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

BACKGROUND: Anopheles 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. METHODS: Juvenile 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. RESULTS: Expressions 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. CONCLUSION: These 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.

Cadmium tolerance pathway in Anopheles gambiae senso stricto.

Cadmium is one of the widely used heavy metals (HM) in commercial and industrial products and contributes to environmental contamination in an urban setting. In our previous studies, we established that An. gambiae sensu stricto, a vector of malaria, had adapted to HM pollutants in nature despite their proclivity for unpolluted aquatic habitats. We further demonstrated that heavy metal tolerance adaptation process impacts a biological cost to the fitness of the mosquito and potentially involves the induction of specific HM-responsive transcripts and proteins. Here we interrogated differential proteomic profiles of the cadmium tolerant vs. naïve strains of An. gambiae to shed light on proteomic processes that underpinned biological cost to fitness. We identified a total of 1067 larval proteins and observed significant down-regulation of proteins involved in larval immune responses, energy metabolism, antioxidant enzymes, protein synthesis, and proton transport. Our results suggest that mosquitoes can adjust their biological program through proteome changes to counter HM pollution. Since our study was done in controlled laboratory settings, we acknowledge this may not wholly represent the conditions HM polluted environments. Nevertheless, mosquitoes deploying this strategy have the potential of creating an urban enclave for breeding and thrive and become agents of sporadic malaria epidemics.