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

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

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1301204

DOI=10.3389/fmicb.2024.1301204

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p><italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>), the main cause of tuberculosis (TB), has brought a great burden to the world's public health. With the widespread use of <italic>Mtb</italic> 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 <italic>Mtb</italic>. However, there is little research on the structure and function of CYP138.</p></sec><sec><title>Methods</title><p>In our study, to discover the function and targetability of CYP138, a <italic>cyp138</italic>-knockout strain was built, and the function of CYP138 was speculated by the comparison between <italic>cyp138</italic>-knockout and wild-type strains through growth curves, growth status under different carbon sources, infection curves, SEM, MIC tests, quantitative proteomics, and lipidomics.</p></sec><sec><title>Results and discussion</title><p>The knockout of <italic>cyp138</italic> was proven to affect the <italic>Mtb</italic>'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.</p></sec>