Anaerobiosis modulates the performance of antimicrobial resistance genes inEnterobacterales

Abstract

AbstractBacteria 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.Enterobacteralescomprise 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 inEnterobacteralescan be influenced by oxygen pressure. To do so, we have compared the MIC in aerobic and anaerobic conditions of isogenicEscherichia colistrains 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 amongblaVIMß-lactamases andfosgenes respectively. The pattern of resistance change in anaerobiosis was also conserved inKlebsiella 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.ImportanceAntibiotic chemotherapy is often based on the results of antibiograms performed in aerobic conditions. Yet many body compartments and infection sites are anaerobic. Enterobacteria are among the deadliest and most antibiotic-resistant pathogens worldwide. They are also commensal inhabitants of our gut, where they thrive in the absence of oxygen. This work shows that antimicrobial resistance genes in enterobacteria can confer different resistance levels in aerobic/anaerobic conditions. Such effect can be important when treating anaerobic infection sites based on antibiogram results. On one hand, the selected therapy can fail in the case of genes that confer higher resistance in anaerobiosis, likeblaOXA-48; on the other, successful therapeutic options might be wrongly discarded if the gene confers lower levels of resistance in anaerobiosis, likeblaVIMcarbapenemases. Our results indicate that anaerobic conditions of the site of infection can be an important aspect to consider when treating antimicrobial-resistant bacteria.