Lipids of Pathogenic Mycobacteria: Contributions to Virulence and Host Immune Suppression

Institut Pasteur, Unité Postulante Pathogénomique Mycobactérienne Intégrée, Paris, France.
Transboundary and Emerging Diseases (Impact Factor: 2.94). 06/2009; 56(6-7):255-68. DOI: 10.1111/j.1865-1682.2009.01072.x
Source: PubMed


Mycobacteria are characterized by a complex cell wall, the lipid nature of which confers to the bacilli resistance to drying, acid or alkaline conditions, and to chemical disinfectants and therapeutic agents. Pathogenic species, such as Mycobacterium tuberculosis, M. leprae and M. ulcerans, have evolved various strategies to establish residence in their hosts and provoke long-term infections. There is mounting evidence that the unique lipids composing their envelopes, strategically located at the host-pathogen interface, contribute to their escape from immune surveillance. Here, the chemical structure, host cell receptors and biological actions of this emerging class of mycobacterial virulence factors are reviewed.

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Available from: Caroline Demangel, Apr 18, 2014
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    • "PGLs are only produced by the members of the MTBC and related slow-growing mycobacteria, yet even among the mycobacteria that make PGL; there are species-specific modifications in the carbohydrate moiety [Daffe and Laneelle, 1988; Onwueme et al., 2005; schematically illustrated in (Veyrier et al., 2011)]. The PGLs have been implicated in mycobacterial pathogenicity such as oxidative stress resistance (Chan et al., 1989), cell tropism (Ng et al., 2000; Rambukkana, 2001), and immunomodulation (Reed et al., 2004; Guenin-Mace et al., 2009; Cambier et al., 2014). "
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    ABSTRACT: The genus Mycobacterium is comprised of more than 150 species that reside in a wide variety of habitats. Most mycobacteria are environmental organisms that are either not associated with disease or are opportunistic pathogens that cause non-transmissible disease in immunocompromised individuals. In contrast, a small number of species, such as the tubercle bacillus, Mycobacterium tuberculosis, are host-adapted pathogens for which there is no known environmental reservoir. In recent years, gene disruption studies using the host-adapted pathogen have uncovered a number of "virulence factors," yet genomic data indicate that many of these elements are present in non-pathogenic mycobacteria. This suggests that much of the genetic make-up that enables virulence in the host-adapted pathogen is already present in environmental members of the genus. In addition to these generic factors, we hypothesize that molecules elaborated exclusively by professional pathogens may be particularly implicated in the ability of M. tuberculosis to infect, persist, and cause transmissible pathology in its host species, Homo sapiens. One approach to identify these molecules is to employ comparative analysis of mycobacterial genomes, to define evolutionary events such as horizontal gene transfer (HGT) that contributed M. tuberculosis-specific genetic elements. Independent studies have now revealed the presence of HGT genes in the M. tuberculosis genome and their role in the pathogenesis of disease is the subject of ongoing investigations. Here we review these studies, focusing on the hypothesized role played by HGT loci in the emergence of M. tuberculosis from a related environmental species into a highly specialized human-adapted pathogen.
    Full-text · Article · Apr 2014 · Frontiers in Microbiology
    • "[4]. The complex cell wall of mycobacteria contains unusual lipids that are essential for survival and virulence [5] [6]. In addition, the cytosol of mycobacteria contains organites (lipid inclusion bodies) that store important lipids [triacylglycerol (TAG)] for long-term survival during the dormancy phase [7]. "
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    ABSTRACT: The mycobacterial Rv3097c-encoded lipase LipY is considered as a true lipase involved in the hydrolysis of triacylglycerol stored in lipid inclusion bodies for the survival of dormant mycobacteria. To date, orlistat is the only known LipY inhibitor. In view of the important emerging role of this enzyme, a search for small-molecule inhibitors of LipY was made, leading to the identification of some new compounds (8a-8d, 8f, 8h and 8i) with potent inhibitory activities against recombinant LipY, with no cytotoxicity [50% inhibitory concentration (CC50) ≥500μg/mL]. The compounds 6a, 8c and 8f potently inhibited (>90%) the growth of Mycobacterium tuberculosis H37Rv grown under hypoxia (oxygen-depleted condition) but had no effect on aerobically grown bacilli, suggesting that these new small molecules are highly selective towards the growth inhibition of hypoxic cultures of M. tuberculosis and hence provide new leads for combating latent tuberculosis.
    No preview · Article · May 2013 · International journal of antimicrobial agents
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    • "e unique lipids composing the cell envelope of pathogenic mycobacteria such as lipoarabinomannan (LAM), lipomannan (LM), phosphatidylinositol mannoside (PIM), and trehalose 6,6 ′ -dimycolate (TDM) interact with membrane CD14 (mCD14) and TLR2 on macrophages and activate signaling pathways inducing the innate immune response to infection [6] [7] [11] [12]. A soluble form of plasma CD14 (sCD14) is known to sensitize host cells to LPS; however, it also interacts with mycobacterial LAM causing upregulated endogenous CD14 gene expression [13]. "
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    ABSTRACT: The mechanisms that promote either resistance or susceptibility to TB disease remain insufficiently understood. Our aim was to compare the expression of cell signaling transduction receptors, CD14, TLR2, CD206, and β2 integrin LFA-1 on monocytes from patients with active TB or nonmycobacterial lung disease and healthy individuals with M.tb latency and uninfected controls to explain the background of the differences between clinical and subclinical forms of M.tb infection. A simultaneous increase in the expression of the membrane bound mCD14 receptor and LFA-1 integrin in patients with active TB may be considered a prodrome of breaking immune control by M.tb bacilli in subjects with the latent TB and absence of clinical symptoms.
    Full-text · Article · Jan 2013 · Clinical and Developmental Immunology
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