Anti‐Cord Factor (Trehalose 6,6′‐Dimycolate) IgG Antibody in Tuberculosis Patients Recognizes Mycolic Acid Subclasses

Pan, Jiongwei; Fujiwara, Nagatoshi; Oka, Shiro; Maekura, Ryoji; Ogura, Takeshi; Yano, Ikuya

doi:10.1111/j.1348-0421.1999.tb01221.x

Cited by 54 publications

(32 citation statements)

References 27 publications

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“…Later studies using a different immunization method (emulsified pure antigen rather than carrier protein-conjugated antigen) and more sensitive detection systems revealed that antisera against either M. tuberculosis or M. avium cord factor raised in rabbits preferentially recognized TOM from the species used as antigen source (21,22), suggesting that the underlying IgG antibodies were directed not against the carbohydrate backbone but against mycolic acids as the molecular components conferring species specificity. These results could subsequently be confirmed with sera of human patients infected with M. tuberculosis or M. avium: the patient sera were primarily reactive against cord factor of the infecting mycobacterial species, which independently had been determined bacteriologically (69).…”

Section: Humoral Responsesupporting

confidence: 63%

Immunological Properties of Trehalose Dimycolate (Cord Factor) and Other Mycotic Acid‐Containing Glycolipids–‐A Review

Ryll

Kumazawa

Yano

2001

Microbiology and Immunology

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142

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Mycolic acids are characteristic fatty acids of Mycobacteria and are responsible for the wax-like consistence of these microorganisms. Decades of research revealed that mycolic acid-containing g1ycolipids, in particular trehalose-6,6'-dimycolate (TDM, cord factor) as their best-studied representative, exert a number of immunomodifying effects. They are able to stimulate innate, early adaptive and both humoral and cellular adaptive immunity. Most functions can be associated with their ability to induce a wide range of chemokines (MCP-t, MIP-ta, IL-8) and cytokines (e.g., IL-12, IFN-y, TNF-a, IL-4, IL-6, IL-tO). This review tries to link well-known properties of mycolic acid-containing glycolipids, e.g., stimulation of cellular and humoral immunity, granuloma formation and anti-tumor activity, with recent findings in molecular immunology and to give an outlook on potential practical applications.

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Section: Humoral Responsesupporting

confidence: 63%

Immunological Properties of Trehalose Dimycolate (Cord Factor) and Other Mycotic Acid‐Containing Glycolipids–‐A Review

Ryll

Kumazawa

Yano

2001

Microbiology and Immunology

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142

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“…Recently, mycoloyl glycolipids have been reported to be a unique lipid antigen restricted by the CD-1 antigen presentation molecule (Beckman et al, 1994;Moody et al, 1997Moody et al, , 1999Niazi et al, 2001). Furthermore, it has been found that human patient sera (IgG) against TDM from either M. tuberculosis or the Mycobacterium aviumintracellulare group recognized each respective TDM from the species used as the antigen source (Enomoto et al, 1998;Pan et al, 1999), suggesting that the underlying IgG antibodies were directed not against the carbohydrate backbone, but against the mycolic acid moiety. Therefore, determination of the precise molecular structure of TDM is essential, particularly focussing on the mycolic acid moiety.…”

Section: Introductionmentioning

confidence: 99%

Intact molecular characterization of cord factor (trehalose 6,6′-dimycolate) from nine species of mycobacteria by MALDI-TOF mass spectrometry

et al. 2005

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Cord factor (trehalose 6,69-dimycolate, TDM) is an unique glycolipid with a trehalose and two molecules of mycolic acids in the mycobacterial cell envelope. Since TDM consists of two molecules of very long branched-chain 3-hydroxy fatty acids, the molecular mass ranges widely and in a complex manner. To characterize the molecular structure of TDM precisely and simply, an attempt was made to determine the mycolic acid subclasses of TDM and the molecular species composition of intact TDM by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for the first time. The results showed that less than 1 mg mycolic acid methyl ester of TDM from nine representative species of mycobacteria and TDM from the same species was sufficient to obtain well-resolved mass spectra composed of pseudomolecular ions [M+Na] + . Although the mass ion distribution was extremely diverse, the molecular species of each TDM was identified clearly by constructing a molecular ion matrix consisting of the combination of two molecules of mycolic acids. The results showed a marked difference in the molecular structure of TDM among mycobacterial species and subspecies. TDM from Mycobacterium tuberculosis (H 37 Rv and Aoyama B) showed a distinctive mass pattern and consisted of over 60 molecular ions with a-, methoxy-and ketomycolate. TDM from Mycobacterium bovis BCG Tokyo 172 similarly showed over 35 molecular ions, but that from M. bovis BCG Connaught showed simpler molecular ion clusters consisting of less than 35 molecular species due to a complete lack of methoxymycolate. Mass ions due to TDM from M. bovis BCG Connaught and Mycobacterium kansasii showed a biphasic distribution, but the two major peaks of TDM from M. kansasii were shifted up two or three carbon units higher compared with M. bovis BCG Connaught. Within the rapid grower group, in TDM consisting of a-, keto-and wax ester mycolate from Mycobacterium phlei and Mycobacterium flavescens, the mass ion distribution due to polar mycolates was shifted lower than that from the Mycobacterium avium-intracellulare group. Since the physico-chemical properties and antigenic structure of mycolic acid of TDM affect the host immune responses profoundly, the molecular characterization of TDM by MALDI-TOF mass analysis may give very useful information on the relationship of glycolipid structure to its biological activity.

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“…TDM exists as cell wall bound and secreted forms. TDM bound to the mycobacterial cell wall is non-toxic and protects mycobacteria from killing by the host's macrophages (Hunter et al, 2006;Pan et al, 1999). Secreted TDM accumulates with host lipids in alveoli, a process that rapidly produces caseation necrosis that leads to cavities.…”

mentioning

confidence: 99%

The mycolyltransferase 85A, a putative drug target of Mycobacterium tuberculosis: Development of a novel assay and quantification of glycolipid-status of the mycobacterial cell wall

Elamin

Stehr

Oehlmann

et al. 2009

Journal of Microbiological Methods

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CitationThe mycolyltransferase 85A, a putative drug target of 55 56 57 58 59 60 61 62 63 64 65 66 67 68 The enzymes of the Antigen 85 complex (Ag85A, B, and C) possess mycolyltransferase activity and catalyze the synthesis of the most abundant glycolipid of the mycobacterial cell wall, the cord factor. The cord factor (trehalose 6,6'-dimycolate, TDM) is essential for the integrity of the mycobacterial cell wall and pathogenesis of the bacillus. Thus, TDM biosynthesis is regarded as a potential drug target for control of Mycobacterium tuberculosis infections. Trehalose 6,6'-dimycolate (TDM) is synthesized from two molecules of trehalose-6'-monomycolate (TMM) by antigen 85A. We report here a novel enzyme assay using the natural substrate TMM. The novel colorimetric assay is based on the quantification of glucose from the degradation of trehalose, which is the product from catalytic activity of antigen 85A.Using the new assay, K m and K cat were determined with values of 129.6 ± 8.1 µM and 65.4 ± 4.1 min -1 , respectively. This novel assay is also suitable for robust high-throughput screening (HTS) for compound library screening against mycolyltransferase (antigen 85A). The assay is significantly faster and more convenient to use than all assays currently in use. The assay has a very low coefficient of variance (0.04) in 96-well plates and shows a Z′ factor of 0.67-0.73, indicating the robustness of the assay. In addition, this new assay is highly suitable for the quantification of total TMM of the mycobacterial cell envelope.

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Anti‐Cord Factor (Trehalose 6,6′‐Dimycolate) IgG Antibody in Tuberculosis Patients Recognizes Mycolic Acid Subclasses

Cited by 54 publications

References 27 publications

Immunological Properties of Trehalose Dimycolate (Cord Factor) and Other Mycotic Acid‐Containing Glycolipids–‐A Review

Immunological Properties of Trehalose Dimycolate (Cord Factor) and Other Mycotic Acid‐Containing Glycolipids–‐A Review

Intact molecular characterization of cord factor (trehalose 6,6′-dimycolate) from nine species of mycobacteria by MALDI-TOF mass spectrometry

The mycolyltransferase 85A, a putative drug target of Mycobacterium tuberculosis: Development of a novel assay and quantification of glycolipid-status of the mycobacterial cell wall

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