期刊
CELL CHEMICAL BIOLOGY
卷 27, 期 12, 页码 1483-+出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2020.10.012
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资金
- National Natural Science Foundation of China [31870763, 21834005]
- Natural Science Foundation of Shanghai [18ZR1419500]
- Shanghai Foundation for the Development of Science and Technology [19JC1413000]
- Research Fund of Medicine and Engineering of Shanghai Jiao Tong University [YG2017MS51 YG2019QNB27]
H2S-producing enzymes in bacteria have been shown to be closely engaged in the process of microbial survival and antibiotic resistance. However, no inhibitors have been discovered for these enzymes, e.g., 3-mercaptopyruvate sulfurtransferase (MST). In the present study, we identified several classes of inhibitors for Escherichia coli MST (eMST) through high-throughput screening of similar to 26,000 compounds. The thiazolidinedione-type inhibitors were found to selectively bind to Arg178 and Ser239 residues of eMST but hardly affected human MST. Moreover, the pioglitazone of this class concentration dependently accumulates the 3-mercaptopyruvate substrate and suppresses the H2S and reactive sulfane sulfur products in bacteria. Importantly, pioglitazone could potentiate the level of reactive oxygen species in cellulo and consequently enhance the antimicrobial effects of gentamicin and macrophages in culture. This study has identified the bioactive inhibitor of eMST, paving the way for the pharmacological targeting of eMST to synergistically control the survival of E. coli.
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