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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Anti-Bacterial Agents / pharmacology*
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Antioxidants / metabolism
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Bacillus anthracis / drug effects
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Bacillus anthracis / growth & development
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Bacillus anthracis / metabolism
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Bacteria / drug effects*
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Bacteria / growth & development
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Bacteria / metabolism*
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Cystathionine beta-Synthase / antagonists & inhibitors
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Cystathionine beta-Synthase / genetics
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Cystathionine beta-Synthase / metabolism
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Cystathionine gamma-Lyase / antagonists & inhibitors
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Cystathionine gamma-Lyase / genetics
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Cystathionine gamma-Lyase / metabolism
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DNA Breaks, Double-Stranded
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Drug Resistance, Bacterial
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Drug Resistance, Multiple, Bacterial*
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Escherichia coli / drug effects
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Escherichia coli / growth & development
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Escherichia coli / metabolism
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Hydrogen Sulfide / metabolism*
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Hydrogen Sulfide / pharmacology
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Molecular Sequence Data
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Nitric Oxide / metabolism
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Oxidative Stress
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Pseudomonas aeruginosa / drug effects
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Pseudomonas aeruginosa / growth & development
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Pseudomonas aeruginosa / metabolism
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Staphylococcus aureus / drug effects
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Staphylococcus aureus / growth & development
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Staphylococcus aureus / metabolism
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Sulfurtransferases / antagonists & inhibitors
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Sulfurtransferases / genetics
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Sulfurtransferases / metabolism
Substances
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Anti-Bacterial Agents
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Antioxidants
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Nitric Oxide
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Sulfurtransferases
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3-mercaptopyruvate sulphurtransferase
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Cystathionine beta-Synthase
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Cystathionine gamma-Lyase
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Hydrogen Sulfide