Dataset Information

PatA mediates biofilm formation and drugs resistance through regulating the synthesis of glycolipids and lipids in mycobacterium PatA mediates a novel mycolic acid synthesis pathway and regulates biofilm formation in mycobacterium

ABSTRACT: Glycolipids and lipids are prominent components of bacterial cell wall that play critical roles not only in maintaining the biofilm formation but also in resistance to environmental stress. PatA is an essential membrane associated acyltransferase involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIMs), which are the key glycolipid components in the cell wall of Mycobacterium tuberculosis. However, whether or not PatA regulates the lipids synthesis and affects drugs resistance and biofilm formation in mycobacterium is unclear, and the mechanisms involved remain to be explored. Here we show that PatA can directly regulate the synthesis of glycolipids and lipids to maintain the drugs resistance and biofilm formation in Mycobacterium smegmatis. Interestingly, the INH resistance of patA-deleted mutant is significantly enhanced although its biofilm formation is reduced. This is due to PatA negative regulation the synthesis of mycolic acids through a novel mycolic acid synthesis pathway other than the FAS pathway, which could efficiently counteract the inhibition of isoniazid on mycolic acids synthesis in mycobacterium. Furthermore, PatA is highly conserved including amino acid sequences and physiological functions in mycobacterium. Therefore, PatA regulates the synthesis of glycolipids and lipids to affect drugs resistance and biofilm formation in mycobacterium. Our findings provide a novel mycolic acids synthetic pathway and novel insights into the molecular mechanism of glycolipids and lipids metabolism regulation and their correlation with bacterial physiological phenotypes.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS6758 | MetaboLights | 2023-05-22

REPOSITORIES: MetaboLights

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Source:

			Action	DRS
	HFX3_497960_CN_QC_ddMS2-114-610.mzML	Mzml
	HFX3_497960_CN_QC_ddMS2-600-810.mzML	Mzml
	HFX3_497960_CN_QC_ddMS2-800-1710.mzML	Mzml
	HFX5_497960_CN_QC1.mzML	Mzml
	HFX5_497960_CN_QC2.mzML	Mzml

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Publications

PatA Regulates Isoniazid Resistance by Mediating Mycolic Acid Synthesis and Controls Biofilm Formation by Affecting Lipid Synthesis in Mycobacteria.

Wang Kun K Deng Yimin Y Cui Xujie X Chen Mengli M Ou Yanzhe Y Li Danting D Guo Minhao M Li Weihui W

Microbiology spectrum 20230522 3

Lipids are prominent components of the mycobacterial cell wall, and they play critical roles not only in maintaining biofilm formation but also in resisting environmental stress, including drug resistance. However, information regarding the mechanism mediating mycobacterial lipid synthesis remains limited. PatA is a membrane-associated acyltransferase and synthesizes phosphatidyl-<i>myo</i>-inositol mannosides (PIMs) in mycobacteria. Here, we found that PatA could regulate the synthesis of lipid ...[more]

PMID: 37212713

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