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

Hydrogen sulfide (H2S) is fundamentally a gaseous signaling molecule in bacteria. Recent studies have reported that H2S 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 H2S-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 H2S fluorescent probes have provided important tools for monitoring intracellular H2S changes in bacteria under antibiotic stress. Furthermore, this review systematically summarizes recent advances in the development of novel inhibitors targeting intracellular H2S biosynthesis in bacteria.