Sex-specific induction of CYP6 cytochrome P450 genes in cadmium and lead tolerant Anopheles gambiae

Abstract

BackgroundAnopheles gambiae, one of the main Afro-tropical mosquito vector of malaria, has adapted to heavy metals in its natural habitat, and developed resistance to most conventional insecticides. Investigations were conducted to establish an association between tolerance to cadmium or lead-heavy metals, and expression of specific genes for cytochrome p450 enzymes associated with pyrethroid resistance in the mosquito.MethodsJuvenile aquatic stages of the mosquito were selected for tolerance to cadmiun or lead through chronic exposure of the stages to maximum acceptable toxicant concentrations (MATCs) of the metals. Using real-time quantitative polymerase chain reaction (qPCR), three replicates each of male or female cadmium or lead-tolerant individuals and relevant controls were separately screened for expression of CYP6M2, CYP6P3 and CYP6Z1 genes. The variance in expression levels of the genes amongst the treatments was compared by ANOVA statistical tool.ResultsExpressions of all the genes were significantly lower (P <0.05) in females than in males. Within gender, there 1.3 - 2.3 or 3.1-4.2-fold reduction in expression of the genes in cadmium or lead selected than respective control populations. Expression of all the classes of gene was elevated in cadmium selected female populations relative to their respective controls.ConclusionThese findings suggest that tolerance to cadmium or lead in the mosquito can influence response in cytochrome p450 genes associated with metabolism of pyrethroids in the mosquito in a sex-specific manner. This can, in turn, affect sensitivity of the mosquito to pyrethroids and other xenobiotics associated with these genes, with potential implications in mosquito vector control operations.

The effect of metal pollution on the life history and insecticide resistance phenotype of the major malaria vector Anopheles arabiensis (Diptera: Culicidae)

“…Metal tolerant An . gambiae females generally showed increased CYP6 expression, while males typically showed decreased CYP6M2, CYP6P3 and CYP6Z1 expression [ 23 ]. It is important to note that the data from this study was obtained from metal naïve populations as opposed to metal tolerant strains, in contrast to the Musasia et al .…”

“…It is important to note that the data from this study was obtained from metal naïve populations as opposed to metal tolerant strains, in contrast to the Musasia et al . [ 23 ] study. This study suggests that an interplay between the Phase I enzymes the β-esterases and the cytochrome P450 proteins may be the key mediators in increased insecticide tolerance in adults eclosed from larvae exposed to metal pollutants.…”

“…Several cytochrome P450 genes, particularly in the CYP6 class, have also been associated with metal tolerance. The induction of these genes is sex-specific and although the relevant genes are expressed at their lowest levels in females, the gene induction was female specific, with males incurring a significant reduction in the expression of CYP6M2, CYP6P3 and CYP6Z1 [ 23 ].…”

Second generation effects of larval metal pollutant exposure on reproduction, longevity and insecticide tolerance in the major malaria vector Anopheles arabiensis (Diptera: Culicidae)

“…Hatchlings (less than 24 h) of the SENN and SENN-DDT strains (n = 200) were reared in either clean water or water polluted with the maximum acceptable toxic concentration (MATC) of cadmium chloride (0.36 µg/l), copper nitrate (1.86 µg/l) or lead nitrate (4.39 µg/l) [23]. The MATC values were chosen as they are the highest concentration of these common pollutants legally allowed in the environment.…”

Genetic Diversity in Insect Metal Tolerance

“…Metal-responsive ABC transporter genes are present in insects ( Sooksa-Nguan et al, 2009 ; Hull et al, 2014 ) and, in D. melanogaster , increased gene expression is associated with tolerance to metal exposure ( Sooksa-Nguan et al, 2009 ). Cadmium and Pb tolerant A. gambiae mosquitoes have significant reduction in expression of the CYP6 family of cytochrome p450 genes, a gene family associated with resistance to pyrethroid pesticides ( Musasia et al, 2013 ), suggesting potential interactions between metal tolerance and pesticide sensitivity. Expression of the alpha-tubulin gene also responds to metal concentrations in both A. gambiae ( Mireji et al, 2010a ) and Chironomus tentans midges ( Mattingly et al, 2001 ).…”