H ₂ S: A Universal Defense Against Antibiotics in Bacteria

TLDR

Many prokaryotic species produce hydrogen sulfide (H₂S), yet its biochemical and physiological roles in nonsulfur bacteria remain largely unknown. H₂S confers antibiotic resistance by mitigating the oxidative stress imposed by antibiotics. Loss of H₂S production by disrupting key sulfurtransferases in *B.

Abstract

Many prokaryotic species generate hydrogen sulfide (H(2)S) 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 β-synthase, cystathionine γ-lyase, or 3-mercaptopyruvate sulfurtransferase in Bacillus anthracis, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli suppresses H(2)S production, rendering these pathogens highly sensitive to a multitude of antibiotics. Exogenous H(2)S suppresses this effect. Moreover, in bacteria that normally produce H(2)S 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.