Prediction of new vaccine targets in the core genome of Corynebacterium pseudotuberculosis through omics approaches and reverse vaccinology

Araújo, Carlos; Alves, Jorianne Thyeska Castro; Nogueira, Wylerson Guimarães; Pereira, Lino César; Gomide, Anne Cybelle Pinto; Ramos, Rommel Thiago Jucá; Azevedo, Vasco; Silva, Artur M. S.; Folador, Adriana Ribeiro Carneiro

doi:10.1016/j.gene.2019.03.049

Cited by 31 publications

(25 citation statements)

References 76 publications

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“…This approach is characterized by the classification of genes in three groups: the core genome, which is composed by genes shared by all strains; the accessory genome, which is composed by genes absent in some strains; and the strain-specific genes (Tettelin et al, 2005). Given this, the analysis of genes belonging to the core genome is particularly important, once the presence of orthologues shared by all strains of a biovar can reveal interesting objects of study in the search for new therapeutic or vaccine targets for CLA (Araújo et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

In silico functional prediction of hypothetical proteins from the core genome of Corynebacterium pseudotuberculosis biovar ovis

Araújo

Blanco

Souza

et al. 2020

PeerJ

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Corynebacterium pseudotuberculosis is a pathogen of veterinary relevance diseases, being divided into two biovars: equi and ovis; causing ulcerative lymphangitis and caseous lymphadenitis, respectively. The isolation and sequencing of C. pseudotuberculosis biovar ovis strains in the Northern and Northeastern regions of Brazil exhibited the emergence of this pathogen, which causes economic losses to small ruminant producers, and condemnation of carcasses and skins of animals. Through the pan-genomic approach, it is possible to determine and analyze genes that are shared by all strains of a species—the core genome. However, many of these genes do not have any predicted function, being characterized as hypothetical proteins (HP). In this study, we considered 32 C. pseudotuberculosis biovar ovis genomes for the pan-genomic analysis, where were identified 172 HP present in a core genome composed by 1255 genes. We are able to functionally annotate 80 sequences previously characterized as HP through the identification of structural features as conserved domains and families. Furthermore, we analyzed the physicochemical properties, subcellular localization and molecular function. Additionally, through RNA-seq data, we investigated the differential gene expression of the annotated HP. Genes inserted in pathogenicity islands had their virulence potential evaluated. Also, we have analyzed the existence of functional associations for their products based on protein–protein interaction networks, and perform the structural prediction of three targets. Due to the integration of different strategies, this study can underlie deeper in vitro researches in the characterization of these HP and the search for new solutions for combat this pathogen.

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Section: Introductionmentioning

confidence: 99%

In silico functional prediction of hypothetical proteins from the core genome of Corynebacterium pseudotuberculosis biovar ovis

Araújo

Blanco

Souza

et al. 2020

PeerJ

Self Cite

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“…Only recently such genomic features are being taken into consideration when performing RV, as has been shown for Helicobacter pylori (13), Acinetobacter baumanii (14), Leptospira interrogans (15), pathogenic Brucella spp. (16), and Corynebacterium pseudotuberculosis (17). While these analyses provided the complete decision-tree performed, none of them provided the in-house scripts used for integration of all tools employed in their approaches.…”

Section: Introductionmentioning

confidence: 99%

EpitoCore: Mining Conserved Epitope Vaccine Candidates in the Core Proteome of Multiple Bacteria Strains

2020

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In reverse vaccinology approaches, complete proteomes of bacteria are submitted to multiple computational prediction steps in order to filter proteins that are possible vaccine candidates. Most available tools perform such analysis only in a single strain, or a very limited number of strains. But the vast amount of genomic data had shown that most bacteria contain pangenomes, i.e., their genomic information contains core, conserved genes, and random accessory genes specific to each strain. Therefore, in reverse vaccinology methods it is of the utmost importance to define core proteins and core epitopes. EpitoCore is a decision-tree pipeline developed to fulfill that need. It provides surfaceome prediction of proteins from related strains, defines core proteins within those, calculate their immunogenicity, predicts epitopes for a given set of MHC alleles defined by the user, and then reports if epitopes are located extracellularly and if they are conserved among the core homologs. Pipeline performance is illustrated by mining peptide vaccine candidates in Mycobacterium avium hominissuis strains. From a total proteome of ∼4,800 proteins per strain, EpitoCore predicted 103 highly immunogenic core homologs located at cell surface, many of those related to virulence and drug resistance. Conserved epitopes identified among these homologs allows the users to define sets of peptides with potential to immunize the largest coverage of tested HLA alleles using peptide-based vaccines. Therefore, EpitoCore is able to provide automated identification of conserved epitopes in bacterial pangenomic datasets.

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“…Currently, there are no reliable tests available to diagnose all CL cases. ELISA, using several antigenic preparations, has already been tested (Sutherland et al 1987;Menzies et al 1994;Sting et al 1998;Carminati et al 2003); however, few formulations use recombinant proteins (Menzies et al 1994;Rezende et al 2016; Barral et al 2019;Silva et al 2019). This strategy could signi cantly increase sensitivity and speci city due to the use of a single puri ed antigen (Rezende et al 2016).…”

Section: Introductionmentioning

confidence: 99%

“…The complete sequencing of the C. pseudotuberculosis genome, combined with the introduction of more advanced technologies, such as mass spectrometry, brought new perspectives to the study of proteins excreted by microorganisms as potential therapeutic, vaccine, or immunoassay targets (D'Afonseca et al 2010;Bastos et al 2012;Araújo et al 2019). Some of the highlighted immunoassay and vaccine development target proteins include diptheric toxin repressor homologue (DTxR), Trx and TrxR thioredoxin complex proteins, LexA proteins, superoxide dismutase-C (SodC), SpaC, neuraminidase H (NanH), and PknG serine/threonine kinases (Trost et al 2010;Hall et al 2011;Lin et al 2016;Santana-Jorge et al 2016).…”

Section: Introductionmentioning

confidence: 99%

rSodC is a potential antigen to diagnose Corynebacterium pseudotuberculosis by enzyme-linked immunoassay

Farias¹,

Filho

Marchioro

et al. 2020

Preprint

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Caseous lymphadenitis (CL) is a chronic infectious disease that affects sheep and goats. Many serological tests have been developed to detect the disease; one of the most widely used is the enzyme-linked immunosorbent assay (ELISA), due to its advantages, which include acceptable cost-effectiveness, applicability, sensitivity and specificity. ELISA formulations using recombinant proteins can exhibit significant sensitivity and specificity when using a single purified antigen. DTxR, Trx, TrxR, LexA, SodC, SpaC, NanH, and PknG recombinant proteins can be considered target proteins for ELISA development due to its extracellular or on the cell surface location, which allows a better recognition by the immune system. Therefore, the objectives of this study were to evaluate the antigenic reactivity of Corynebacterium pseudotuberculosis recombinant proteins in goat and sheep serum. Of eight proteins evaluated, rSodC was selected for validation assays with small ruminant serum samples from the semiarid region of the state of Bahia, Brazil. Validation assays with goat serum samples showed that ELISA-rSodC presented sensitivity and specificity of 96% and 94%, respectively. Validation assays with sheep serum showed that ELISA-rSodC exhibited sensitivity and specificity of 95% and 98%, respectively. Analysis of 756 field serum samples showed that rSodC identified 95 positive samples (23%) in goats and 75 positive samples (21%) in sheep. The ELISA with recombinant SodC protein developed in this study discriminated positive and negative serum samples with high levels of sensitivity and specificity. This formulation is promising for epidemiological surveys and CL control programs.

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Prediction of new vaccine targets in the core genome of Corynebacterium pseudotuberculosis through omics approaches and reverse vaccinology

Cited by 31 publications

References 76 publications

In silico functional prediction of hypothetical proteins from the core genome of Corynebacterium pseudotuberculosis biovar ovis

In silico functional prediction of hypothetical proteins from the core genome of Corynebacterium pseudotuberculosis biovar ovis

EpitoCore: Mining Conserved Epitope Vaccine Candidates in the Core Proteome of Multiple Bacteria Strains

rSodC is a potential antigen to diagnose Corynebacterium pseudotuberculosis by enzyme-linked immunoassay

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