunha Vanessa A S VAS de Carvalho Renato Assis RA Torres Tatiana Teixeira TT

Parasites & vectors 20201110 1

<h4>Background</h4>The emergence of insecticide resistance is a fast-paced example of the evolutionary process of natural selection. In this study, we investigated the molecular basis of resistance in the myiasis-causing fly Cochliomyia hominivorax (Diptera: Calliphoridae) to dimethyl-organophosphate (OP) insecticides.<h4>Methods</h4>By sequencing the RNA from surviving larvae treated with dimethyl-OP (resistant condition) and non-treated larvae (control condition), we identified genes displayin ...[more]

PMID: 33168079

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Project description:BACKGROUND: The New World screw-worm (NWS), Cochliomyia hominivorax, is one of the most important myiasis-causing flies, causing severe losses to the livestock industry. In its current geographical distribution, this species has been controlled by the application of insecticides, mainly organophosphate (OP) compounds, but a number of lineages have been identified that are resistant to such chemicals. Despite its economic importance, only limited genetic information is available for the NWS. Here, as a part of an effort to characterize the C. hominivorax genome and identify putative genes involved in insecticide resistance, we sampled its transcriptome by deep sequencing of polyadenylated transcripts using the 454 sequencing technology. RESULTS: Deep sequencing on the 454 platform of three normalized libraries (larval, adult male and adult female) generated a total of 548,940 reads. Eighteen candidate genes coding for three metabolic detoxification enzyme families, cytochrome P450 monooxygenases, glutathione S-transferases and carboxyl/cholinesterases were selected and gene expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Of the investigated candidates, only one gene was expressed differently between control and resistant larvae with, at least, a 10-fold down-regulation in the resistant larvae. The presence of mutations in the acetylcholinesterase (target site) and carboxylesterase E3 genes was investigated and all of the resistant flies presented E3 mutations previously associated with insecticide resistance. CONCLUSIONS: Here, we provided the largest database of NWS expressed sequence tags that is an important resource, not only for further studies on the molecular basis of the OP resistance in NWS fly, but also for functional and comparative studies among Calliphoridae flies. Among our candidates, only one gene was found differentially expressed in resistant individuals, and its role on insecticide resistance should be further investigated. Furthermore, the absence of mutations in the OP target site and the high frequency of mutant carboxylesterase E3 indicate that metabolic resistance mechanisms have evolved predominantly in this species.

Project description:BackgroundOrganophosphate (OP) insecticides represent one of the largest classes of sprayed insecticides in the U.S., and their use has been associated with various adverse health outcomes, including disorders of blood pressure regulation such as hypertension (HTN).MethodsIn a study of 935 adults from the NHANES 2013-2014 cycle, we examined the relationship between systolic and diastolic blood pressure changes and urinary concentrations of three OP insecticides metabolites, including 3,5,6-trichloro-2-pyridinol (TCPy), oxypyrimidine, and para-nitrophenol. These metabolites correspond to the parent compounds chlorpyrifos, diazinon, and methyl parathion, respectively. Weighted, multivariable linear regression analysis while adjusting for potential confounders were used to model the relationship between OP metabolites and blood pressure. Weighted, multivariable logistic regression analysis was used to model the odds of HTN for quartile of metabolites.ResultsWe observed significant, inverse association between TCPy on systolic blood pressure (β-estimate = -0.16, p < 0.001) and diastolic blood pressure (β-estimate = -0.15, p < 0.001). Analysis with para-nitrophenol revealed a significant, positive association with systolic blood pressure (β-estimate = 0.03, p = 0.02), and an inverse association with diastolic blood pressure (β-estimate = -0.09, p < 0.001). For oxypyrimidine, we observed significant, positive associations between systolic blood pressure (β-estimate = 0.58, p = 0.03) and diastolic blood pressure (β-estimate = 0.31, p < 0.001). Furthermore, we observed significant interactions between TCPy and ethnicity on systolic blood pressure (β-estimate = 1.46, p = 0.0036). Significant interaction terms were observed between oxypyrimidine and ethnicity (β-estimate = -1.73, p < 0.001), as well as oxypyrimidine and BMI (β-estimate = 1.51 p < 0.001) on systolic blood pressure, and between oxypyrimidine and age (β-estimate = 1.96, p = 0.02), race (β-estimate = -3.81 p = 0.004), and BMI on diastolic blood pressure (β-estimate = 0.72, p = 0.02). A significant interaction was observed between para-nitrophenol and BMI for systolic blood pressure (β-estimate = 0.43, p = 0.01), and between para-nitrophenol and ethnicity on diastolic blood pressure (β-estimate = 2.19, p = 0.006). Lastly, we observed a significant association between the odds of HTN and TCPy quartiles (OR = 0.65, 95% CI [0.43,0.99]).ConclusionOur findings support previous studies suggesting a role for organophosphate insecticides in the etiology of blood pressure dysregulation and HTN. Future studies are warranted to corroborate these findings, evaluate dose-response relationships between organophosphate insecticides and blood pressure, determine clinical significance, and elucidate biological mechanisms underlying this association.

Project description:Endometriosis is a hormone-responsive gynecologic disease, signifying its connotations across a woman's life span. Previous studies suggested that endocrine disrupting chemicals were risk factors for endometriosis. Nevertheless, little is known on exposure to organophosphate, pyrethroid and phenoxy acid pesticides on endometriosis diagnosis. In this study, we determined the concentrations of 11 pesticides, metabolites of organophosphate and pyrethroid insecticides, and phenoxy herbicides, in urine collected from 619 reproductive-age women in Utah and California, using liquid chromatography-tandem mass spectrometry. The association of urinary concentrations of pesticides with an increase in the odds of endometriosis diagnosis was examined in 594 women who underwent laparoscopy/laparotomy (operative cohort: n = 471) or pelvic magnetic resonance imaging (population cohort: n = 123), during 2007-2009. 2-Isopropyl-4-methyl-6-hydroxypyrimidine (IMPY), malathion dicarboxylic acid (MDA), para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TCPY), 3-phenoxybenzoic acid (3-PBA), and 2,4-dichlorophenoxyacetic acid (2,4-D) were detected in ≥95% of the urine samples analyzed. Urinary concentrations of IMPY, MDA, PNP, 3-PBA and 2,4-D tended to be higher in younger, non-Hispanic black, nulliparous and less affluent women. IMPY was the most dominant compound in urine followed by PNP and TCPY. When women in the 4th quartile of IMPY and the 2nd quartile of TCPY concentrations (μg/g creatinine) were compared with women in the 1st quartile, the odds ratios (ORs) for diagnosis of endometriosis increased significantly in unadjusted models (IMPY OR = 1.89, 95% confidence interval (Cl) = 1.12-3.20; TCPY OR = 1.65, 95% Cl = 1.02-2.69) for the operative (n = 471) and entire data set (n = 594), respectively. Our results suggest that exposure to elevated concentrations of diazinon (the parent compound of IMPY) and chlorpyrifos and chlorpyrifos-methyl (parent compounds of TCPY) may be associated with endometriosis.

Dataset Information

Molecular basis of resistance to organophosphate insecticides in the New World screw-worm fly.

Publications

Molecular basis of resistance to organophosphate insecticides in the New World screw-worm fly.

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