Bacterial metabolism and susceptibility to cell wall-active antibiotics

Bacterial infections are increasingly resistant to antimicrobial therapy. Intense research focus has thus been placed on identifying the mechanisms that bacteria use to resist killing or growth inhibition by antibiotics and the ways in which bacteria share these traits with one another. This work has led to the advancement of new drugs, combination therapy regimens, and a deeper appreciation for the adaptability seen in microorganisms. However, while the primary mechanisms of action of most antibiotics are well understood, the more subtle contributions of bacterial metabolic state to repairing or preventing damage caused by antimicrobials (thereby promoting survival) are still understudied. Here, we review a modern viewpoint on a classical system: examining bacterial metabolism's connection to antibiotic susceptibility. We dive into the relationship between metabolism and antibiotic efficacy through the lens of growth rate, energy state, resource allocation, and the infection environment, focusing on cell wall-active antibiotics.