Advances and strategies in discovery of new antibacterials for combating metabolically resting bacteria

Discovery of new antibacterial agents is crucial to counter the challenge of drug-resistant bacterial infections. In this review we discuss the issue of bacterial metabolic resting states, observed for a variety of pathogenic bacteria, which display low susceptibility for most antibacterials. We present examples of how bacterial metabolic states may be controlled, target pathways may be validated and screening on metabolically resting bacteria can be designed. A deeper understanding of bacterial metabolic states may provide valuable input for the design of efficient screening approaches in the discovery of new antibacterial agents.

► Metabolically resting bacteria often recalcitrant to antibiotic chemotherapy. ► Screening with resting bacteria new strategy for antibacterial discovery. ► Whole-cell or pathway-based screening systems appear promising. ► Bacterial metabolism may be shifted toward a more drug-sensitive state. ► Scrutinizing knowledge on existing drugs/pathways may assist in target validation.