Hydrogen Sulfide Sensitizes to Killing by Antibiotics.

The production of endogenous hydrogen sulfide (HS) has been shown to confer antibiotic tolerance in all bacteria studied to date. Therefore, this mediator has been speculated to be a universal defense mechanism against antibiotics in bacteria. This is assuming that all bacteria produce endogenous HS. In this study, we established that the pathogenic bacteria does not produce endogenous HS, giving us the opportunity to test the effect of exogenous HS on antibiotic tolerance in a bacterium that does not produce it. By using a HS-releasing compound to modulate the sulfide content in , we demonstrated that instead of conferring antibiotic tolerance, exogenous HS sensitized to multiple antibiotic classes, and was able to revert acquired resistance to gentamicin. Exogenous HS triggered a perturbation of redox and energy homeostasis that translated into hypersensitivity to antibiotic killing. We propose that HS could be used as an antibiotic-potentiator and resistance-reversion agent in bacteria that do not produce it.