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. 2020 Dec;114(6):1038-1048.
doi: 10.1111/mmi.14593. Epub 2020 Sep 20.

Sulfane Sulfur is an intrinsic signal activating MexR-regulated antibiotic resistance in Pseudomonas aeruginosa

Guanhua Xuan  1 , Chuanjuan Lü  1 , Huangwei Xu  1 , Zhigang Chen  1 , Kai Li  1 , Honglei Liu  1 , Huaiwei Liu  1 , Yongzhen Xia  1 , Luying Xun  1   2
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Sulfane Sulfur is an intrinsic signal activating MexR-regulated antibiotic resistance in Pseudomonas aeruginosa

Guanhua Xuan et al. Mol Microbiol. 2020 Dec.
Free article

Abstract

Pseudomonas aeruginosa PAO1, an opportunistic human pathogen, deploys several strategies to resist antibiotics. It uses multidrug efflux pumps, including the MexAB-OprM pump, for antibiotic resistance, and it also produces hydrogen sulfide (H2 S) that provides some defense against antibiotics. MexR functions as a transcriptional repressor of the mexAB-oprM operon. MexR responds to oxidative stresses caused by antibiotic exposure, and it also displays a growth phase-dependent derepression of the mexAB-oprM operon. However, the intrinsic inducer has not been identified. Here, we report that P. aeruginosa PAO1 produced sulfane sulfur, including glutathione persulfide and inorganic polysulfide, produced from either H2 S oxidation or from L-cysteine metabolism. Sulfane sulfur directly reacted with MexR, forming di- and trisulfide cross-links between two Cys residues, to derepress the mexAB-oprM operon. Levels of cellular sulfane sulfur and mexAB-oprM expression varied during growth, and both reached the maximum during the stationary phase of growth. Thus, self-produced H2 S and sulfane sulfur may facilitate antibiotic resistance via inducing the expression of antibiotic resistance genes.

Keywords: Pseudomonas aeruginosa; H2S; MexR; antibiotic resistance; sulfane sulfur.

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References

REFERENCES

    1. Akaike, T., Ida, T., Wei, F.Y., Nishida, M., Kumagai, Y., Alam, M.M., et al. (2017) Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. Nature Communications, 8, 1177.
    1. Belenky, P., Ye, J.D., Porter, C.B.M., Cohen, N.R., Lobritz, M.A., Ferrante, T., et al. (2015) Bactericidal antibiotics induce toxic metabolic perturbations that lead to cellular damage. Cell Reports, 13, 968-980.
    1. Bibli, S.I., Luck, B., Zukunft, S., Wittig, J., Chen, W., Xian, M., et al. (2018) A selective and sensitive method for quantification of endogenous polysulfide production in biological samples. Redox Biology, 18, 295-304.
    1. Breidenstein, E.B., de la Fuente-Nunez, C. and Hancock, R.E. (2011) Pseudomonas aeruginosa: all roads lead to resistance. Trends in Microbiology, 19, 419-426.
    1. Chen, H., Hu, J., Chen, P.R., Lan, L.F., Li, Z.L., Hicks, L.M., et al. (2008) The Pseudomonas aeruginosa multidrug efflux regulator MexR uses an oxidation-sensing mechanism. Proceedings of the National Academy of Sciences of the United States of America, 105, 13586-13591.

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