Deletion of the Mycobacterium tuberculosis cyp138 gene leads to changes in membrane-related lipid composition and antibiotic susceptibility

Yun Lu; Yun Lu; Hongtong Chen; Hongtong Chen; Hongtong Chen; Zhiyuan Shao; Zhiyuan Shao; Zhiyuan Shao; Lang Sun; Lang Sun; Lang Sun; Congran Li; Congran Li; Yu Lu; Xuefu You; Xuefu You; Xuefu You; Xinyi Yang; Xinyi Yang

doi:10.3389/fmicb.2024.1301204

Frontiers in Microbiology (Mar 2024)

Deletion of the Mycobacterium tuberculosis cyp138 gene leads to changes in membrane-related lipid composition and antibiotic susceptibility

Yun Lu,
Yun Lu,
Hongtong Chen,
Hongtong Chen,
Hongtong Chen,
Zhiyuan Shao,
Zhiyuan Shao,
Zhiyuan Shao,
Lang Sun,
Lang Sun,
Lang Sun,
Congran Li,
Congran Li,
Yu Lu,
Xuefu You,
Xuefu You,
Xuefu You,
Xinyi Yang,
Xinyi Yang

Affiliations

Yun Lu: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Yun Lu: Division for Medicinal Microorganisms-related Strains, CAMS Collection Center of Pathogenic Microorganisms, Beijing, China
Hongtong Chen: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Hongtong Chen: Division for Medicinal Microorganisms-related Strains, CAMS Collection Center of Pathogenic Microorganisms, Beijing, China
Hongtong Chen: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Zhiyuan Shao: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Zhiyuan Shao: Division for Medicinal Microorganisms-related Strains, CAMS Collection Center of Pathogenic Microorganisms, Beijing, China
Zhiyuan Shao: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Lang Sun: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Lang Sun: Division for Medicinal Microorganisms-related Strains, CAMS Collection Center of Pathogenic Microorganisms, Beijing, China
Lang Sun: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Congran Li: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Congran Li: Division for Medicinal Microorganisms-related Strains, CAMS Collection Center of Pathogenic Microorganisms, Beijing, China
Yu Lu: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, and Beijing Chest Hospital, Capital Medical University, Beijing, China
Xuefu You: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Xuefu You: Division for Medicinal Microorganisms-related Strains, CAMS Collection Center of Pathogenic Microorganisms, Beijing, China
Xuefu You: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Xinyi Yang: Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Xinyi Yang: Division for Medicinal Microorganisms-related Strains, CAMS Collection Center of Pathogenic Microorganisms, Beijing, China

DOI: https://doi.org/10.3389/fmicb.2024.1301204
Journal volume & issue: Vol. 15

Abstract

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IntroductionMycobacterium tuberculosis (Mtb), the main cause of tuberculosis (TB), has brought a great burden to the world's public health. With the widespread use of Mtb drug-resistant strains, the pressure on anti-TB treatment is increasing. Anti-TB drugs with novel structures and targets are urgently needed. Previous studies have revealed a series of CYPs with important roles in the survival and metabolism of Mtb. However, there is little research on the structure and function of CYP138.MethodsIn our study, to discover the function and targetability of CYP138, a cyp138-knockout strain was built, and the function of CYP138 was speculated by the comparison between cyp138-knockout and wild-type strains through growth curves, growth status under different carbon sources, infection curves, SEM, MIC tests, quantitative proteomics, and lipidomics.Results and discussionThe knockout of cyp138 was proven to affect the Mtb's macrophage infection, antibiotics susceptibility, and the levels of fatty acid metabolism, membrane-related proteins, and lipids such as triacylglycerol. We proposed that CYP138 plays an important role in the synthesis and decomposition of lipids related to the cell membrane structure as a new potential anti-tuberculosis drug target.

Published in Frontiers in Microbiology

ISSN: 1664-302X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.frontiersin.org/journals/microbiology

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