Kasugamycin and Validamycin differentially inhibit housefly larval growth through gut microbiota regulation

Certain bactericides exhibit dual efficacy in suppressing phytopathogens and managing insect pests. The houseflies may ingest organic matter containing bactericide residues, thereby facilitate the bioaccumulation of toxic compounds within ecosystems through trophic transfer mechanisms. Although it is known that gut microbiota regulates insect growth, immunity, and xenobiotic resistance, their responses to bactericide exposure are not well understood. This study examined the toxicological effects of two microbial-derived bactericides, Kasugamycin and Validamycin, on houseflies, along with their regulatory impacts on both the intestinal microbiota of housefly larvae and environmental microorganisms. Our research revealed that Validamycin exposure exhibited no significant effects on larval growth parameters, immune competence, or gut microbial composition. In contrast, Kasugamycin administration markedly inhibited larval development, compromised immunological defenses, and provoked histopathology modifications including fat body depletion and cuticle thinning. Microbiome analysis revealed Kasugamycin-induced dysbiosis characterized by a decrease in Klebsiella and Enterobacter, alongside an increase in Pseudomonas and Bordetella. Based on the aforementioned results, the influence of specific microbial communities' abundance shifts in the living environment on Kasugamycin toxicity was systematically assessed. The results demonstrate that Enterobacter hormaechei and Klebsiella pneumoniae enhanced larval resistance to Kasugamycin toxicity, whereas phage-mediated depletion of Pseudomonas aeruginosa is beneficial for the survival of housefly larvae during Kasugamycin exposure. These findings establish that the differential regulation of gut microbiota underlies the distinct effects of Kasugamycin and Validamycin on dipteran pests, providing mechanistic insights into antibiotic-insect-microbiome interactions and a theoretical framework for developing next-generation antimicrobial pest management strategies.