A specific secretion system mediates PPE41 transport in pathogenic mycobacteria

Abdallah M. Abdallah, Theo Verboom, Fredericke Hannes, Mohamad Safi, Michael Strong, David Eisenberg, René J.P. Musters, Christina M.J.E. Vandenbroucke-Grauls, Ben J. Appelmelk, Joen Luirink, Wilbert Bitter*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    177 Scopus citations

    Abstract

    Mycobacterial genomes contain two unique gene families, the so-called PE and PPE gene families, which are highly expanded in the pathogenic members of this genus. Here we report that one of the PPE proteins, i.e. PPE41, is secreted by pathogenic mycobacteria, both in culture and in infected macrophages. As PPE41 lacks a signal sequence a dedicated secretion system must be involved. A single gene was identified in Mycobacterium marinum that showed strongly reduced PPE41 secretion. This gene was located in a gene cluster whose predicted proteins encode components of an ESAT-6-like secretion system. This cluster, designated ESX-5, is conserved in various pathogenic mycobacteria, but not in the saprophytic species Mycobacterium smegmatis. Therefore, different regions of this cluster were introduced in M. smegmatis. Only introduction of the complete ESX-5 locus resulted in efficient secretion of heterologously expressed PPE41. This PPE secretion system is also involved in the virulence of pathogenic mycobacteria, as the ESX-5 mutant of M. marinum was affected in spreading to uninfected macrophages.

    Original languageEnglish (US)
    Pages (from-to)667-679
    Number of pages13
    JournalMolecular Microbiology
    Volume62
    Issue number3
    DOIs
    StatePublished - Nov 1 2006

    ASJC Scopus subject areas

    • Microbiology
    • Molecular Biology

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