Targeting bacterial outer-membrane remodelling to impact antimicrobial drug resistance

The cell envelope is essential for survival and adaptation of bacteria. Bacterial membrane proteins include the major porins that mediate the influx of nutrients and several classes of antimicrobial drugs. Consequently, membrane remodelling is closely linked to antimicrobial resistance (AMR). Knowledge of bacterial membrane protein biogenesis and turnover underpins our understanding of bacterial membrane remodelling and the consequences that this process have in the evolution of AMR phenotypes. At the population level, the evolution of phenotypes is a reversible process, and we can use these insights to deploy evolutionary principles to resensitize bacteria to existing antimicrobial drugs. In our opinion, fundamental knowledge is opening a new way of thinking towards sustainable solutions to the mounting crisis in AMR. Here we discuss what is known about outer-membrane remodelling in bacteria and how the process could be targeted as a means to restore sensitivity to antimicrobial drugs. Bacteriophages are highlighted as a powerful means to exert this control over membrane remodelling but they require careful selection so as to reverse, and not exacerbate, AMR phenotypes.

Automated summary

The cell envelope of bacteria is essential for their survival and adaptation. The process of membrane remodelling is closely linked to antimicrobial resistance (AMR). Understanding the biogenesis and turnover of bacterial membrane proteins is crucial in comprehending bacterial membrane remodelling and its role in the evolution of AMR phenotypes. This fundamental knowledge provides a new perspective for sustainable solutions in combating the AMR crisis.