Exposure of gut bacterial isolates to the anthelminthic drugs, ivermectin and moxidectin, leads to antibiotic-like phenotypes of growth inhibition and adaptation

Due to their broad-spectrum activities, ivermectin and moxidectin are widely used anthelminthics in veterinary and human medicine. However, ivermectin has recently been shown to perturbate bacterial growth. Given the macrolide-like structure of both ivermectin and moxidectin, there is a need to characterize the antibiotic spectrum of these anthelminthics and their potential implications in the development of cross-resistance to macrolides and other families of antibiotics. Here, we characterize growth dynamics of 59 bacterial isolates in presence of ivermectin and moxidectin. Further, we assessed the effect of repeated anthelminthic exposure in 5 bacterial isolates on sensitivity to different antibiotics, both via growth dynamics and minimal inhibitory concentration. We found, that anthelminthic growth phenotypes are comparable to a selection of tested antibiotics. Bacterial anthelminthic challenging resulted in decreased anthelminthic sensitivity, and to some extent, decreased antibiotic sensitivity. Hence, potential off-target effects of large-scale administration of ivermectin and moxidectin should be carefully monitored.