H2S: A Universal Defense Against Antibiotics in Bacteria

Many prokaryotic species generate hydrogen sulfide (H2S) in their natural environments. However, the biochemistry and physiological role of this gas in nonsulfur bacteria remain largely unknown. Here we demonstrate that inactivation of putative cystathionine beta-synthase, cystathionine gamma-lyase, or 3-mercaptopyruvate sulfurtransferase in Bacillus anthracis, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli suppresses H2S production, rendering these pathogens highly sensitive to a multitude of antibiotics. Exogenous H2S suppresses this effect. Moreover, in bacteria that normally produce H2S and nitric oxide, these two gases act synergistically to sustain growth. The mechanism of gas-mediated antibiotic resistance relies on mitigation of oxidative stress imposed by antibiotics.