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Multi-omic analysis reveals lysine acylation and biofilm formation induced by central metabolites in methicillin-resistant Staphylococcus aureus

文献类型：期刊论文

作者Zhou, Changxia3,4; Chen, Mengying3,4; Wang, Rongzhen3; Liu, Xia3; Tian, Dabang3,4; Xiao, Mei3; Liu, Huiling3; Tian, Tian3; Sun, Yewen3; Tan, Minjia1,3,4
刊名MICROBIAL PATHOGENESIS
出版日期2026
卷号210页码:11
关键词Methicillin-resistant Staphylococcus aureus Central metabolism Biofilm formation Lysine acetylation Lysine succinylation Lysine lactylation Functional regulation
ISSN号0882-4010
DOI10.1016/j.micpath.2025.108198
英文摘要Methicillin-resistant Staphylococcus aureus (MRSA) is a major multidrug-resistant pathogen responsible for severe infections, such as pneumonia and bloodstream infections. These infections are often associated with high mortality rates and pose a significant burden on public health. Studies have shown that biofilm formation is a key factor contributing to its enhanced drug resistance. Recent evidence also implicates core metabolites in biofilm regulation. However, their specific regulatory mechanisms remain unclear. In this study, we initially assessed how key metabolites from glycolysis and the tricarboxylic acid (TCA) cycle influenced MRSA physiology. Notably, glucose markedly enhanced bacterial proliferation and stimulated biofilm development. To further explore the molecular basis of glucose-induced changes in MRSA, we subsequently applied a multidimensional omics approach, including proteomics, acetylomics, succinylomics, and lactylomics. A total of 1666 proteins, 3761 lysine acetylated sites, 1809 succinylated sites, and 128 lactylated sites were identified by high-resolution mass spectrometry. Subsequent bioinformatic analysis revealed that these modifications were significantly enriched in ribosome-associated functions and metabolic pathways. To further explore their functional relevance, in vitro enzyme assays demonstrated that glucose-induced lysine succinylation modulates the activity of arsenate reductase. Building upon this, functional validation at both the bacterial and host cell levels confirmed the physiological significance of glucose-induced lysine acylation. In conclusion, these findings reveal that the core metabolite glucose promotes MRSA biofilm formation and induces extensive lysine acylation, which in turn regulates metabolic functions and virulence. Therefore, this study provides new insights into MRSA pathogenesis and suggests potential targets for anti-infective therapy.
WOS关键词ACETYLATION
资助项目National Natural Science Foundation of China[32322048] ; National Natural Science Foundation of China[32471497] ; National Natural Science Foundation of China[22225702] ; National Natural Science Foundation of China[T2488301] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB1360000] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB0830000] ; Program of Shanghai Academic Research Leader[22XD1420900] ; Zhongshan Science and Technology Bureau[CXTD2024006] ; National Key Research and Development Program of China[2021YFA0804701] ; National Key Research and Development Program of China[2023YFA1800400] ; National Key Research and Development Program of China[2023YFA1800403] ; Innovative Research Team of High-Level Local Universities in Shanghai, Young Elite Scientists Sponsorship Program by CAST[2022QNRC001] ; Shanghai Rising-Star Program[22QA1411100] ; Youth Innovation Promotion Association[CAS2021276] ; Sanofi scholarship program ; Guangdong High-level New R&D Institute, China[:2019B090904008] ; Guangdong High-level Innovative Research Institute, China[:2021B0909050003]
WOS研究方向Immunology ; Microbiology
语种英语
WOS记录号WOS:001629559300001
出版者ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/322163]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Sun, Yewen; Tan, Minjia; Xu, Jun-Yu
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Key Lab Gene Editing & Cell Based Immunot, Sch Med, Shanghai 200025, Peoples R China
3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Jiangsu, Peoples R China
推荐引用方式
GB/T 7714		 Zhou, Changxia,Chen, Mengying,Wang, Rongzhen,et al. Multi-omic analysis reveals lysine acylation and biofilm formation induced by central metabolites in methicillin-resistant Staphylococcus aureus[J]. MICROBIAL PATHOGENESIS,2026,210:11.
APA Zhou, Changxia.,Chen, Mengying.,Wang, Rongzhen.,Liu, Xia.,Tian, Dabang.,...&Xu, Jun-Yu.(2026).Multi-omic analysis reveals lysine acylation and biofilm formation induced by central metabolites in methicillin-resistant Staphylococcus aureus.MICROBIAL PATHOGENESIS,210,11.
MLA Zhou, Changxia,et al."Multi-omic analysis reveals lysine acylation and biofilm formation induced by central metabolites in methicillin-resistant Staphylococcus aureus".MICROBIAL PATHOGENESIS 210(2026):11.

入库方式： OAI收割

来源：上海药物研究所

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