Symbiotic Stenotrophomonas maltophilia is associated with ivermectin resistance in the parasitic nematode Haemonchus contortus via metabolic detoxification

Abstract

Anthelmintic resistance constitutes a global threat to the control of parasitic nematodes. Current research has primarily focused on parasite-intrinsic genetic mechanisms, while the contribution of the symbiotic microbial community remains a key knowledge gap. Here, we report that ivermectin (IVM) resistance in the gastrointestinal nematode Haemonchus contortus is associated with the abundance of the bacterium Stenotrophomonas maltophilia. A representative strain, designated SM1, was isolated from resistant populations, and its abundance was associated with the resistant phenotype. Depletion of SM1 increased larval susceptibility to IVM, whereas reintroduction of the bacterium partially enhanced IVM tolerance. Metabolic analysis indicated that SM1 converts IVM into demethylated and oxo-derivatives (M1, M4, and M7). Using in silico analysis, the putative cytochrome P450 monooxygenase (Cmp08160) with a possible participation in IVM biotransformation was identified. Collectively, these findings suggest that symbiotic bacteria can influence IVM susceptibility in H. contortus and highlight the relevance of considering host–microbiota interactions in studies of anthelmintic resistance.