title: Mycolic acids: deciphering and targeting the Achilles' heel of the tubercle bacillus.
abstract: Mycolic acids are unique long chain fatty acids found in the lipid-rich cell walls of mycobacteria including the tubercle bacillus Mycobacterium tuberculosis. Essential for viability and virulence, enzymes involved in the biosynthesis of mycolic acids represent novel targets for drug development. This is particularly relevant to the impact on global health given the rise of multidrug resistant and extensively drug resistant strains of M. tuberculosis. In this review, we discuss recent advances in our understanding of how mycolic acid are synthesised, especially the potential role of specialised fatty acid synthase complexes. Also, we examine the role of a recently reported mycolic acid transporter MmpL3 with reference to several reports of the targeting of this transporter by diverse compounds with anti-M. tuberculosis activity. Additionally, we consider recent findings that place mycolic acid biosynthesis in the context of the cell biology of the bacterium, viz its localisation and co-ordination with the bacterial cytoskeleton, and its role beyond maintaining cell envelope integrity.
authors.affiliation: School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Vijayashankar
authors.initials: V
authors.lastname: Nataraj
authors.affiliation: School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Cristian
authors.initials: C
authors.lastname: Varela
authors.affiliation: School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Asma
authors.initials: A
authors.lastname: Javid
authors.affiliation: School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Albel
authors.initials: A
authors.lastname: Singh
authors.affiliation: School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.affiliation: School of Biosciences and Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: Apoorva
authors.initials: A
authors.lastname: Bhatt
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D055808:Drug Discovery; D064429:Fatty Acid Synthases / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000201:enzymology / Q000378:metabolism* / Q000472:pathogenicity; D009171:Mycolic Acids / Q000737:chemistry / Q000378:metabolism*; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology; D014774:Virulence
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C000599913:MmpL3 protein, Mycobacterium tuberculosis; D009171:Mycolic Acids; D064429:Fatty Acid Synthases