A “sensory appendage protein” protects malaria vectors from pyrethroids ??

The wide distribution of insecticide-treated mosquito nets — over the past two decades, across malaria-endemic regions — has markely decreased the incidence of malaria, saving probably millions of lives. Recently, however, malaria-carrying mosquitoes have now been found to have developed strong resistance to the pyrethroid chemicals used in these insecticidal nets. An understanding of the mechanisms underlying this recently developed “resistance” — would benefit society by making mosquitoes once again more susceptible. This topic is a classic “gene-environment interactions” and “evolution by adaptation” story 😊 : the environmental “signal” is the insecticide-treated net, which is causing difficulty for these mosquitoes to survive; hence, genes in their genome have been modified so as to “overcome” this adversity and once again allow the poor mosquito to survive. ☹

Authors [see attached article and editorial] discovered a surprising means by which mosquitoes in Africa neutralize pyrethroids: the insects use a class of small proteins normally involved in chemical communication, to improve the mosquito’s chances of survival. This intense selection pressure — exerted by pyrethroid-impregnated bed nets — has triggered widespread and escalating resistance to pyrethroids in Anopheles populations; and this adaptation (by the mosquito’s genome) to this environmental adversity now threatens to reverse the gains that been made by malaria control. Authors show that expression of sensory appendage protein-2 (SAP2), enriched in mosquito’s legs, is involved in pyrethroid resistance in Anopheles gambiae. SAP2-gene expression was found to be increased in insecticide-resistant populations and to become further induced — if the insect comes into contact with pyrethroids. SAP2-gene silencing fully restored pyrethroid sensitivity (and mortality of the mosquitoes) — whereas SAP2-gene over-expression resulted in increased resistance — probably owing to high-affinity binding of SAP2 to pyrethroid insecticides.

Anopheles mosquitoes are the only genus capable of transmitting human malaria. Contact with pyrethroid insecticide also decreases the likelihood that mosquitoes will survive long enough to develop and transmit the Plasmodium parasite (which causes malaria in warm-blooded hosts). Pyrethroid nets contain the synergist piperonyl butoxide (PBO), a potent inhibitor of metabolic resistance mediated by cytochromes P450s — one of the most widespread, and hitherto most potent, resistance mechanisms. Blocking this resistance mechanism allows these PBO–pyrethroid nets to produce insecticide susceptibility, leading to a reduction in malaria cases in areas in which metabolic resistance had prevailed.

Data-mining of the mosquito genome reveals a “selective sweep” near the SAP2 locus in mosquito populations of three West African countries (Cameroon, Guinea and Burkina Faso), concomitant with the reported increased frequency in haplotype-associated single-nucleotide variants (SNVs) — this finding is consistent with previous reports of increasing resistance of mosquitoes in Burkina Faso (recall that ‘haplotype’ represents a group of genes inherited together on one chromosome of the chromosome pair, i.e. originating from one of the two parents). This study therefore identifies a previously undescribed mechanism of insecticide resistance that is likely to be highly relevant to future malaria-control efforts.


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