Comparative metabolic profiling of mce1 operon mutant vs wild-type Mycobacterium tuberculosis strains

Pathogens and Disease
Adriano QueirozLee W Riley

Abstract

Mycobacterium tuberculosis disrupted in a 13-gene operon (mce1) accumulates free mycolic acids (FM) in its cell wall and causes accelerated death in mice. Here, to more comprehensively analyze differences in their cell wall lipid composition, we used an untargeted metabolomics approach to compare the lipid profiles of wild-type and mce1 operon mutant strains. By liquid chromatography-mass spectrometry, we identified >400 distinct lipids significantly altered in the mce1 mutant compared to wild type. These lipids included decreased levels of saccharolipids and glycerophospholipids, and increased levels of alpha-, methoxy- and keto mycolic acids (MA), and hydroxyphthioceranic acid. The mutant showed reduced expression of mmpL8, mmpL10, stf0, pks2 and papA2 genes involved in transport and metabolism of lipids recognized to induce proinflammatory response; these lipids were found to be decreased in the mutant. In contrast, the transcripts of mmpL3, fasI, kasA, kasB, acpM and RV3451 involved in MA transport and metabolism increased; MA inhibits inflammatory response in macrophages. Since the mce1 operon is known to be regulated in intracellular M. tuberculosis, we speculate that the differences we observed in cell wall lipid metabol...Continue Reading

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Citations

Oct 30, 2016·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Diana A Aguilar-AyalaJorge A Gonzalez-Y-Merchand
Mar 23, 2017·Revista Da Sociedade Brasileira De Medicina Tropical·Adriano Queiroz, Lee W Riley
May 3, 2018·Pathogens and Disease·Kaley M WilburnBrian C VanderVen
Sep 26, 2020·Frontiers in Immunology·Jéssica D PetrilliAdriano Queiroz
Feb 6, 2021·Metabolites·Dorothy Pei Shan Chang, Xue Li Guan
Feb 21, 2021·Current Opinion in Microbiology·Katherine A Abrahams, Gurdyal S Besra

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