<i>Mycobacterium tuberculosis</i>cell envelope lipids and the host immune response

Karakousis, Petros C.; Bishai, William R.; Dorman, Susan E.

doi:10.1046/j.1462-5822.2003.00351.x

Cited by 130 publications

(109 citation statements)

References 129 publications

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“…Many lipid species expressed by M. tuberculosis can be presented by CD1a, CD1b, and CD1c, including MA, lipoglycans (such as LAM) and PIMs, lipopeptides, mannosyl-β-1-phosphomycoketides, and sulpholipids 60 . Other cell wall lipids that have been described as activating/modulating the immune response include PDIM, DAT, and polyacyltrehalose (PAT) 61 .…”

Section: Mycobacterial Lipids During Transition To the Chronic Phase mentioning

confidence: 99%

Bacterial immunostat: Mycobacterium tuberculosis lipids and their role in the host immune response

Queiroz

Riley

2017

Rev. Soc. Bras. Med. Trop.

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The lipid-rich cell wall of Mycobacterium tuberculosis is a dynamic structure that is involved in the regulation of the transport of nutrients, toxic host-cell effector molecules, and anti-tuberculosis drugs. It is therefore postulated to contribute to the longterm bacterial survival in an infected human host. Accumulating evidence suggests that M. tuberculosis remodels the lipid composition of the cell wall as an adaptive mechanism against host-imposed stress. Some of these lipid species (trehalose dimycolate, diacylated sulphoglycolipid, and mannan-based lipoglycans) trigger an immunopathologic response, whereas others (phthiocerol dimycocerosate, mycolic acids, sulpholipid-1, and di-and polyacyltrehalose) appear to dampen the immune responses. These lipids appear to be coordinately expressed in the cell wall of M. tuberculosis during different phases of infection, ultimately determining the clinical fate of the infection. This review summarizes the current state of knowledge on the metabolism, transport, and homeostatic or immunostatic regulation of the cell wall lipids, and their orchestrated interaction with host immune responses that results in bacterial clearance, persistence, or tuberculosis.

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Section: Mycobacterial Lipids During Transition To the Chronic Phase mentioning

confidence: 99%

Bacterial immunostat: Mycobacterium tuberculosis lipids and their role in the host immune response

Queiroz

Riley

2017

Rev. Soc. Bras. Med. Trop.

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“…The mycobacterial cell envelope is rich in glycolipids containing trehalose as a sugar moiety, such as TMM, TDM, di-, tri, and pentaacyltrehalose, or sulfolipid, some of which play an important role in virulence and possess potent immunomodulatory properties (24,25). We therefore asked whether the presence of free trehalose might interfere with biosynthesis of trehalose-containing Mtb glycolipids, as alterations in the lipid profile could have contributed to the observed attenuation of the transporter mutants in mice.…”

Section: Impaired Trehalose Recycling Does Not Alter the Glycolipid Pmentioning

confidence: 99%

Trehalose-recycling ABC transporter LpqY-SugA-SugB-SugC is essential for virulence of Mycobacterium tuberculosis

Kalscheuer

Weinrick

Usha

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

170

245

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Mycobacterium tuberculosis (Mtb) is an exclusively human pathogen that proliferates within phagosomes of host phagocytes. Host lipids are believed to provide the major carbon and energy sources for Mtb, with only limited availability of carbohydrates. There is an apparent paradox because five putative carbohydrate uptake permeases are present in Mtb, but there are essentially no host carbohydrates inside phagosomes. Nevertheless, carbohydrate transporters have been implicated in Mtb pathogenesis, suggesting that acquisition of host sugars is important during some stages of infection. Here we show, however, that the LpqY-SugA-SugB-SugC ATP-binding cassette transporter is highly specific for uptake of the disaccharide trehalose, a sugar not present in mammals, thus refuting a role in nutrient acquisition from the host. Trehalose release is known to occur as a byproduct of the biosynthesis of the mycolic acid cell envelope by Mtb's antigen 85 complex. The antigen 85 complex constitutes a group of extracellular mycolyl transferases, which transfer the lipid moiety of the glycolipid trehalose monomycolate (TMM) to arabinogalactan or another molecule of TMM, yielding trehalose dimycolate. These reactions also lead to the concomitant extracellular release of the trehalose moiety of TMM. We found that the LpqY-SugA-SugB-SugC ATP-binding cassette transporter is a recycling system mediating the retrograde transport of released trehalose. Perturbations in trehalose recycling strongly impaired virulence of Mtb. This study reveals an unexpected accessory component involved in the formation of the mycolic acid cell envelope in mycobacteria and provides a previously unknown role for sugar transporters in bacterial pathogenesis. microbial pathogenesis | mycolic acid biosynthesis | cell wall formation | carbon metabolism T uberculosis, caused by the bacterium Mycobacterium tuberculosis (Mtb), remains a major threat to global health, claiming the life of two million individuals each year (1). Mtb is an obligate human pathogen predominantly growing intracellularly within phagosomes of host phagocytes, although other cell types and niches might also be occupied during different phases of infection. Notwithstanding, there is strong evidence that host lipids provide the main carbon and energy sources for Mtb during infection, with carbohydrates being largely inaccessible for the bacilli (2-5). Support for this, among further findings, comes from the observed up-regulation of lipid catabolism genes of Mtb during intracellular replication in macrophages (4) and from the joint essentiality of the two isocitrate lyase isoforms, icl1 and icl2, for growth of Mtb in mice (6). It has to be mentioned that the importance of some lipid catabolic pathways for in vivo carbon metabolism of Mtb may be somewhat overestimated, as attenuation of mutants might be caused by accumulation of toxic intermediates of incomplete metabolism rather than by blocked utilization of a substrate (7). Nevertheless, the published literature strongly suggests that Mtb ...

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“…The lipid-rich cell walls of mycobacteria have proven to be an important defence mechanism aiding their survival within the host. Trehalose mycolates (Geisel et al, 2005) and various other lipids, such as the mannose-capped lipoarabinomannan, phthiocerol dimycocerosate, and the 19-kDa lipoprotein, have all been identified as potential contributors to the pathogenesis of mycobacterial infection (Karakousis et al, 2004). In fact, pharmaceuticals used to successfully treat tuberculosis, such as isoniazid, ethionamide and pyrazinamide, do so by inhibiting mycolic acid or fatty acid synthesis, thereby altering cell-wall virulence (Schroeder et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…The lipid-rich cell wall of M. tuberculosis contains several factors that contribute to its survival within the host (Karakousis et al, 2004). Trehalose 6,69-dimycolate (TDM), a glycolipid located in the mycobacterial cell wall, is an important component of this defence mechanism.…”

Section: Introductionmentioning

confidence: 99%

CD3+ cells transfer the hypersensitive granulomatous response to mycobacterial glycolipid trehalose 6,6′-dimycolate in mice

Guidry

Hunter²,

Actor

2006

Microbiology

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The granulomatous response is the characteristic histological feature of Mycobacterium tuberculosis infection that is essential for organism containment. Trehalose 6,6-dimycolate (TDM), a cell-wall glycolipid present on most mycobacterial species, has been implicated in the pathogenesis of M. tuberculosis infection. TDM has potent immunoregulatory and inflammatory properties, and can be used to model granulomatous reactions that mimic, in part, pathology caused during active infection. This study examined the hypersensitive granulomatous response, focusing on cellular responses specific to TDM. Lungs from mice immunized with TDM emulsion demonstrated exacerbated histological damage, inflammation, and lymphocytic infiltration upon subsequent challenge with TDM. Splenocytes recovered from these mice demonstrated significant interferon (IFN)-γ production during recall response to TDM, as well as increased production of proinflammatory mediators (tumour necrosis factor-α, interleukin-6 and macrophage inflammatory protein-1α). The exacerbated response could be adoptively transferred to naïve mice. Administration of non-adherent lymphocytes or purified CD3+ cells from TDM-immunized mice led to increased inflammation, lymphocytic infiltration, and vascular endothelial cell damage upon challenge with TDM. Recipient mice that received immunized CD3+ lymphocytes demonstrated significant increases in Th1-type cytokines and proinflammatory mediators in lung tissue following TDM challenge. When CD1d−/− mice were immunized with TDM, they failed to generate a specific IFN-γ response, suggesting a role for this molecule in the generation of hypersensitivity. These experiments provide further evidence for the involvement of TDM-specific CD3+ T cells in pathological damage elicited during M. tuberculosis infection.

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Mycobacterium tuberculosiscell envelope lipids and the host immune response

Cited by 130 publications

References 129 publications

Bacterial immunostat: Mycobacterium tuberculosis lipids and their role in the host immune response

Bacterial immunostat: Mycobacterium tuberculosis lipids and their role in the host immune response

Trehalose-recycling ABC transporter LpqY-SugA-SugB-SugC is essential for virulence of Mycobacterium tuberculosis

CD3+ cells transfer the hypersensitive granulomatous response to mycobacterial glycolipid trehalose 6,6′-dimycolate in mice

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