Abstract
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.
Highlights
The cell envelope is essential for survival and adaptation of bacteria
1Centre to Impact antimicrobial resistance (AMR), Monash University, Melbourne, Australia 2Infection and Immunity Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Australia. In this opinion piece we explore the relationships between bacterial membrane remodelling and AMR
The gene-regulatory mechanisms that control membrane remodelling are worthy of further investigation since, for example, factors that can switch on porin expression would be a valuable means of restoring carbapenem sensitivity in an infection site
Summary
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. 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. We have knowledge of the signals that dictate which porin-encoding genes are activated under specific environmental stimuli, including the presence of antimicrobial drugs These signals change the protein-specific composition of the outer membrane, a process referred to as outer-membrane remodelling. The general mechanisms by which mutations and/or adaptations confer AMR phenotypes on bacteria are known One of these mechanisms is outermembrane remodelling. Membrane remodelling to prevent drug influx at the cell surface, thereby protecting the internal compartments where most drug targets reside In this opinion piece we explore the relationships between bacterial membrane remodelling and AMR.
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