Modulation of MRSA virulence gene expression by the wall teichoic acid enzyme TarO
文献类型：期刊论文
| 作者 | Lu, Yunfu5,6,7; Chen, Feifei4,6,7; Zhao, Qingmin5,6,7; Cao, Qiao4,6,7; Chen, Rongrong5,6,7; Pan, Huiwen5,6,7; Wang, Yanhui5,6,7; Huang, Haixin6; Huang, Ruimin5,6 ; Liu, Qian3
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| 刊名 | NATURE COMMUNICATIONS
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| 出版日期 | 2023-03-22 |
| 卷号 | 14期号:1页码:19 |
| DOI | 10.1038/s41467-023-37310-5 |
| 通讯作者 | Liang, Haihua(lianghh@sustech.edu.cn) ; Lan, Lefu(llan@ucas.ac.cn) |
| 英文摘要 | Phenol-soluble modulins (PSMs) and Staphylococcal protein A (SpA) are key virulence determinants for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), an important human pathogen that causes a wide range of diseases. Here, using chemical and genetic approaches, we show that inhibition of TarO, the first enzyme in the wall teichoic acid (WTA) biosynthetic pathway, decreases the expression of genes encoding PSMs and SpA in the prototypical CA-MRSA strain USA300 LAC. Mechanistically, these effects are linked to the activation of VraRS two-component system that directly represses the expression of accessory gene regulator (agr) locus and spa. The activation of VraRS was due in part to the loss of the functional integrity of penicillin-binding protein 2 (PBP2) in a PBP2a-dependent manner. TarO inhibition can also activate VraRS in a manner independent of PBP2a. We provide multiple lines of evidence that accumulation of lipid-linked peptidoglycan precursors is a trigger for the activation of VraRS. In sum, our results reveal that WTA biosynthesis plays an important role in the regulation of virulence gene expression in CA-MRSA, underlining TarO as an attractive target for anti-virulence therapy. Our data also suggest that acquisition of PBP2a-encoding mecA gene can impart an additional regulatory layer for the modulation of key signaling pathways in S. aureus. |
| WOS关键词 | BETA-LACTAM RESISTANCE ; STAPHYLOCOCCUS-AUREUS ; CELL-WALL ; LIPID-II ; METHICILLIN RESISTANCE ; CROSS-LINKING ; BINDING ; BIOSYNTHESIS ; PATHWAY ; SIGNAL |
| 资助项目 | National Natural Science Foundation (NSFC)[32270184] ; National Natural Science Foundation (NSFC)[31870127] ; Science and Technology Commission of Shanghai Municipality[19JC1416400] ; State Key Laboratory of Drug Research[SIMM2003ZZ-03] ; State Key Laboratory of Drug Research[SIMM2205KF-07] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PORTFOLIO |
| WOS记录号 | WOS:001063479500020 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/307161]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liang, Haihua; Lan, Lefu |
| 作者单位 | 1.Southern Univ Sci & Technol, Sch Med, Shenzhen 518055, Peoples R China 2.Indiana Univ Sch Med Northwest, Dept Microbiol & Immunol, Gary, IN 46408 USA 3.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Lab Med, Shanghai 200127, Peoples R China 4.Northwest Univ, Coll Life Sci, Xian 710127, Peoples R China 5.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 7.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lu, Yunfu,Chen, Feifei,Zhao, Qingmin,et al. Modulation of MRSA virulence gene expression by the wall teichoic acid enzyme TarO[J]. NATURE COMMUNICATIONS,2023,14(1):19. |
| APA | Lu, Yunfu.,Chen, Feifei.,Zhao, Qingmin.,Cao, Qiao.,Chen, Rongrong.,...&Lan, Lefu.(2023).Modulation of MRSA virulence gene expression by the wall teichoic acid enzyme TarO.NATURE COMMUNICATIONS,14(1),19. |
| MLA | Lu, Yunfu,et al."Modulation of MRSA virulence gene expression by the wall teichoic acid enzyme TarO".NATURE COMMUNICATIONS 14.1(2023):19. |
入库方式： OAI收割
来源：上海药物研究所
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