Metabolic Adaptation and Antibiotic Resistance in Bacterial Pathogens

Abstract

Antibiotic resistance is a major worldwide health problem that compromises our ability to treat bacterial diseases. Antibiotic resistance is often ascribed to genetic mechanisms like antibiotic-inactivating enzymes, target modification and drug efflux, but there is growing evidence that bacterial metabolic adaptation also impacts antibiotic susceptibility, tolerance, persistence and the evolution of resistance. Metabolic activities are responsible for energy production, redox balance, membrane transport, biosynthesis and stress responses, and hence dictate how bacteria react to antimicrobial exposure. Altered antibiotic activity and bacterial survival may be caused by changes in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, amino acid metabolism and carbon utilisation. In addition, metabolic variability within bacterial populations and biofilms can result in physiological situations where some cells survive antibiotic treatment without being heritably resistant. This review highlights the biochemical and molecular processes of the interaction between bacterial metabolism and antibiotic resistance with special emphasis on energy metabolism, redox balance, membrane transport, stress adaption and persistence. It also covers developing treatment approaches such as metabolic adjuvants, disruption of biofilm metabolism, targeting bacterial energy pathways and metabolomics-guided development of antimicrobials. Understanding the metabolic basis of antibiotic reactions may aid in the creation of more effective treatment options. However, the effects of metabolic treatments are different depending on bacterial species, infection environment, antibiotic class and host circumstances, which needs to be carefully evaluated.