Post-translational toxin modification by lactate controls Staphylococcus aureus virulence

Yanan Wang, Yanfeng Liu, Guoxiu Xiang, Ying Jian, Ziyu Yang, Tianchi Chen, Xiaowei Ma, Na Zhao, Yingxin Dai, Yan Lv, Hua Wang, Lei He, Bisheng Shi, Qian Liu, Yao Liu, Michael Otto () and Min Li ()
Additional contact information
Yanan Wang: Shanghai Jiao Tong University
Yanfeng Liu: Shanghai Jiao Tong University
Guoxiu Xiang: Shanghai Jiao Tong University
Ying Jian: Shanghai Jiao Tong University
Ziyu Yang: Shanghai Jiao Tong University
Tianchi Chen: Shanghai Jiao Tong University
Xiaowei Ma: Shanghai Jiao Tong University
Na Zhao: Shanghai Jiao Tong University
Yingxin Dai: Shanghai Jiao Tong University
Yan Lv: Shanghai Jiao Tong University
Hua Wang: Shanghai Jiao Tong University
Lei He: Shanghai Jiao Tong University
Bisheng Shi: Shanghai Jiao Tong University
Qian Liu: Shanghai Jiao Tong University
Yao Liu: Shanghai Jiao Tong University
Michael Otto: National Institutes of Health
Min Li: Shanghai Jiao Tong University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Diverse post-translational modifications have been shown to play important roles in regulating protein function in eukaryotes. By contrast, the roles of post-translational modifications in bacteria are not so well understood, particularly as they relate to pathogenesis. Here, we demonstrate post-translational protein modification by covalent addition of lactate to lysine residues (lactylation) in the human pathogen Staphylococcus aureus. Lactylation is dependent on lactate concentration and specifically affects alpha-toxin, in which a single lactylated lysine is required for full activity and virulence in infection models. Given that lactate levels typically increase during infection, our results suggest that the pathogen can use protein lactylation as a mechanism to increase toxin-mediated virulence during infection.

Date: 2024
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DOI: 10.1038/s41467-024-53979-8

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