Role of hydrogen sulfide in bacterial antibiotic tolerance: from mechanisms to therapeutic targeting

Abstract

Hydrogen sulfide (H 2 S) is fundamentally a gaseous signaling molecule in bacteria. Recent studies have reported that H 2 S is a key mediator of bacterial antibiotic tolerance, making it a promising strategic target for overcoming tolerance, eliminating persisters, and restoring antibiotic efficacy. We systematically review recent advances in H 2 S-mediated multidrug tolerance mechanisms, highlighting three core pathways: iron chelation for antioxidant defense, reactive sulfur species-mediated antibiotic inactivation and efflux pump activation, and metabolic dormancy induced by respiratory inhibition, and note that recent advances in H 2 S fluorescent probes have provided important tools for monitoring intracellular H 2 S changes in bacteria under antibiotic stress. Furthermore, this review systematically summarizes recent advances in the development of novel inhibitors targeting intracellular H 2 S biosynthesis in bacteria.