基于非靶向脂质组学分析脂蛋白Rv1411c对结核分枝杆菌脂质代谢的影响OA北大核心CSTPCD

Objective:To explore the effects of lipoprotein Rv1411c on Mycobacterium tuberculosis(MTB)lipid metabolism based on non-targeted lipomics.Methods:The H37Rv-Rv1411c gene knocked-out strain(△Rv1411c)was constructed and its optical density values(A600)was measured and growth curve was drawn to be compared with that of the MTB standard strain(H37Rv).The lipid compositions of the two strains were extracted from the culture supernatant and were further analyzed using liquid chromatography-mass spectrometry technology(LC-MS)and non-targeted lipomics analysis platform.Partial leastsquares discriminant analysis(PLS-DA)and Kyoto Encylopaedia of Genes and Genomes(KEGG)enrichment analysis were used to explore metabolic product differences and pathways between the two groups.Results:Based on the LC-MS analysis,460 lipid metabolites which belonged to 28 classes were identified.Then 158 lipid metabolites belonged to 17 classes with variable importance in projection(VIP)＞1 were further selected based on PLS-DA model.Using the fold change(FC)＞1.5 or＜0.67 and P＜0.05 as screening criteria,36 lipids with significant difference were confirmed.Among them,12 lipids were upregulated and 24 lipids were downregulated.KEGG pathway analysis suggested that the differentiating metabolites were mainly involved in eight metabolic pathways:glycerophospholipid metabolism pathway,linolenic acid-metabolism pathway,alpha-linolenic acid metabolism pathway,glycosylphosphatidylinositol(GPI)-anchor biosynthesis pathway,glycerolipid metabolism pathway,sphingolipid metabolism pathway,arachidonic acid metabolism pathway and biosynthesis of unsaturated fatty acids pathway.Glycerophospholipid metabolism pathway had the highest impact factor,followed by glycerolipid metabolism and glycosylphosphatidylinositol(GPI)-anchor biosynthesis pathway.Conclusion:Lipoprotein Rv1411c can significantly affect the lipid metabolism of MTB and may participate in the regulation of MTB lipid metabolism.