Environmental factors modulate β-lactamase phenotypes: effect of pH and redox potential on β-lactam resistance

Environmental factors may have unnoticed effects on the activity of β-lactamases against β-lactams. We constructed a panel of Escherichia coli strains expressing 16 different β-lactamases and determined the MICs of 10 β-lactams under aerobic conditions at different pH values and under anaerobic conditions. We observed a contrasting effect of pH on MICs depending on the β-lactam and β-lactamase. Anaerobiosis generally increased MICs, but the effect depended completely on the exact gene and β-lactam.IMPORTANCEHuge efforts have gone into standardization of antimicrobial susceptibility testing. However, bacteria do not live under standardized conditions and the possible importance of constantly changing environmental conditions on the efficacy of antibiotics and resistance genes might have been overlooked. Here we assess the influence of media pH and anaerobiosis on the resistance (MIC) of 16 widespread and critical β-lactamases. We observed a contrasting effect of pH on MICs depending on the β-lactam and β-lactamase, while anaerobiosis generally increased MICs, but with effects depending on the exact gene and beta-lactam. This can have major importance for our understanding of interpretation of standardized in vitro MIC results for treatment, as well as ecology and evolution of AMR.