The ionophore resistance genes <i>narA</i> and <i>narB</i> are geographically widespread and linked to resistance to medically important antibiotics

Ionophores are a class of antibiotics used widely in animal production as anti-coccidials and for growth promotion. Since ionophores are not used in human medicine, it has largely been assumed that they do not contribute to medically important antimicrobial resistance (AMR). Nonetheless, there is increasing concern that ionophore usage could co-select for clinically relevant AMR, since the ionophore resistance genes <i>narA</i> and <i>narB</i> have been found in linkage with multiple AMR genes. We investigated the global distribution and AMR linkage of <i>narA</i> and <i>narB</i> using publicly available data. These ionophore resistance genes can be found worldwide, with >2,400 <i>narAB</i>-bearing isolates reported from 51 countries. Isolates were derived from a range of host species, including poultry, cattle, and humans. <i>narAB</i> was linked with an average of over 10 resistance determinants for AMR, including many medically important antibiotics. These observations indicate that we cannot assume that ionophore use is risk-free, with clear potential for co-selection for clinically relevant AMR.IMPORTANCEIonophores are a type of antibiotic used to promote growth in cattle and pigs and to treat parasitic infections in poultry. It has been assumed that ionophore use in animals does not pose a risk for humans. However, growing evidence suggests that ionophore use may select for medically relevant antibiotic resistance. Using analyses of public data, we found that ionophore resistance is widespread and that it is usually linked to resistance genes for medically relevant drugs. There is thus clear potential for ionophore use to impact the presence of antibiotic resistance genes in the food supply.