Intramacrophagic Mycobacterium avium bacilli are coated by a multiple lamellar structure: freeze fracture analysis of infected mouse liver

Rulong, Shen; Águas, Artur P.; Silva, P P da; Silva, M T

doi:10.1128/iai.59.11.3895-3902.1991

Cited by 46 publications

(20 citation statements)

References 30 publications

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“…p65 NF-B and MAPK activation has been clearly linked to engagement of TLRs, and M. avium is known to signal via TLR2. Furthermore, previous studies indicate a high level of GPL surface expression [31]. Together, the data suggest that GPLs could be one of the TLR2 ligands expressed by M. avium.…”

Section: Discussionsupporting

confidence: 68%

Glycopeptidolipids from Mycobacterium avium promote macrophage activation in a TLR2- and MyD88-dependent manner

Sweet

Schorey

2006

Journal of Leukocyte Biology

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The Toll-like receptors (TLRs) are key components in the immune response against numerous pathogens. Previous studies have indicated that TLR2 plays an essential role in promoting immune responses against mycobacterial infections. Prior work has also shown that mice deficient in TLR2 are more susceptible to infection by Mycobacterium tuberculosis, Mycobacterium bovis bacillus Calmette-Guerin, and Mycobacterium avium. Therefore, it is important to define the molecules expressed by pathogenic mycobacteria, which bind the various TLRs. Although a number of TLR agonists have been characterized for M. tuberculosis, no specific TLR ligand has been identified in M. avium. We have found that glycopeptidolipids (GPLs), which are highly expressed surface molecules on M. avium, can stimulate the nuclear factor-kappaB pathway as well as mitogen-activated protein kinase p38 and Jun N-terminal kinase activation and production of proinflammatory cytokines when added to murine bone marrow-derived macrophages. This stimulation was dependent on TLR2 and myeloid differentiation primary-response protein 88 (MyD88) but not TLR4. M. avium express apolar and serovar-specific (ss)GPLs, and it is the expression of the latter that determines the serotype of a particular M. avium strain. It is interesting that the ssGPLs activated macrophages in a TLR2- and MyD88-dependent manner, and no macrophage activation was observed when using apolar GPLs. ssGPLs also differed in their ability to activate macrophages with Serovars 1 and 2 stimulating inhibitor of kappaB p38 and phosphorylation and tumor necrosis factor alpha (TNF-alpha) secretion, while Serovar 4 failed to stimulate p38 activation and TNF-alpha production. Our studies indicate that ssGPLs can function as TLR2 agonists and promote macrophage activation in a MyD88-dependent pathway.

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Section: Discussionsupporting

confidence: 68%

Glycopeptidolipids from Mycobacterium avium promote macrophage activation in a TLR2- and MyD88-dependent manner

Sweet

Schorey

2006

Journal of Leukocyte Biology

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“…Some researchers have obtained results indicating that virulent strains of mycobacteria can escape the phagolysosomes and exist as viable bacteria in the cytoplasm of the macrophage [40,41], which would give the antigens access to the endogenous pathway of antigen processing [42]. These results, however, contrast with classical electron microscopy (EM) studies in which the mycobacteria were always found surrounded by a membrane structure [43], results recently confirmed by freeze fracture EM studies of infected mouse livers demonstrating a multi-lamellar coat between the phagosomal membrane and the bacterial cell wall [44,45]. In live infections, however, it is possible that even when contained in phagosomes, mycobacterial growth may damage the membrane, leading to leakage of antigens into the cytoplasm accessible for complexing with MHC class I [46].…”

Section: Immunity To Tuberculosismentioning

confidence: 99%

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

1997

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Andersen P. Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis. Scand J Immunol 1997;45:115-131 Tuberculosis (TB) is the largest single infectious cause of human mortality. The incidence of TB has remained high in most of the developing world and the disease has recently re-emerged as a public health problem in industrialized countries. The development of a new improved TB vaccine is a highly prioritized international research area, which has been further stimulated by the appearance of multi-drug resistant strains of Mycobacterium tuberculosis. The present status of the attempts to characterize the protective immune response to TB will be reviewed with special emphasis on recent progress in the identification and characterization of target molecules recognized by protective cells. This paper will focus on proteins released from live bacteria and discuss their role in the host-pathogen interaction and the ongoing attempts to use these molecules in TB subunit vaccines.

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“…4D, E) which shows either at the NH or Ha frequencies three additional plots typifying an Ile spin system [28] (Table 1). Starting from the amide proton resonance at 6 9.1 14, the corresponding Ha resonance was localized at 6 5.058, which in turn shows two cross-peaks at 3.349 ppm and 2.72 ppm. The absence of any further correlation was confirmed by the TOCSY spectrum which strictly exhibits the same pattern for this spin system in agreement with what is expected for a Phe residue.…”

Section: 'H-nmr and 'H-13c-nmr Cosy Analysis Of Lipopeptide-i One-dimentioning

confidence: 99%

A Unique Phenylalanine‐Containing Lipopeptide Isolated from a Rough‐Colony Variant of Mycobacterium Avium

Rivière

Puzo

Wright

et al. 1996

European Journal of Biochemistry

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Previous investigations have suggested that the biosynthesis of the Mycobacterium avium serovarspecific glycopeptidolipid antigens involves initial steps that include the participation of lipopeptides. The prevailing assumption is that subsequent glycosylation of those lipopeptides results in the fully glycosylated form of the glycopeptidolipid components. In an effort to identify potential precursors in the biosynthetic pathway of glycopeptidolipid components, we have identified a unique lipopeptide from an M. avium rough variant (MAC702) that was isolated from a patient suffering from a chronic M. avium lung infection. Upon examination it was revealed that although the total lipid extract from MAC702 lacked serovar-specific glycopeptidolipid antigens, it did contain a unique lipopeptide, possessing some amino acids identical to those found in the serovar-specific glycopeptidolipid antigens. Initial examination of acid-hydrolyzed samples of the lipopeptide (lipopeptide-I) revealed the presence of phenylalanine, alanine, and isoleucine, but no carbohydrate. Subsequent mass spectrometric and 'H-NMR and 'H-T-NMR correlation spectroscopy analysis confirmed the initial results and also revealed the presence of N-methylisoleucine. The following structure for lipopeptide-I was proposed: fatty acyl (C,9 or C,,)-Phe-N-methylIle-Ile-Phe-Ala-Ile-Ala-Phe. Lipopeptide-I is unlike any heretofore identified compound, however, it does have similar features to lipopeptides previously reported in mycobacteria and fungi. Although its structure does not verify that it is a direct precursor in glycopeptidolipid biosynthesis, the presence of certain components in lipopeptide-I indicate that it may share at least some pathways associated with the biosynthesis of the M. avium serovar-specific glycopeptidolipids.Keywords: Mycobacterium avium ; lipopeptide ; lipid ; cell envelope; AIDS.Increased concern for human immunodeficiency virus (HIV) infections has highlighted the need for effective antimicrobial therapy necessary to treat the opportunistic infections associated with that disease. Two mycobacterial agents that have emerged as important opportunistic pathogens in AIDS patients are Mycobacterium tuberculosis and Mycobacterium avium. Both remain important clinical issues primarily because of multipledrug resistance. By comparison, drug resistance in M. tuberculosis develops essentially as the result of inadequate or improper use of antimycobacterial drugs, which in turn gives rise to stepwise acquisition of mutated drug target genes [I, 21. Drug resistance in M. avium, however, is considered an inherent property of the wild-type organism [2], that results from the refractory nature of the organism's cell envelope. The current hypothesis is that multiple-drug resistance in M. avium is due to the presence of an exclusion barrier and the innate low permeability of the cell envelope [2]. It is therefore important to obtain a better understanding of the components that contribute to the complexity of the mycobacterial cell envelope.Base...

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Intramacrophagic Mycobacterium avium bacilli are coated by a multiple lamellar structure: freeze fracture analysis of infected mouse liver

Cited by 46 publications

References 30 publications

Glycopeptidolipids from Mycobacterium avium promote macrophage activation in a TLR2- and MyD88-dependent manner

Glycopeptidolipids from Mycobacterium avium promote macrophage activation in a TLR2- and MyD88-dependent manner

Host Responses and Antigens Involved in Protective Immunity to Mycobacterium tuberculosis

A Unique Phenylalanine‐Containing Lipopeptide Isolated from a Rough‐Colony Variant of Mycobacterium Avium

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