Deltamethrin Resistance Mechanisms in Aedes aegypti Populations from Three French Overseas Territories Worldwide

Abstract

Background: Aedes aegypti is a cosmopolite mosquito, vector of arboviruses. The worldwide studies of its insecticide resistance have demonstrated a strong loss of susceptibility to pyrethroids, the major class of insecticide used for vector control. French overseas territories such as French Guiana (South America), Guadeloupe islands (Lesser Antilles) as well as New Caledonia (Pacific Ocean), have encountered such resistance.

Methodology/principal findings: We initiated a research program on the pyrethroid resistance in French Guiana, Guadeloupe and New Caledonia. Aedes aegypti populations were tested for their deltamethrin resistance level then screened by an improved microarray developed to specifically study metabolic resistance mechanisms. Cytochrome P450 genes were implicated in conferring resistance. CYP6BB2, CYP6M11, CYP6N12, CYP9J9, CYP9J10 and CCE3 genes were upregulated in the resistant populations and were common to other populations at a regional scale. The implication of these genes in resistance phenomenon is therefore strongly suggested. Other genes from detoxification pathways were also differentially regulated. Screening for target site mutations on the voltage-gated sodium channel gene demonstrated the presence of I1016 and C1534.

Conclusion /significance: This study highlighted the presence of a common set of differentially up-regulated detoxifying genes, mainly cytochrome P450 genes in all three populations. GUA and GUY populations shared a higher number of those genes compared to CAL. Two kdr mutations well known to be associated to pyrethroid resistance were also detected in those two populations but not in CAL. Different selective pressures and genetic backgrounds can explain such differences. These results are also compared with those obtained from other parts of the world and are discussed in the context of integrative research on vector competence.

Fig 1. Cumulative histogram of genotype proportions per population and phenotype (S: susceptible, R: resistant).

Number of individuals are also mentioned (N). Based on the description of Linss et al. [29], four alleles were obtained ‘1016V + 1534F’ called S, ‘1016V + 1534C’ (1534 kdr) called R1, ‘1016I + 1534 C’ referred to as R2 (1016 kdr+1534 kdr) and ‘1016I + 1534 F’ referred to as R3 (1016 kdr).

Fig 2. Fold changes of detoxification genes differentially expressed in pyrethroid resistant populations relative to the susceptible NO strain (Fold change>2; p<0.001).

CYP: cytochrome P450 genes, CCE: carboxy/cholinesterase genes, GST: glutathione S-transferase genes.

Fig 3. Fold changes of differentially expressed genes with a putative role in detoxification gene regulation or transformation of their products relative to the susceptible NO strain (Fold change>2; p<0.001).