New Strategies to Kill Metabolically-Dormant Cells Directly Bypassing the Need for Active Cellular Processes

Antibiotic therapy failure is often caused by the presence of persister cells, which are metabolically-dormant bacteria capable of surviving exposure to antimicrobials. Under favorable conditions, persisters can resume growth leading to recurrent infections. Moreover, several studies have indicated that persisters may promote the evolution of antimicrobial resistance and facilitate the selection of specific resistant mutants; therefore, in light of the increasing numbers of multidrug-resistant infections worldwide, developing efficient strategies against dormant cells is of paramount importance. In this review, we present and discuss the efficacy of various agents whose antimicrobial activity is independent of the metabolic status of the bacteria as they target cell envelope structures. Since the biofilm-environment is favorable for the formation of dormant subpopulations, anti-persister strategies should also include agents that destroy the biofilm matrix or inhibit biofilm development. This article reviews examples of selected cell wall hydrolases, polysaccharide depolymerases and antimicrobial peptides. Their combination with standard antibiotics seems to be the most promising approach in combating persistent infections.