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

INTRODUCTION: Mycobacterium 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.

METHODS: In 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 DISCUSSION: The 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.