title: H2S: a universal defense against antibiotics in bacteria.
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.
authors.affiliation: Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Shatalin
authors.forename: Elena
authors.initials: E
authors.lastname: Shatalina
authors.forename: Alexander
authors.initials: A
authors.lastname: Mironov
authors.forename: Evgeny
authors.initials: E
authors.lastname: Nudler
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D001408:Bacillus anthracis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D024881:Drug Resistance, Bacterial; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013466:Sulfurtransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D009569:Nitric Oxide; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide