H ₂ S: 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.

Key bioactive reaction products of the NO/H 2 S interaction are S/N-hybrid species, polysulfides, and nitroxyl

“…In any case, our findings open the door to a new field of research with SSNO − , HS n − , and SULFI/NO taking center stage as biologically important mediators of both the NO and H 2 S transduction pathways. Although the cardiovascular system has been the target of our current efforts, this chemical interaction is likely to be relevant to cell/organelle signaling in many other systems, including neuronal and immune cells, plants, and prokaryotes as exemplified by the recent work on antibiotic resistance by bacterial NO/H 2 S production (17). Beyond its likely significance for biology and redox signaling, our results may also be of significance for environmental chemistry pertinent to marine and atmospheric processes.…”

“…The recent surge of interest in this chemistry in the biological community (13)(14)(15) was triggered by a growing appreciation that NO and sulfide exert similar and often interdependent biological actions within the cardiovascular system and elsewhere (NO/H 2 S "cross-talk") (16,17), resulting in mutual attenuation or potentiation of their responses. This crosstalk is possibly mediated by chemical interactions (18)(19)(20), but much of the older chemical work seems to have been forgotten.…”

Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals

“…Tolerance to antibiotics may therefore depend on the ability of the cell to defend itself against ROS, as suggested by several recent studies (28)(29)(30). For example, the coordinated stringent response to nutrient limitation in P. aeruginosa and E. coli was shown to increase antioxidant enzyme expression and decrease production of prooxidant molecules, resulting in antibiotic tolerance (28).…”

“…For example, the coordinated stringent response to nutrient limitation in P. aeruginosa and E. coli was shown to increase antioxidant enzyme expression and decrease production of prooxidant molecules, resulting in antibiotic tolerance (28). Bacteria also produce nitric oxide (NO) as well as hydrogen sulfide (H 2 S), both of which result in antibiotic tolerance via suppression of the Fenton reaction as well as increased antioxidant enzyme expression in both Gram-positive and Gramnegative bacteria (29,30).…”

Volatile affairs in microbial interactions

“…However, this phenomenon appeared to result from pH increase in the media caused by bacterial volatiles rather than by alteration of specific traits in the target bacterium. Another inorganic volatile compound, hydrogen sulphide, was suggested as a universal defence against antibiotics in bacteria as it seemed to trigger broad-spectrum antibiotic resistance, most probably due to alleviation of oxidative stress (Shatalin et al, 2011).…”