title: Mycobacterium tuberculosis proteins involved in mycolic acid synthesis and transport localize dynamically to the old growing pole and septum.
abstract: Understanding the mechanism that controls space-time coordination of elongation and division of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is critical for fighting the tubercle bacillus. Most of the numerous enzymes involved in the synthesis of Mycolic acid - Arabinogalactan-Peptidoglycan complex (MAPc) in the cell wall are essential in vivo. Using a dynamic approach, we localized Mtb enzymes belonging to the fatty acid synthase-II (FAS-II) complexes and involved in mycolic acid (MA) biosynthesis in a mycobacterial model of Mtb: M. smegmatis. Results also showed that the MA transporter MmpL3 was present in the mycobacterial envelope and was specifically and dynamically accumulated at the poles and septa during bacterial growth. This localization was due to its C-terminal domain. Moreover, the FAS-II enzymes were co-localized at the poles and septum with Wag31, the protein responsible for the polar localization of mycobacterial peptidoglycan biosynthesis. The dynamic localization of FAS-II and of the MA transporter with Wag31, at the old-growing poles and at the septum suggests that the main components of the mycomembrane may potentially be synthesized at these precise foci. This finding highlights a major difference between mycobacteria and other rod-shaped bacteria studied to date. Based on the already known polar activities of envelope biosynthesis in mycobacteria, we propose the existence of complex polar machinery devoted to the biogenesis of the entire envelope. As a result, the mycobacterial pole would represent the Achilles' heel of the bacillus at all its growing stages.
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Carel
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Kanjana
authors.initials: K
authors.lastname: Nukdee
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Cantaloube
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bonne
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Cheikh T
authors.initials: CT
authors.lastname: Diagne
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Laval
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Daffé
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Zerbib
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology*; D054889:Fatty Acid Synthase, Type II / Q000378:metabolism; D005685:Galactans / Q000378:metabolism; D055786:Gene Knockout Techniques; D049452:Green Fluorescent Proteins; D018715:Microscopy, Video; D015394:Molecular Structure; D046912:Multiprotein Complexes / Q000096:biosynthesis* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D009171:Mycolic Acids / Q000378:metabolism*; D010457:Peptidoglycan / Q000378:metabolism; D064047:Spindle Poles / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D005685:Galactans; D046912:Multiprotein Complexes; D009171:Mycolic Acids; D010457:Peptidoglycan; C000591547:Wag31 protein, Mycobacterium tuberculosis; D049452:Green Fluorescent Proteins; D054889:Fatty Acid Synthase, Type II; C005653:arabinogalactan