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  • The EMBO Journal (2006) 25, 1436 - 1444
  • doi:10.1038/sj.emboj.7601048

Published online: 16 March 2006

LppX is a lipoprotein required for the translocation of phthiocerol dimycocerosates to the surface of Mycobacterium tuberculosis

Gerlind Sulzenbacher1, Stéphane Canaan1,4, Yann Bordat2, Olivier Neyrolles2, Gustavo Stadthagen2, Véronique Roig-Zamboni1, Jean Rauzier2, Damien Maurin1,a, Françoise Laval3, Mamadou Daffé3, Christian Cambillau1, Brigitte Gicquel2, Yves Bourne1 and Mary Jackson2

  1. AFMB, CNRS UMR 6098, Marseille Cedex, France
  2. Unité de Génétique Mycobactérienne, Institut Pasteur, Paris Cedex, France
  3. Département 'Mécanismes Moléculaires des Infections Mycobactériennes', Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, Université Paul Sabatier, Toulouse Cedex, France
  4. Laboratoire d'Enzymologie Interfaciale et de Physiologie de la Lipolyse CNRS UPR 9025, Marseille Cedex, France

Correspondence to:

Mary Jackson, Unité de Génétique Mycobactérienne, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Tel.: +33 1 45 68 88 77; Fax: +33 1 45 68 88 43; E-mail: mjackson@pasteur.fr

Yves Bourne, AFMB, CNRS UMR 6098, Case 932 Campus de Luminy, 163 Avenue de Luminy, 13288 Marseille Cedex 09, France. Tel.: +33 4 91 82 55 66; Fax: +33 4 91 26 67 20; E-mail: yves.bourne@afmb.univ-mrs.fr

aPresent address: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB23EH, UK

Received 16 August 2005; Accepted 20 February 2006

Cell envelope lipids play an important role in the pathogenicity of mycobacteria, but the mechanisms by which they are transported to the outer membrane of these prokaryotes are largely unknown. Here, we provide evidence that LppX is a lipoprotein required for the translocation of complex lipids, the phthiocerol dimycocerosates (DIM), to the outer membrane of Mycobacterium tuberculosis. Abolition of DIM transport following disruption of the lppX gene is accompanied by an important attenuation of the virulence of the tubercle bacillus. The crystal structure of LppX unveils an U-shaped beta-half-barrel dominated by a large hydrophobic cavity suitable to accommodate a single DIM molecule. LppX shares a similar fold with the periplasmic molecular chaperone LolA and the outer membrane lipoprotein LolB, which are involved in the localization of lipoproteins to the outer membrane of Gram-negative bacteria. Based on the structure and although an indirect participation of LppX in DIM transport cannot yet be ruled out, we propose LppX to be the first characterized member of a family of structurally related lipoproteins that carry lipophilic molecules across the mycobacterial cell envelope.

  • Keywords:

    • crystallography,
    • lipoprotein,
    • Mycobacterium,
    • phthiocerol dimycocerosates,
    • tuberculosis