A Database for Mycobacterium Secretome Analysis: ‘MycoSec’ to Accelerate Global Health Research

Roy, Ayan; Bhattacharya, Sanghati; Bothra, Asim K.; Sen, Arnab

doi:10.1089/omi.2013.0015

Cited by 10 publications

(9 citation statements)

References 49 publications

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“…Our results showed that our bioinformatics pipeline is quite accurate to predict a complete set of the secreted/excreted proteins in M. tuberculosis genomes. In this regard, our data indicates that ~70% of the experimental secretome was also predicted as secreted using our bioinformatics approach, while only the 34.32 and 41.42 % of the experimental secretome was found in the secretomes reported by Roy et al ( 2013 ) and Vizcaíno et al ( 2010 ), respectively. Furthermore, the maximum coincidence of the experimental secretome against 1000 randomly constructed secretomes was of 45.3%, indicating that our predicted secretomes are also significantly different to the random.…”

Section: Discussionmentioning

confidence: 59%

“…Additionally, we also matched the experimental secretome that we compiled from the literature search with the ones previously reported by Roy et al ( 2013 ) and Vizcaíno et al ( 2010 ). However, we found that only the 34.32 and 41.42% of the experimental secretome was shared with the secretome reported by Roy et al ( 2013 ) and Vizcaíno et al ( 2010 ), respectively (Figure S2 ). These results suggest that the bioinformatics pipeline we used is better to predict a complete set of excreted/secreted proteins in M. tuberculosis genomes.…”

Section: Resultsmentioning

confidence: 99%

“…For example, the secretome reported by Vizcaíno et al ( 2010 ) also used the same 4 predictors that we used; however, they do not eliminate the transmembrane proteins in their secretome. While the secretome reported by Roy et al ( 2013 ), only utilized the secreted proteins by SignalP followed by TATFIND1.4, PRED-LIPO, and the application of TMHMM analysis but only in a selected subgroup of proteins. Our bioinformatics pipeline could be useful to predict secretomes in other pathogen bacteria genomes.…”

Section: Discussionmentioning

confidence: 99%

“…However, only one protein from each predictor was selected and experimentally confirmed as secreted (Vizcaíno et al, 2010 ). In a second study, the authors reported a database composed of 276 secreted proteins for the H37Rv genome using different bioinformatics algorithms (Roy et al, 2013 ) and they found that 46 from 57 experimentally confirmed secreted proteins were predicted in their secretome (Roy et al, 2013 ). However, neither of the two studies provided annotation analysis, biochemical pathway mapping, protein domain content or antigenic potential of their M. tuberculosis predicted secretomes.…”

Section: Introductionmentioning

confidence: 99%

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Secretome Prediction of Two M. tuberculosis Clinical Isolates Reveals Their High Antigenic Density and Potential Drug Targets

et al. 2017

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The Excreted/Secreted (ES) proteins play important roles during Mycobacterium tuberculosis invasion, virulence, and survival inside the host and they are a major source of immunogenic proteins. However, the molecular complexity of the bacillus cell wall has made difficult the experimental isolation of the total bacterial ES proteins. Here, we reported the genomes of two Beijing genotype M. tuberculosis clinical isolates obtained from patients from Vietnam (isolate 46) and South Africa (isolate 48). We developed a bioinformatics pipeline to predict their secretomes and observed that ~12% of the genome-encoded proteins are ES, being PE, PE-PGRS, and PPE the most abundant protein domains. Additionally, the Gene Ontology, KEGG pathways and Enzyme Classes annotations supported the expected functions for the secretomes. The ~70% of an experimental secretome compiled from literature was contained in our predicted secretomes, while only the 34–41% of the experimental secretome was contained in the two previously reported secretomes for H37Rv. These results suggest that our bioinformatics pipeline is better to predict a more complete set of ES proteins in M. tuberculosis genomes. The predicted ES proteins showed a significant higher antigenic density measured by Abundance of Antigenic Regions (AAR) value than the non-ES proteins and also compared to random constructed secretomes. Additionally, we predicted the secretomes for H37Rv, H37Ra, and two M. bovis BCG genomes. The antigenic density for BGG and for isolates 46 and 48 was higher than the observed for H37Rv and H37Ra secretomes. In addition, two sets of immunogenic proteins previously reported in patients with tuberculosis also showed a high antigenic density. Interestingly, mice infected with isolate 46 showed a significant lower survival rate than the ones infected with isolate 48 and both survival rates were lower than the one previously reported for the H37Rv in the same murine model. Finally, after a druggability analysis of the secretomes, we found potential drug targets such as cytochrome P450, thiol peroxidase, the Ag85C, and Ribonucleoside Reductase in the secreted proteins that could be used as drug targets for novel treatments against Tuberculosis.

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Section: Discussionmentioning

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Secretome Prediction of Two M. tuberculosis Clinical Isolates Reveals Their High Antigenic Density and Potential Drug Targets

et al. 2017

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“…The results obtained from these independent studies reveal a remarkable consistency of the Mtb culture filtrate proteome composed of a thousand proteins. It is noteworthy that only a limited number (95/1007; <10%;) of the proteins identified are actually predicted to be secreted and hence susceptible to correspond to secreted mannoproteins [38].…”

Section: Mtb Culture Filtrate Proteome Coverage Using Sds-page Separamentioning

confidence: 99%

Potential Plasticity of the Mannoprotein Repertoire Associated to Mycobacterium tuberculosis Virulence Unveiled by Mass Spectrometry-Based Glycoproteomics

et al. 2020

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To date, Mycobacterium tuberculosis (Mtb) remains the world’s greatest infectious killer. The rise of multidrug-resistant strains stresses the need to identify new therapeutic targets to fight the epidemic. We previously demonstrated that bacterial protein-O-mannosylation is crucial for Mtb infectiousness, renewing the interest of the bacterial-secreted mannoproteins as potential drug-targetable virulence factors. The difficulty of inventorying the mannoprotein repertoire expressed by Mtb led us to design a stringent multi-step workflow for the reliable identification of glycosylated peptides by large-scale mass spectrometry-based proteomics. Applied to the differential analyses of glycoproteins secreted by the wild-type Mtb strain—and by its derived mutant invalidated for the protein-O-mannosylating enzyme PMTub—this approach led to the identification of not only most already known mannoproteins, but also of yet-unknown mannosylated proteins. In addition, analysis of the glycoproteome expressed by the isogenic recombinant Mtb strain overexpressing the PMTub gene revealed an unexpected mannosylation of proteins, with predicted or demonstrated functions in Mtb growth and interaction with the host cell. Since in parallel, a transient increased expression of the PMTub gene has been observed in the wild-type bacilli when infecting macrophages, our results strongly suggest that the Mtb mannoproteome may undergo adaptive regulation during infection of the host cells. Overall, our results provide deeper insights into the complexity of the repertoire of mannosylated proteins expressed by Mtb, and open the way to novel opportunities to search for still-unexploited potential therapeutic targets.

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Biosynthetic energy cost of potentially highly expressed proteins vary with niche in selected actinobacteria

et al. 2017

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Amino acid and protein biosynthesis requires a number of high energy phosphate bonds and includes a dual energy cost for the synthesis of chemical intermediates during the fueling reactions and the conversion of precursor molecules to final products. One popular hypothesis is that the proteins encoded by putative highly expressed genes (hence called PHXPs) generally utilize low energy consuming amino acids to reduce the biosynthetic cost of the essential proteins. In our study, we found that this idea was not supported in the case of actinobacteria. With the actinobacteria, the energy costs of PHXPs varied in relation to their niche. Free-living, including aquatic, soil and extremophilic, and plant-associated actinobacteria were found to use energetically expensive amino acids in their PHXPs. An exception occurred with some animal-host-associated actinobacteria that used energy efficient amino acids. One explanation for these results may be due to the diverse metabolic patterns exhibited by actinobacteria under varied niches influenced by nutritional availability and physical environment.

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A Database for Mycobacterium Secretome Analysis: ‘MycoSec’ to Accelerate Global Health Research

Cited by 10 publications

References 49 publications

Secretome Prediction of Two M. tuberculosis Clinical Isolates Reveals Their High Antigenic Density and Potential Drug Targets

Secretome Prediction of Two M. tuberculosis Clinical Isolates Reveals Their High Antigenic Density and Potential Drug Targets

Potential Plasticity of the Mannoprotein Repertoire Associated to Mycobacterium tuberculosis Virulence Unveiled by Mass Spectrometry-Based Glycoproteomics

Biosynthetic energy cost of potentially highly expressed proteins vary with niche in selected actinobacteria

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