Bacterial metabolism-inspired molecules to modulate antibiotic efficacy.

The decreasing antibiotic susceptibility of bacterial pathogens calls for novel antimicrobial therapies. Traditional screening pathways based on drug-target interaction have gradually reached the stage of diminishing returns. Thus, novel strategies are urgently needed in the fight against antibiotic-refractory bacteria, particularly for tolerant bacteria. Recently, evidence has accumulated demonstrating that microbial changes caused by bacterial metabolic processes significantly modulate antibiotic killing. A better understanding of these bacterial metabolic processes is indicating a need to screen novel metabolic modulators as potential antibiotic adjuvants. In this review, we describe the state of our current knowledge about how these bacterial metabolism-inspired molecules affect antibiotic efficacy, including potentiation and inhibition activity. In addition, the challenges faced and prospects for bringing them into clinic are also discussed. These examples may provide candidates or targets for the development of novel antibiotic adjuvants.