Anaerobiosis modulates the performance of antimicrobial resistance genes in Enterobacterales

Bacteria must face and adapt to a variety of physicochemical conditions in the environment and during infection. A key condition is the partial pressure of oxygen (PO2), since many colonizable compartments are anaerobic. Enterobacterales comprise frequently resistant pathogens with complex and diverse lifestyles, capable of thriving in the (anaerobic) gut, and the environment. Here, we sought to understand if resistance determinants commonly found in Enterobacterales can be influenced by oxygen pressure. To do so, we have compared the MIC in aerobic and anaerobic conditions of isogenic Escherichia coli strains containing 136 different resistance genes against 9 antibiotic families. Our results show a complex landscape of changes in the performance of resistance genes in anaerobiosis. Certain changes are especially relevant for their intensity and the importance of the antibiotic family, like the large decreases in resistance observed against ertapenem and fosfomycin among bla VIM β-lactamases and fos genes respectively. The pattern of resistance change in anaerobiosis was also conserved in Klebsiella pneumoniae -although with different intensity. Analyzing other genetic elements of clinical relevance, we observed that pOXA-48 plasmid conferred 4-fold higher ertapenem resistance in anaerobiosis. Last, using a collection of clinical isolates and agar diffusion susceptibility tests, we show that antibiotic susceptibility of multidrug resistant strains differs between aerobic/anaerobic conditions. Our results suggest that anaerobiosis is a relevant aspect that can affect antimicrobial activity in the clinical setting, as well as in the understanding of the local selection and spread of some AMR genes. ### Competing Interest Statement The authors have declared no competing interest.