Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Isovitexin Protects Mice from Methicillin-Resistant Staphylococcus aureus-Induced Pneumonia by Targeting Sortase A

  • Tian, Lili (Institute of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University) ;
  • Wu, Xinliang (Department of Pharmacy, Tianjin Baodi Hospital, Baodi Clinical College, Tianjin Medical University) ;
  • Yu, Hangqian (College of Animal Science, Jilin University) ;
  • Yang, Fengying (Institute of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University) ;
  • Sun, Jian (Department of Animal Husbandry and Veterinary Medicine, Beijing Vocational College Agriculture) ;
  • Zhou, Tiezhong (Institute of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University) ;
  • Jiang, Hong (Institute of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University)
  • Received : 2022.06.08
  • Accepted : 2022.09.30
  • Published : 2022.10.28
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Abstract

The rise of methicillin-resistant Staphylococcus aureus (MRSA) has resulted in significant morbidity and mortality, and clinical treatment of MRSA infections has become extremely difficult. Sortase A (SrtA), a virulence determinant that anchors numerous virulence-related proteins to the cell wall, is a prime druggable target against S. aureus infection due to its crucial role in the pathogenicity of S. aureus. Here, we demonstrate that isovitexin, an active ingredient derived from a variety of traditional Chinese medicines, can reversibly inhibit SrtA activity in vitrowith a low dose (IC50=24.72 ㎍/ml). Fluorescence quenching and molecular simulations proved the interaction between isovitexin and SrtA. Subsequent point mutation experiments further confirmed that the critical amino acid positions for SrtA binding to isovitexin were Ala-92, Ile-182, and Trp-197. In addition, isovitexin treatment dramatically reduced S. aureus invasion of A549 cells. This study shows that treatment with isovitexin could alleviate pathological injury and prolong the life span of mice in an S. aureus pneumonia model. According to our research, isovitexin represents a promising lead molecule for the creation of anti-S. aureus medicines or adjuncts.

Keywords

Acknowledgement

This work was supported by Science and technology project for people's livelihood of Liaoning province[grant numbers 2021JH2/10200009] the Natural Science Foundation of Liaoning province [grant numbers 20180550687, 2019-ZD-0614]

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