Post-translational toxin modification by lactate controls Staphylococcus aureus virulence
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.
Authors
- Yingxin Dai (ORCID: https://orcid.org/0009-0009-6827-9312)
- Yanan Wang (ORCID: https://orcid.org/0000-0002-8864-5609)
- Guoxiu Xiang
- Bisheng Shi
- Michaël Otto (ORCID: https://orcid.org/0000-0002-2222-4115)
- Wenlong Yang (ORCID: https://orcid.org/0000-0003-3139-2767)
- Yan Lv (ORCID: https://orcid.org/0000-0001-7387-7477)
- Qian Liu (ORCID: https://orcid.org/0000-0001-8897-5117)
- Hua Wang (ORCID: https://orcid.org/0000-0003-2633-3420)
- Yao Liu (ORCID: https://orcid.org/0000-0002-7151-870X)
- Yanfeng Liu (ORCID: https://orcid.org/0000-0003-2633-4765)
- Ying Jian (ORCID: https://orcid.org/0000-0001-5185-2455)
- Na Zhao (ORCID: https://orcid.org/0000-0002-8417-7895)
- Xiaowei Ma (ORCID: https://orcid.org/0000-0003-3245-0930)
- Min Li (ORCID: https://orcid.org/0000-0002-8571-2909)
- Tianchi Chen
- Lei He (ORCID: https://orcid.org/0000-0003-4679-5462)
Institutions
- National Institutes of Health (US)
- Shanghai Jiao Tong University (CN)
- Renji Hospital (CN)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-13
- DOI
- https://doi.org/10.1038/s41467-024-53979-8
- Citations
- 18
- Primary Topic
- Antimicrobial Resistance in Staphylococcus
- Type
- article
- Field-Weighted Citation Impact
- 7.00
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- National Institute of Allergy and Infectious Diseases