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Sulfane Sulfur is an intrinsic signal activating MexR-regulated antibiotic resistance in Pseudomonas aeruginosa.
Molecular Microbiology ( IF 3.6 ) Pub Date : 2020-09-01 , DOI: 10.1111/mmi.14593
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
Affiliation  

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 (H2S) 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 H2S 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 H2S and sulfane sulfur may facilitate antibiotic resistance via inducing the expression of antibiotic resistance genes.

中文翻译:

Sulfane Sulfur 是激活铜绿假单胞菌中 MexR 调节的抗生素耐药性的内在信号。

铜绿假单胞菌PAO1 是一种机会性人类病原体,它采用多种策略来抵抗抗生素。它使用多药外排泵(包括 MexAB-OprM 泵)来提高抗生素抗性,并且还产生硫化氢 (H 2 S),从而提供一些针对抗生素的防御。MexR 作为mexAB-oprM操纵子的转录抑制因子起作用。MexR 对由抗生素暴露引起的氧化应激作出反应,并且它还显示出mexAB-oprM操纵子的生长阶段依赖性去抑制。然而,内在诱导剂尚未确定。在这里,我们报告铜绿假单胞菌PAO1 产生硫烷硫,包括谷胱甘肽过硫化物和无机多硫化物,由 H2 S 氧化或来自 L-半胱氨酸代谢。硫烷硫直接与 MexR 反应,在两个 Cys 残基之间形成二硫化物和三硫化物交联,以解除mexAB-oprM操纵子的抑制。细胞中硫烷硫和mexAB-oprM 的表达水平在生长过程中发生变化,并且在生长的稳定期达到最大值。因此,自产H 2 S和硫烷硫可以通过诱导抗生素抗性基因的表达来促进抗生素抗性。
更新日期:2020-09-01
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