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XthA phospholipase contributes the cell-wall functionality of pathogenic mycobacteria by increasing the synthesis of mycolic acid

文献类型： 外文期刊

作者： Jiang, Yanyan 1 ; Zang, Xinxin 1 ; Feng, Tingting 1 ; Wang, Hui 1 ; Cui, Ning 1 ; Duan, Yifan 1 ; Chen, Chunwen 1 ; Zhang, Zhenjun 1 ; Guo, Ruonan 1 ; Gao, Yunjie 1 ; Cui, Yingying 1 ; Dang, Guanghui 1 ; Liu, Siguo 1 ;

作者机构： 1.Chinese Acad Agr Sci, Harbin Vet Res Inst, Div Bacterial Dis, State Key Lab Anim Dis Control & Prevent, 678 Haping St, Harbin 150069, Heilongjiang, Peoples R China

2.Zhejiang A&F Univ, Key Lab Appl Technol Green Ecohlth Anim Husb Zheji, Zhejiang Prov Engn Lab Anim Hlth Inspect & Interne, China Australia Joint Lab Anim Hlth Big Data Analy, Hangzhou 311300, Zhejiang, Peoples R China

3.Zhejiang A&F Univ, Coll Vet Med, Hangzhou 311300, Zhejiang, Peoples R China

4.Shanghai Key Lab Vet Biotechnol, Shanghai 200240, Peoples R China

关键词： Mycobacterial phospholipase; Cell wall; Mycolic acid

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.5； 五年影响因子：8.7 ）

ISSN： 0141-8130

年卷期： 2025 年 319 卷

页码：

收录情况： SCI

摘要： The mycobacterial cell wall is a complex structure that plays a critical role in resisting external environmental stress and contributing to pathogenesis, with mycolic acid being a key component in maintaining cell wall integrity. Moreover, the enzymes involved in cell wall synthesis are frequently targeted in antimycobacterial drug research. In this study, we demonstrate that the conserved extracellular DNase XthA from mycobacteria exhibits phospholipase A1 (PLA1) activity, whereas this activity is absent in non-pathogenic mycobacteria. Moreover, XthA PLA1 activity facilitates the formation of cord-like structures, promotes the proliferation of mycobacteria, and enhances their resistance to environmental stressors. Results from ethidium bromide and minimum inhibitory concentration assays suggest that XthA PLA1 activity reduces the permeability of the mycobacterial cell wall. Furthermore, analyses using scanning electron microscopy and mass spectrometry demonstrated that PLA1 activity contributes to cell wall integrity and enhances the synthesis of mycolic acids. Additionally, qPCR analysis indicated that XthA PLA1 activity upregulates the transcript of key genes involved in the MAs synthesis pathway. Collectively, these findings suggest that pathogenic mycobacteria utilize XthA PLA1 to facilitate cell wall functionality by regulating mycolic acid synthesis, thereby underscoring its potential as a drug target for disrupting the cell wall of pathogenic mycobacteria.

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