title: Lipidomics and genomics of Mycobacterium tuberculosis reveal lineage-specific trends in mycolic acid biosynthesis.
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.
authors.affiliation: Mycobacterial Division Research, NIMR, MRC, NW71AA, London, United Kingdom; Department of Medical Parasitology and Infection Biology, Swiss TPH, 4002, Basel, Switzerland; University of Basel, 4002, Basel, Switzerland.
authors.forename: Damien
authors.initials: D
authors.lastname: Portevin
authors.forename: Sudarkodi
authors.initials: S
authors.lastname: Sukumar
authors.forename: Mireia
authors.initials: M
authors.lastname: Coscolla
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Bowen
authors.initials: B
authors.lastname: Li
authors.forename: Xue Li
authors.initials: XL
authors.lastname: Guan
authors.forename: Anne K
authors.initials: AK
authors.lastname: Bendt
authors.forename: Douglas
authors.initials: D
authors.lastname: Young
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
mesh_terms: D016680:Genome, Bacterial; D023281:Genomics; D006801:Humans; D013058:Mass Spectrometry; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D009171:Mycolic Acids / Q000737:chemistry / Q000378:metabolism*; D010802:Phylogeny; D013045:Species Specificity; D014376:Tuberculosis / Q000382:microbiology*
chemical_list: D009171:Mycolic Acids
keywords: Genomics; lipidomics; mycolic acid; phylogenetics; tuberculosis