Anopheles resistance to deltamethrin can be caused by the increased abundance of an enteric Aeromonas taxon

The enteric bacteriome of Anopheles mosquito vector has been linked with its vectorial competence, however, its influence on insecticide resistance is poorly understood. We found that the depletion of the bacterial microbiome in susceptible Anopheles strains, resulting from antibiotic treatment, led to greater than 50% insecticide deltamethrin tolerance compared to untreated mosquitoes. Simultaneous inhibition of cytochrome P450 activity reverted the antibiotic-induced tolerance phenotype, indicating that the antibiotic-induced deltamethrin tolerance is P450-dependent. We found that the antibiotic treatment, while suppressing most enteric bacterial taxa, allowed proliferation of a particular antibiotic-tolerant Aeromonas taxon, most closely related to Aeromonas hydrophila. Increasing the abundance of this taxon in mosquitoes not treated with antibiotics phenocopied the tolerance phenotype, converting deltamethrin-susceptible Anopheles to deltamethrin-tolerant mosquitoes. Collectively, these results highlight a mechanistic interplay in Anopheles mosquitoes between antibiotic-induced enteric dysbiosis and cytochrome P450-mediated detoxification that promotes insecticide tolerance. This effect could influence mosquito vectorial capacity, especially in Africa, where auto-medication with antibiotics is highly prevalent.