Covalent sortase A inhibitor, α, β-unsaturated aldehydes, prevents Staphylococcus aureus infection
文献类型：期刊论文
| 作者 | Wang, Jianchao2; He, Yuan2; Chu, Chenliang3; Wu, Ziqi2; Zhang, Ting2; Peng, Huayong2; Jin, Lu1 |
| 刊名 | MICROBIAL PATHOGENESIS
 |
| 出版日期 | 2025-07-01 |
| 卷号 | 204页码:12 |
| 关键词 | Sortase A Covalent inhibitor alpha beta-unsaturated aldehydes Anti-virulence therapy Staphylococcus aureus |
| ISSN号 | 0882-4010 |
| DOI | 10.1016/j.micpath.2025.107472 |
| 通讯作者 | Peng, Huayong(penghy29@163.com) ; Jin, Lu(jinlu0481@zidd.ac.cn) |
| 英文摘要 | Sortase A (SrtA) plays a crucial role in the attachment of virulence factors characterized by the LPXTG sequence to the peptidoglycans present on the cell wall surface, thereby rendering it a significant target for anti-virulence agents aimed at combating Staphylococcus aureus (S. aureus) infections. This study focuses on the compound 3, 3'(1,4-phenylene) diacrylaldehyde (DCA), selected as an anti-anchoring agent for covalent inhibitors. To elucidate the targets of DCA in inhibiting S. aureus and to investigate the molecular mechanism underlying the covalent inhibition of SrtA, proteomics and high-resolution mass spectrometry were employed. The findings indicate that compounds containing alpha, beta-unsaturated aldehydes can covalently modify the catalytic residue Cys184 of SrtA. This modification effectively inhibits the transpeptidation function of SrtA, which is responsible for cell wall anchoring, thereby obstructing the attachment of virulence factors such as IgG-SpA, FnbA, ClfA, Clfb, SdrC, Sas, and Can to the cell wall. As a result, this inhibition impedes immune evasion, biofilm formation, adhesion, and subsequent infection by S. aureus. Furthermore, it disrupts the NADH/NAD+ redox homeostasis and diminishes the virulence phenotype by interfering with the glycolytic pathway and the tricarboxylic acid (TCA) cycle of S. aureus. These findings confirm at the molecular level that compounds containing alpha, beta-unsaturated aldehydes possess the potential to serve as anti-virulence drugs that covalently inhibit SrtA. |
| WOS关键词 | NAD(+) |
| 资助项目 | National Natural Science Foundation of China Youth Program[82304804] ; Natural Science Foundation of Hunan Province[2024JJ7415] ; Excellent Youth Project of Education Department of Hunan Province[24B0501] |
| WOS研究方向 | Immunology ; Microbiology |
| 语种 | 英语 |
| WOS记录号 | WOS:001464469100001 |
| 出版者 | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317434]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Peng, Huayong; Jin, Lu |
| 作者单位 | 1.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Guangdong, Peoples R China 2.Jishou Univ, Sch Pharmaceut Sci, Key Lab Med Resources Chem & Pharmacol Wuling Moun, Jishou, Peoples R China 3.Zhaoqing Univ, Sch Food & Pharmaceut Engn, Zhaoqing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Jianchao,He, Yuan,Chu, Chenliang,et al. Covalent sortase A inhibitor, α, β-unsaturated aldehydes, prevents Staphylococcus aureus infection[J]. MICROBIAL PATHOGENESIS,2025,204:12. |
| APA | Wang, Jianchao.,He, Yuan.,Chu, Chenliang.,Wu, Ziqi.,Zhang, Ting.,...&Jin, Lu.(2025).Covalent sortase A inhibitor, α, β-unsaturated aldehydes, prevents Staphylococcus aureus infection.MICROBIAL PATHOGENESIS,204,12. |
| MLA | Wang, Jianchao,et al."Covalent sortase A inhibitor, α, β-unsaturated aldehydes, prevents Staphylococcus aureus infection".MICROBIAL PATHOGENESIS 204(2025):12. |
入库方式： OAI收割
来源：上海药物研究所
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