The Envelope Layers of Mycobacteria with Reference to their Pathogenicity

Daffé, Mamadou; Draper, P.

doi:10.1016/s0065-2911(08)60016-8

Cited by 651 publications

(645 citation statements)

References 238 publications

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“…SP, secreted proteins. 1995; Barry et al, 1998;Daffe and Draper, 1998). The systematic identification and prominence of these proteins provides a solid basis for reconstructing the response networks involved in fatty acid degradation and lipid biosynthesis pathways that may reveal the mechanisms of Mtb persistence in its hosts (see Figure 6).…”

Section: The Cell Wallmentioning

confidence: 99%

Mycobacterium tuberculosisFunctional Network Analysis by Global Subcellular Protein Profiling

Mawuenyega

Forst

Dobos

et al. 2005

MBoC

204

184

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Trends in increased tuberculosis infection and a fatality rate of ϳ23% have necessitated the search for alternative biomarkers using newly developed postgenomic approaches. Here we provide a systematic analysis of Mycobacterium tuberculosis (Mtb) by directly profiling its gene products. This analysis combines high-throughput proteomics and computational approaches to elucidate the globally expressed complements of the three subcellular compartments (the cell wall, membrane, and cytosol) of Mtb. We report the identifications of 1044 proteins and their corresponding localizations in these compartments. Genome-based computational and metabolic pathways analyses were performed and integrated with proteomics data to reconstruct response networks. From the reconstructed response networks for fatty acid degradation and lipid biosynthesis pathways in Mtb, we identified proteins whose involvements in these pathways were not previously suspected. Furthermore, the subcellular localizations of these expressed proteins provide interesting insights into the compartmentalization of these pathways, which appear to traverse from cell wall to cytoplasm. Results of this large-scale subcellular proteome profile of Mtb have confirmed and validated the computational network hypothesis that functionally related proteins work together in larger organizational structures.

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Section: The Cell Wallmentioning

confidence: 99%

Mycobacterium tuberculosisFunctional Network Analysis by Global Subcellular Protein Profiling

Mawuenyega

Forst

Dobos

et al. 2005

MBoC

204

184

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“…Considering the extreme rigidity and impermeability of the outer permeability barrier [5] of M. tuberculosis, it is a paradox that liquid cultures contain excessive amounts of soluble proteins which are much larger than the small solutes referred to above and do not have the hydrophobic properties that would make them pass. To explain the presence of the large quantities and wide repertoire of proteins in the culture filtrates, it is necessary to suggest that there is a mechanism for protein transport across the outer permeability barrier, maybe some kind of a porin.…”

Section: The Envelope Of Mycobacteriamentioning

confidence: 99%

“…The mycobacterial cell wall in tissues is surrounded by a capsular polysaccharide coat which contains several proteins of bacterial origin and which is also part of a diffusion barrier that protects the bacilli against host defence mechanisms [5,6].…”

Section: The Envelope Of Mycobacteriamentioning

confidence: 99%

Liberation of Soluble Proteins from Live and Dead Mycobacterial Cells and the Implications for Pathogenicity of Tubercle Bacilli

Wiker¹

2001

Scand J Immunol

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Soluble proteins liberated from live M. tuberculosis are translocated through the cytoplasmic membrane to à periplasmic space'. For further export of proteins across the outer permeability barrier, it is necessary to postulate an excretion mechanism possibly involving some kind of porin. Observations of the repertoire of proteins in culture filtrates after liquid culture of M. tuberculosis show that a large repertoire of various kinds of proteins cross the outer permeability barrier of tubercle bacilli indicating that the excretion mechanism has a wide range of specificities for proteins. Culture filtrates of tubercle bacilli almost always contain both truly secreted proteins and cytoplasmatically-derived proteins. It is questionable whether cytoplasmic proteins can cross an intact cytoplasmic membrane. The simplest explanation for the appearance of cytoplasmic proteins in culture filtrates of tubercle bacilli would be that they are released after disintegration of the cytoplasmic membrane in dying or dead bacilli. Tubercle bacilli armed with secreted factors that may specifically inhibit innate and adaptive immune responses, excrete these from the periplasmic space of live bacilli. Unspecific in its character, the excretion mechanism also liberates proteins that are essential for building and maintaining the cell wall, thereby reducing the effectiveness of this process. This may be part of the explanation why M. tuberculosis and other pathogenic mycobacteria grow so slowly. Finally, it may be postulated that dormant or latent tubercle bacilli use their repertoire of secreted proteins to control their intracellular habitat and that bacterial cytoplasmic proteins would not be liberated from such bacilli. The consequence would be that only immune responses to secreted proteins would be effective for elimination of the dormant stage of infection. In a situation with active infection there will be considerable growth and turnover of bacilli with liberation of all kinds of immunogenic substances from the bacilli. In this situation immunity against cytoplasmic proteins would also be effective and immunity to cytoplasmic proteins should also be effective for control of the reactivation of latent disease because as soon as the bacilli start to grow there will also be a subpopulation of dead bacilli on the arena. THE ENVELOPE OF MYCOBACTERIACompared to many other bacterial genera, the outer permeability barrier of mycobacteria is extremely tight and particularly so for M. tuberculosis [1,2]. This is owing to the unusual structure of the mycobacterial cell wall which is highly impermeable to hydrophilic solutes. Hydrophobic solutes can penetrate the barrier [1]. Antibiotics of the most hydrophobic types for example, are also the most effective drugs against mycobacteria [3,4].Considering the extreme rigidity and impermeability of the outer permeability barrier [5] of M. tuberculosis, it is a paradox that liquid cultures contain excessive amounts of soluble proteins which are much larger than the small solutes referred to...

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“…The highly complex mycobacterial cell wall envelope plays essential roles in controlling the growth of the bacteria, its survival in the infected host, and the immunologic response [9,12,15]. Our present day understanding of its structure reveals a three-compartment entity composed of a plasma membrane; the cell wall core; and the extractable noncovalently linked glycans, lipids, and proteins (Fig.…”

Section: Introductionmentioning

confidence: 99%

Organization of the mycobacterial cell wall: a nanoscale view

Alsteens

Verbelen

Dague

et al. 2007

Pflugers Arch - Eur J Physiol

109

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The biosynthesis of the Mycobacterium tuberculosis cell wall is targeted by some of the most powerful antituberculous drugs. To date, the molecular mechanisms by which these antibiotics affect the cell wall characteristics are not well understood. Here, we used atomic force microscopy -in three different modes -to probe the nanoscale surface properties of live mycobacteria and their modifications upon incubation with four antimycobacterial drugs: isoniazid, ethionamide, ethambutol, and streptomycine. Topographic imaging, combined with quantitative surface roughness analysis, demonstrated that all drugs induce a substantial increase of surface roughness to an extent that correlates with the localization of the target (i.e., synthesis of mycolic acids, arabinogalactans, or proteins). Chemical force microscopy with hydrophobic tips revealed that the structural alterations induced by isoniazid and ethambutol were correlated with a dramatic decrease of cell surface hydrophobicity, reflecting the removal of the outermost mycolic acid layer. Consistent with this finding, tapping mode imaging, combined with immunogold labeling, showed that the two drugs lead to the massive exposure of hydrophilic lipoarabinomannans at the surface. Taken together, these structural, chemical, and immunological data provide novel insight into the action mode of antimycobacterial drugs, as well as into the spatial organization of the mycobacterial cell wall.

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The Envelope Layers of Mycobacteria with Reference to their Pathogenicity

Cited by 651 publications

References 238 publications

Mycobacterium tuberculosisFunctional Network Analysis by Global Subcellular Protein Profiling

Mycobacterium tuberculosisFunctional Network Analysis by Global Subcellular Protein Profiling

Liberation of Soluble Proteins from Live and Dead Mycobacterial Cells and the Implications for Pathogenicity of Tubercle Bacilli

Organization of the mycobacterial cell wall: a nanoscale view

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