Abstract
Yersinia pseudotuberculosis is one of the three pathogenic species of the genus Yersinia. Most studies regarding pathogenesis of Y. pseudotuberculosis are based on the proteins related to Type III secretion system, which is a well-known primary virulence factor in pathogenic Gram-negative bacteria, including Y. pseudotuberculosis. Information related to the factors involved in Y. pseudotuberculosis granuloma formation is scarce. In the present study we have used a computational approach to identify proteins that might be potentially involved in formation of Y. pseudotuberculosis granuloma. A comparative proteome analysis and conserved orthologous protein identification was performed between two different genera of bacteria - Mycobacterium and Yersinia, their only common pathogenic trait being ability to form necrotizing granuloma. Comprehensive analysis of orthologous proteins was performed in proteomes of seven bacterial species. This included M. tuberculosis, M. bovis and M. avium paratuberculosis - the known granuloma forming Mycobacterium species, Y. pestis and Y. frederiksenii - the non-granuloma forming Yersinia species and, Y. enterocolitica - that forms micro-granuloma and, Y. pseudotuberculosis - a prominent granuloma forming Yersinia species. In silico proteome analysis indicated that seven proteins (UniProt id A0A0U1QT64, A0A0U1QTE0, A0A0U1QWK3, A0A0U1R1R0, A0A0U1R1Z2, A0A0U1R2S7, A7FMD4) might play some role in Y. pseudotuberculosis granuloma. Validation of the probable involvement of the seven proposed Y. pseudotuberculosis granuloma proteins was done using transcriptome data analysis and, by mapping on a composite protein-protein interaction map of experimentally proved M. tuberculosis granuloma proteins (RD1 locus proteins, ESAT-6 secretion system proteins and intra-macrophage secreted proteins). Though, additional experiments involving knocking out of each of these seven proteins are required to confirm their role in Y. pseudotuberculosis granuloma our study can serve as a basis for further studies on Y. pseudotuberculosis granuloma.
Highlights
Yersinia pseudotuberculosis is one of the three pathogenic species of the genus Yersinia
The rationale of our study was based on following basic premises: (a) proteins, which are present in all the seven proteomes, should be the part of conserved core gene set and should be involved in house-keeping functions, (b) proteins which are present in all the species of either Yersinia or mycobacteria should be involved in genus-specific house-keeping functions and, (c) if we remove the proteins of category (a) and (b) the only common proteins between Y. pseudotuberculosis (Yps) and Mycobacterium spp. might be the proteins which help in granuloma formation, as these proteins are not shared with other species of Yersinia
A comparative in-silico analysis of the conserved orthologs of Y. enterocolitica (Yen), Y. pestis (Ype), Yps, Y. frederiksenii (Yfr), M. avium paratuberculosis (Map), M. bovis (Mbov) and M. tuberculosis (Mtb) proteomes was performed to predict proteins that might be involved in Yps granuloma formation
Summary
Yersinia pseudotuberculosis is one of the three pathogenic species of the genus Yersinia. Comprehensive analysis of orthologous proteins was performed in proteomes of seven bacterial species This included M. tuberculosis, M. bovis and M. avium paratuberculosis - the known granuloma forming Mycobacterium species, Y. pestis and Y. frederiksenii - the non-granuloma forming Yersinia species and, Y. enterocolitica - that forms micro-granuloma and, Y. pseudotuberculosis - a prominent granuloma forming Yersinia species. The rationale of our study was based on following basic premises: (a) proteins, which are present in all the seven proteomes, should be the part of conserved core gene set and should be involved in house-keeping functions, (b) proteins which are present in all the species of either Yersinia or mycobacteria should be involved in genus-specific house-keeping functions and, (c) if we remove the proteins of category (a) and (b) the only common proteins between Yps and Mycobacterium spp. might be the proteins which help in granuloma formation, as these proteins are not shared with other species of Yersinia. Functional annotation of these proteins suggested involvement of these proteins in granuloma formation in Yps
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