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

The enteric bacteriome of Anopheles mosquito vectors has been linked with vectorial competence; however, its influence on insecticide resistance is poorly understood. We found that antibiotic treatment—administered either through sugar feeding (penicillin/streptomycin and gentamicin) or via a blood meal (amoxicillin)—which depleted the bacterial microbiome in susceptible Anopheles strains, 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 mosquitoes 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 antibiotic self-medication is highly prevalent. IMPORTANCE Our findings highlight an unexpected link between antibiotic use and the effectiveness of mosquito control strategies. It shows that disrupting the natural gut bacteria of malaria-carrying mosquitoes can make them significantly more tolerant to insecticides commonly used in public health programs. This occurs because antibiotic treatment alters the microbial balance, allowing certain antibiotic-resistant bacteria to thrive and enhance the mosquito’s internal detoxification systems. As a result, mosquitoes that would normally be killed can survive exposure. These findings are important because they suggest that widespread antibiotic use—especially in regions heavily affected by malaria—could unintentionally reduce the impact of insecticide-based interventions such as bed nets and indoor spraying. This adds a new layer of complexity to vector control efforts and highlights the need to consider microbial and environmental factors alongside traditional approaches. Understanding this interaction could help improve strategies to combat insecticide resistance and better control mosquito-borne diseases.