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Multi-Omics of Corynebacterium Pseudotuberculosis 12CS0282 and an In Silico Reverse Vaccinology Approach Reveal Novel Vaccine and Drug Targets.

ABSTRACT: Corynebacterium pseudotuberculosis is an important animal pathogen, which is also able to infect humans. An optimal treatment of infections with this pathogen is not available today and consequently, more research is necessary to understand the infection process. Here, we present a combined -omics and bioinformatics approach to characterize C. pseudotuberculosis 12CS0282. The genome sequence of strain 12CS0282 was determined, analyzed in comparison with the available 130 C. pseudotuberculosis sequences and used as a basis for proteome analyses. In a reverse vaccinology approach, putative vaccine and drug targets for 12CS0208 were identified. Mass spectrometry analyses revealed the presence of multiple virulence factors even without host contact. In macrophage interaction studies, C. pseudotuberculosis 12CS0282 was highly resistant against human phagocytes and even multiplied within human THP-1 cells. Taken together, the data indicate a high pathogenic potential of the strain.

SUBMITTER: Moller J

PROVIDER: S-EPMC9784263 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Multi-Omics of Corynebacterium Pseudotuberculosis 12CS0282 and an In Silico Reverse Vaccinology Approach Reveal Novel Vaccine and Drug Targets.

Möller Jens J Bodenschatz Mona M Sangal Vartul V Hofmann Jörg J Burkovski Andreas A

Proteomes 20221123 4

Corynebacterium pseudotuberculosis is an important animal pathogen, which is also able to infect humans. An optimal treatment of infections with this pathogen is not available today and consequently, more research is necessary to understand the infection process. Here, we present a combined -omics and bioinformatics approach to characterize C. pseudotuberculosis 12CS0282. The genome sequence of strain 12CS0282 was determined, analyzed in comparison with the available 130 C. pseu ...[more]

PMID: 36548458

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Project description:BackgroundPan-genomic studies aim, for instance, at defining the core, dispensable and unique genes within a species. A pan-genomics study for vaccine design tries to assess the best candidates for a vaccine against a specific pathogen. In this context, rather than studying genes predicted to be exported in a single genome, with pan-genomics it is possible to study genes present in different strains within the same species, such as virulence factors. The target organism of this pan-genomic work here presented is Corynebacterium pseudotuberculosis, the etiologic agent of caseous lymphadenitis (CLA) in goat and sheep, which causes significant economic losses in those herds around the world. Currently, only a few antigens against CLA are known as being the basis of commercial and still ineffective vaccines. In this regard, the here presented work analyses, in silico, five C. pseudotuberculosis genomes and gathers data to predict common exported proteins in all five genomes. These candidates were also compared to two recent C. pseudotuberculosis in vitro exoproteome results.ResultsThe complete genome of five C. pseudotuberculosis strains (1002, C231, I19, FRC41 and PAT10) were submitted to pan-genomics analysis, yielding 306, 59 and 12 gene sets, respectively, representing the core, dispensable and unique in silico predicted exported pan-genomes. These sets bear 150 genes classified as secreted (SEC) and 227 as potentially surface exposed (PSE). Our findings suggest that the main C. pseudotuberculosis in vitro exoproteome could be greater, appended by a fraction of the 35 proteins formerly predicted as making part of the variant in vitro exoproteome. These genomes were manually curated for correct methionine initiation and redeposited with a total of 1885 homogenized genes.ConclusionsThe in silico prediction of exported proteins has allowed to define a list of putative vaccine candidate genes present in all five complete C. pseudotuberculosis genomes. Moreover, it has also been possible to define the in silico predicted dispensable and unique C. pseudotuberculosis exported proteins. These results provide in silico evidence to further guide experiments in the areas of vaccines, diagnosis and drugs. The work here presented is the first whole C. pseudotuberculosis in silico predicted pan-exoproteome completed till today.

Dataset Information

Multi-Omics of Corynebacterium Pseudotuberculosis 12CS0282 and an In Silico Reverse Vaccinology Approach Reveal Novel Vaccine and Drug Targets.

Publications

Multi-Omics of <i>Corynebacterium Pseudotuberculosis</i> 12CS0282 and an In Silico Reverse Vaccinology Approach Reveal Novel Vaccine and Drug Targets.

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