The Structure of Mycobacterium tuberculosis MPT51 (FbpC1) Defines a New Family of Non-catalytic α/β Hydrolases

Wilson, Rosalind A.; Maughan, William N.; Kremer, Laurent; Besra, Gurdyal S.; Fütterer, Klaus

doi:10.1016/j.jmb.2003.11.001

Cited by 45 publications

(39 citation statements)

References 55 publications

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“…The 27-kDa protein MPT51, a culture filtrate protein, is closely related to the antigen 85 (Ag85) complex, which comprises Ag85A, Ag85B, and Ag85C. MPT51 is an adhesin (108) reported to be a fibronectin-binding protein of M. tuberculosis (113). A sufficient number of studies evaluating the performance of MPT51 were available to stratify the results by HIV infection status.…”

Section: Resultsmentioning

confidence: 99%

Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a Meta-Analysis

Steingart

Dendukuri

Henry

et al. 2009

Clin Vaccine Immunol

170

137

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The failure to diagnose tuberculosis (TB) accurately and rapidly is a key challenge in curbing the epidemic (45,88,116). Sputum microscopy, currently the sole diagnostic test in most areas where TB is endemic, has several limitations; in particular, the sensitivity compared with that of culture is variable (80,97,104,116), multiple patient visits are required (56,93,114), considerable technical training is necessary, and the procedure is labor-intensive (45, 65). Antibody detection tests (serological tests) are used for the diagnosis of many infectious diseases and could potentially improve the means of diagnosis of TB. These tests measure the presence of specific antibodies (most often immunoglobulin G [IgG]) directed against immunodominant antigens of the pathogen in question. Compared with microscopy, antibody detection methods may enable the rapid diagnosis of TB, as these tests have the advantages of speed (results can be available within hours), technological simplicity, and minimal training requirements. In addition, these tests can be adapted to point-of-care formats that can be implemented at lower levels of health services in low-and middle-income countries (21,22,57,65).Efforts to develop antibody detection tests for the diagnosis of TB have been under way for decades, and the performance of these tests has been well described (13,17,22,32,40,47,48,52,60,64,100,107). Several systematic reviews of these tests have been published (discussed below) (28,94,95).First-generation antibody detection tests were based on crude mixtures of constituents and products of Mycobacterium tuberculosis, for example, culture filtrate proteins and purified protein derivative, the preparation used in the tuberculin skin test. Several of these early tests had low specificities, as the tests contained antigens shared among different bacterial species (1,22,48,57). During the past two decades, an increased understanding of humoral immune responses to M. tuberculosis and the new tools of

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Section: Resultsmentioning

confidence: 99%

Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a Meta-Analysis

Steingart

Dendukuri

Henry

et al. 2009

Clin Vaccine Immunol

170

137

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“…However, these FbpD paralogs do not contain the carboxyesterase domain needed for mycolyltransferase activity (Fig. 2D); furthermore, structural determination showed that FbpD MTB lacked catalytic elements required for mycolyltransferase activity as well as ␣,␣Ј-trehalose monomycolate-binding sites (39,40). Mycolyltransferase activity of FbpD MTB was not detected in vitro (19).…”

Section: Discussionmentioning

confidence: 99%

“…Mycolyltransferase activity of FbpD MTB was not detected in vitro (19). Nevertheless, retention of the gene, especially in the downsized M. leprae genome, suggests its utility, perhaps providing an altered catalytic activity or a nonenzymatic function (39,40). To examine whether a polar effect of the transposon on fbpD MS expression was involved in MAR1 phenotypes, the gene was placed under the control of the hsp60 promoter.…”

Section: Discussionmentioning

confidence: 99%

FbpA-Dependent Biosynthesis of Trehalose Dimycolate Is Required for the Intrinsic Multidrug Resistance, Cell Wall Structure, and Colonial Morphology of Mycobacterium smegmatis

2005

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Ligation of mycolic acids to structural components of the mycobacterial cell wall generates a hydrophobic, impermeable barrier that provides resistance to toxic compounds such as antibiotics. Secreted proteins FbpA, FbpB, and FbpC attach mycolic acids to arabinogalactan, generating mycolic acid methyl esters (MAME) or trehalose, generating ␣,␣-trehalose dimycolate (TDM; also called cord factor). Our studies of Mycobacterium smegmatis showed that disruption of fbpA did not affect MAME levels but resulted in a 45% reduction of TDM. The fbpA mutant displayed increased sensitivity to both front-line tuberculosis-targeted drugs as well as other broad-spectrum antibiotics widely used for antibacterial chemotherapy. The irregular, hydrophobic surface of wild-type M. smegmatis colonies became hydrophilic and smooth in the mutant. While expression of M. smegmatis fbpA restored defects of the mutant, heterologous expression of the Mycobacterium tuberculosis fbpA gene was less effective. A single mutation in the M. smegmatis FbpA esterase domain inactivated its ability to provide antibiotic resistance. These data show that production of TDM by FbpA is essential for the intrinsic antibiotic resistance and normal colonial morphology of some mycobacteria and support the concept that FbpA-specific inhibitors, alone or in combination with other antibiotics, could provide an effective treatment to tuberculosis and other mycobacterial diseases.

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“…Several conserved residues of these proteins represent potential sites for interaction with human fibronectin (32;33), and they are also known as fibronectin-binding proteins (Fbp) A, B and C. The degree of sequence homology between MPT 51 and the members of the Ag 85 complex and the previous demonstration that it can bind fibronectin (34), led to speculations that this protein might constitute a forth member of this complex. However, MPT51 does not have structural elements that are required for mycolyltrandferase activity (16), suggesting that it may have function/s that is/are different than that/those of the members of Antigen 85 complex.…”

Section: Discussionmentioning

confidence: 99%

“…tuberculosis CDC 1551 whole cell lysate, cytosol, cell wall, membrane and culture filtrate protein as well as M. tuberculosis H37Rv LAM, mycolyl arabinogalactan-peptidoglycan complex (mAGP), total lipid fractions, and mycolic acids were supplied by J. T. Belisle. MPT51 was generated as previously described (16).…”

Section: Antigensmentioning

confidence: 99%

Monoclonal antibodies to Mycobacterium tuberculosis CDC 1551 reveal subcellular localization of MPT51

Al-Sayyed¹,

Piperdi²,

Yuan³

et al. 2007

Tuberculosis

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Mycobacterium tuberculosis CDC 1551, a highly immunogenic outbreak strain, previously reported to have unique surface distribution of capsular polysaccharide, was used to generate novel monoclonal antibodies (mAbs) to surface mycobacterial targets. Two Immunoglobulin G1 (IgG1) mAbs, 16a1 and 16a6 were generated. The mAbs originated from the same B cell, bound strongly to whole cell M. tuberculosis CDC1551 and to its cell wall, membrane and cytosol fractions recognizing a 90 kDa protein. Immunoprecipitation using mAb 16a1 isolated a protein with amino acid peptide sequences matching MPT51 from the cytosol. This immunogenic protein of unknown function, was previously reported only in culture filtrates of M. tuberculosis. Our findings suggest for the first time that this protein is found within the M. tuberculosis cell.

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The Structure of Mycobacterium tuberculosis MPT51 (FbpC1) Defines a New Family of Non-catalytic α/β Hydrolases

Cited by 45 publications

References 55 publications

Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a Meta-Analysis

Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a Meta-Analysis

FbpA-Dependent Biosynthesis of Trehalose Dimycolate Is Required for the Intrinsic Multidrug Resistance, Cell Wall Structure, and Colonial Morphology of Mycobacterium smegmatis

Monoclonal antibodies to Mycobacterium tuberculosis CDC 1551 reveal subcellular localization of MPT51

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