Identification of Secreted Proteins of<i>Mycobacterium tuberculosis</i>by a Bioinformatic Approach

Gomez, Manuel; Johnson, Sadie; Gennaro, Maria Laura

doi:10.1128/iai.68.4.2323-2327.2000

Cited by 97 publications

(66 citation statements)

References 38 publications

(18 reference statements)

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“…The latter view is supported by the identification of typical cytoplasmic proteins, such as aldolases, enolases, elongation factor G, GroEL, superoxide dismutase, and various dehydrogenases, which were also detected in the extracellular proteome of B. subtilis (5). Strikingly, of the 31 proteins that were found exclusively in the medium fraction, only 5 are synthesized with a putative N-terminal signal peptide as previously predicted (43). However, it should be noted that proteins that contain transmembrane domains in addition to a signal peptide were excluded from the latter predictions.…”

Section: Mycobacterium Tuberculosissupporting

confidence: 52%

Proteomics of Protein Secretion by Bacillus subtilis : Separating the “Secrets” of the Secretome

Tjalsma¹,

Antelmann

Jongbloed³

et al. 2004

Microbiol Mol Biol Rev

514

519

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SUMMARY Secretory proteins perform a variety of important“ remote-control” functions for bacterial survival in the environment. The availability of complete genome sequences has allowed us to make predictions about the composition of bacterial machinery for protein secretion as well as the extracellular complement of bacterial proteomes. Recently, the power of proteomics was successfully employed to evaluate genome-based models of these so-called secretomes. Progress in this field is well illustrated by the proteomic analysis of protein secretion by the gram-positive bacterium Bacillus subtilis, for which ∼90 extracellular proteins were identified. Analysis of these proteins disclosed various“ secrets of the secretome,” such as the residence of cytoplasmic and predicted cell envelope proteins in the extracellular proteome. This showed that genome-based predictions reflect only∼ 50% of the actual composition of the extracellular proteome of B. subtilis. Importantly, proteomics allowed the first verification of the impact of individual secretion machinery components on the total flow of proteins from the cytoplasm to the extracellular environment. In conclusion, proteomics has yielded a variety of novel leads for the analysis of protein traffic in B. subtilis and other gram-positive bacteria. Ultimately, such leads will serve to increase our understanding of virulence factor biogenesis in gram-positive pathogens, which is likely to be of high medical relevance.

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Section: Mycobacterium Tuberculosissupporting

confidence: 52%

Proteomics of Protein Secretion by Bacillus subtilis : Separating the “Secrets” of the Secretome

Tjalsma¹,

Antelmann

Jongbloed³

et al. 2004

Microbiol Mol Biol Rev

514

519

View full text Add to dashboard Cite

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“…First, 148 open reading frames were selected from groups which were either secreted proteins, or from regions of the M. bovis genome known to be deleted in M. bovis BCG. Secreted proteins are known to be important among mycobacterial antigens (2), and therefore a total of 96 proteins were included in this group because they have been identified as secreted either by proteomic studies (21,36) or by computer analysis with the SignalP and SPScan programs (15). The second group of proteins consisted of proteins known to be deleted in M. bovis BCG strains (4,16,24).…”

Section: Resultsmentioning

confidence: 99%

Genomic Approach to Identification of Mycobacterium bovis Diagnostic Antigens in Cattle

et al. 2003

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Differential delayed-type hypersensitivity skin testing with tuberculin purified protein derivatives from Mycobacterium bovis and M. avium is the standard for diagnosing bovine tuberculosis. However, improved tests based on defined, specific antigens are urgently needed. In the present study, a combination of bioinformatics, molecular biology, and bovine models of infection were used to screen mycobacterial proteins for their potential as diagnostic reagents which could be used in a whole-blood assay for diagnosis of tuberculosis. Initial screening of 28 proteins selected in silico and expressed as recombinants in Escherichia coli indicated that CFP-10, ESAT-6, TB27.4, TB16.2, TB15.8, and TB10.4 induced strong gamma interferon responses in experimentally infected cattle. A more thorough investigation over time in two groups of animals infected with a high (10 6 CFU) and a low (10 4 CFU) dose of M. bovis revealed that, for both groups, the strength of the in vitro response to individual antigens varied greatly over time. However, combining the results for ESAT-6, CFP-10, and TB27.4, possibly supplemented with TB10.4, gave sensitivities at different infection stages close to those obtained with M. bovis purified protein derivative. Importantly, while responsiveness to ESAT-6 and CFP-10 correlated strongly for individual samples, the same was not the case for ESAT-6 and TB27.4 responsiveness. The results suggest that combinations of specific antigens such as these have great potential in development of optimized diagnostic systems for bovine tuberculosis.

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“…Other authors analysed the 3,924 protein-encoding sequences deduced from the M. tuberculosis genome, and identified 52 proteins carrying an aminoterminal secretory signal peptide, but lacking additional membraneanchoring moieties. Of these 52 proteins, only 7 had been previously reported to be secreted proteins [232]. Secreted proteins are good candidates as protective antigens.…”

Section: Exploitation Of the Genome Sequencementioning

confidence: 99%

M. tuberculosis: immunology and vaccination

2001

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Tuberculosis is increasing. Current treatment regimens require at least 6 months, because latent or stationary phase organisms are difficult to kill. Such regimens do not achieve full compliance, and "directly observed therapy short course" (DOTS) is having less impact than expected. This worrying situation is aggravated by coinfection with human immunodeficiency virus (HIV), and by the increase in drug-resistant strains.We need new insights that lead to more rapid therapies and immunotherapies, and more reliable vaccines.Recent insights have come from: understanding of the relationship between Mycobacterium tuberculosis and macrophages; the multiple T cell types that recognise mycobacterial peptides, lipids and glycolipids; the critical role of interferon-c (IFNc) and interleukin-12 (IL-12) in human mycobacterial infection revealed by genetically defective children; quantitation of the presence and importance of Th2 lymphocyte activation in human tuberculosis; the role of local conversion of inactive cortisone to active cortisol in the lesions; the recognition that some effective prophylactic vaccines also work as immumotherapeutics whereas others do not. In the longer term the recent sequencing of the M. tuberculosis genome will lead to further advances.In the short term, effective immunotherapy remains the most accessible breakthrough in the management of tuberculosis. The types of practical advance that will result from sequencing the genome are discussed speculatively, but cannot yet be predicted with certainty.

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Identification of Secreted Proteins ofMycobacterium tuberculosisby a Bioinformatic Approach

Cited by 97 publications

References 38 publications

Proteomics of Protein Secretion by Bacillus subtilis : Separating the “Secrets” of the Secretome

Proteomics of Protein Secretion by Bacillus subtilis : Separating the “Secrets” of the Secretome

Genomic Approach to Identification of Mycobacterium bovis Diagnostic Antigens in Cattle

M. tuberculosis: immunology and vaccination

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