Frontiers in Pharmacology (Dec 2022)
The synergistic activity of SBC3 in combination with Ebselen against Escherichia coli infection
- Hao Chen,
- Hao Chen,
- Qianqian Lu,
- Qianqian Lu,
- Haoyue An,
- Haoyue An,
- Juntong Li,
- Juntong Li,
- Shuchu Shen,
- Shuchu Shen,
- Xi Zheng,
- Xi Zheng,
- Wei Chen,
- Wei Chen,
- Lu Wang,
- Lu Wang,
- Jihong Li,
- Jihong Li,
- Youqin Du,
- Youqin Du,
- Yueqing Wang,
- Yueqing Wang,
- Xiaowen Liu,
- Xiaowen Liu,
- Marcus Baumann,
- Matthias Tacke,
- Lili Zou,
- Lili Zou,
- Lili Zou,
- Lili Zou,
- Jun Wang
Affiliations
- Hao Chen
- The Second People’s Hospital of China Three Gorges University, Yichang, Hubei, China
- Hao Chen
- The Second People’s Hospital of Yichang, Yichang, Hubei, China
- Qianqian Lu
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Qianqian Lu
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Haoyue An
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Haoyue An
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Juntong Li
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Juntong Li
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Shuchu Shen
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Shuchu Shen
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Xi Zheng
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Xi Zheng
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Wei Chen
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Wei Chen
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Lu Wang
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Lu Wang
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Jihong Li
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Jihong Li
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Youqin Du
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Youqin Du
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Yueqing Wang
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Yueqing Wang
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Xiaowen Liu
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Xiaowen Liu
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Marcus Baumann
- The School of Chemistry, University College Dublin, Belfield, Dublin, Ireland
- Matthias Tacke
- The School of Chemistry, University College Dublin, Belfield, Dublin, Ireland
- Lili Zou
- The Second People’s Hospital of China Three Gorges University, Yichang, Hubei, China
- Lili Zou
- The Second People’s Hospital of Yichang, Yichang, Hubei, China
- Lili Zou
- Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Lili Zou
- The Institute of Infection and Inflammation, College of Basic Medical Sciences, China Three Gorges University, Yichang, Hubei, China
- Jun Wang
- The People’s Hospital of China Three Gorges University, Yichang, Hubei, China
- DOI
- https://doi.org/10.3389/fphar.2022.1080281
- Journal volume & issue
-
Vol. 13
Abstract
Escherichia coli ranks as the number one clinical isolate in the past years in China according to The China Antimicrobial Surveillance Network (CHINET), and its multidrug-resistant (MDR) pathogenic strains account for over 160 million cases of dysentery and one million deaths per year. Here, our work demonstrates that E. coli is highly sensitive to the synergistic combination of SBC3 [1,3-Dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver (I) acetate] and Ebselen, which shows no synergistic toxicity on mammalian cells. The proposed mechanism for the synergistic antibacterial effect of SBC3 in combination with Ebselen is based on directly inhibiting E. coli thioredoxin reductase and rapidly depleting glutathione, resulting in the increase of reactive oxygen species that cause bacterial cell death. Furthermore, the bactericidal efficacy of SBC3 in combination with Ebselen has been confirmed in mild and acute peritonitis mice. In addition, the five most difficult to treat Gram-negative bacteria (including E. coli, Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa) are also highly sensitive to a synergistic combination of SBC3 and Ebselen. Thus, SBC3 in combination with Ebselen has potential as a treatment for clinically important Gram-negative bacterial infections.
Keywords
- SBC3
- ebselen (PubChem CID: 3194)
- Escherichia coli
- thiol-dependent redox system
- peritonitis
- redox homeostasis
