Citrate serves as a signal molecule to modulate carbon metabolism and iron homeostasis in Staphylococcus aureus.

Autor: Chen F; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.; College of Life Science, Northwest University, Xi'an, China.; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China., Zhao Q; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China., Yang Z; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China., Chen R; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China., Pan H; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China., Wang Y; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China., Liu H; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China., Cao Q; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China., Gan J; State Key Laboratory of Genetic Engineering, Shanghai Public Health Clinical Center, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China., Liu X; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; Department of Diving and Hyperbaric Medicine, Navy Medical Center, Naval Medical University, Shanghai, China., Zhang N; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China., Yang CG; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.; University of Chinese Academy of Sciences, Beijing, China., Liang H; College of Life Science, Northwest University, Xi'an, China.; School of Medicine, Southern University of Science and Technology, Shenzhen, China., Lan L; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.; College of Life Science, Northwest University, Xi'an, China.; Anhui Province Key Laboratory of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Jul 30; Vol. 20 (7), pp. e1012425. Date of Electronic Publication: 2024 Jul 30 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012425
Abstrakt: Pathogenic bacteria's metabolic adaptation for survival and proliferation within hosts is a crucial aspect of bacterial pathogenesis. Here, we demonstrate that citrate, the first intermediate of the tricarboxylic acid (TCA) cycle, plays a key role as a regulator of gene expression in Staphylococcus aureus. We show that citrate activates the transcriptional regulator CcpE and thus modulates the expression of numerous genes involved in key cellular pathways such as central carbon metabolism, iron uptake and the synthesis and export of virulence factors. Citrate can also suppress the transcriptional regulatory activity of ferric uptake regulator. Moreover, we determined that accumulated intracellular citrate, partly through the activation of CcpE, decreases the pathogenic potential of S. aureus in animal infection models. Therefore, citrate plays a pivotal role in coordinating carbon metabolism, iron homeostasis, and bacterial pathogenicity at the transcriptional level in S. aureus, going beyond its established role as a TCA cycle intermediate.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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