Hydrogen Sulfide Sensitizes Acinetobacter baumannii to Killing by Antibiotics

The production of endogenous hydrogen sulfide (H₂S) 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 H₂S. In this study, we established that the pathogenic bacteria Acinetobacter baumannii does not produce endogenous H₂S, giving us the opportunity to test the effect of exogenous H₂S on antibiotic tolerance in a bacterium that does not produce it. By using a H₂S-releasing compound to modulate the sulfide content in A. baumannii, we demonstrated that instead of conferring antibiotic tolerance, exogenous H₂S sensitized A. baumannii to multiple antibiotic classes, and was able to revert acquired resistance to gentamicin. Exogenous H₂S triggered a perturbation of redox and energy homeostasis that translated into hypersensitivity to antibiotic killing. We propose that H₂S could be used as an antibiotic-potentiator and resistance-reversion agent in bacteria that do not produce it.