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Lipidomics and genomics of Mycobacterium tuberculosis reveal lineage-specific trends in mycolic acid biosynthesis

Portevin, Damien and Sukumar, Sudarkodi and Coscolla, Mireia and Shui, Guanghou and Li, Bowen and Guan, Xue Li and Bendt, Anne K. and Young, Douglas and Gagneux, Sebastien and Wenk, Markus R.. (2014) Lipidomics and genomics of Mycobacterium tuberculosis reveal lineage-specific trends in mycolic acid biosynthesis. MicrobiologyOpen, Vol. 3, H. 6. pp. 823-835.

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Official URL: http://edoc.unibas.ch/dok/A6329170

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Abstract

Mycolic acids (MAs) are α-alkyl, β-hydroxy long-chain fatty acids found in abundance in the cell envelope of the Mycobacterium tuberculosis complex (MTBC). MAs form an efficient permeability barrier, modulate host innate immune responses, and are the targets of several anti-tuberculosis drugs. Using mass spectrometry, we measured the relative abundance of 80 MA species across 36 clinical isolates of MTBC covering four major phylogenetic lineages. We found significant variations in the MA patterns between different MTBC strains and lineages. MA patterns of "ancient" lineages contrasted those from "modern" lineages, with a lower representation of alpha-mycolates among Lineage 6 strains and an inversion of the methoxy: keto-mycolates ratio in Lineage 1 strains. By interrogating the whole genome sequences of these MTBC strains, we identified relevant single-nucleotide polymorphisms that may sustain the lineage-specific MA patterns. Our results show that the strain genetic background influences MA metabolism and suggests that strain diversity should be considered in the development of new anti-tuberculosis drugs that target MA synthesis.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Portevin, Damien and Coscollá, Mireja and Guan, Xueli and Gagneux, Sebastien and Wenk, Markus
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Wiley]
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Sep 2015 14:32
Deposited On:06 Feb 2015 09:58

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