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A Novel Protective Vaccine Antigen from the Core Escherichia coli Genome

View Article: PubMed Central - PubMed

ABSTRACT

E. coli is a multifaceted pathogen of major significance to global human health and an important contributor to increasing antibiotic resistance. Given the paucity of therapies still effective against multidrug-resistant pathogenic E. coli strains, novel treatment and prevention strategies are urgently required. In this study, we defined the core and accessory components of the E. coli genome by examining a large collection of draft and completely sequenced strains available from public databases. This data set was mined by employing a reverse-vaccinology approach in combination with proteomics to identify putative broadly protective vaccine antigens. One such antigen was identified that was highly immunogenic and induced protection in a mouse model of bacteremia. Overall, our study provides a genomic and proteomic framework for the selection of novel vaccine antigens that could mediate broad protection against pathogenic E. coli.

No MeSH data available.


The E. coli core genome. The distribution of MG1655 genes among strains in EcoDS is represented by histograms and color coded according to prevalence and subcellular localization (predicted by PSORTb). Only the 4,319 unique genes in the MG1655 genome are shown.
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fig2: The E. coli core genome. The distribution of MG1655 genes among strains in EcoDS is represented by histograms and color coded according to prevalence and subcellular localization (predicted by PSORTb). Only the 4,319 unique genes in the MG1655 genome are shown.

Mentions: We used the 1,556 genome sequences in EcoDS to define the conserved set of E. coli genes. To enable this analysis, we used the well-characterized and best-annotated K-12 strain MG1655 as a reference (23), and based on the essential gene data, a cutoff value for gene prevalence was set at 99%. Pairwise comparison of the 4,319 open reading frames (ORFs) defined in MG1655 with the genome sequence of the 1,556 strains in EcoDS led to the identification of 3,042 genes present in more than 99% of strains (protein identity of >75% over a 75% sequence overlap), of which 1,037 genes were present in 100% of the strains. These 3,042 genes define a conserved subset of E. coli genes in the 1,556 strains that make up EcoDS (Fig. 2; see Data Set S4 in the supplemental material).


A Novel Protective Vaccine Antigen from the Core Escherichia coli Genome
The E. coli core genome. The distribution of MG1655 genes among strains in EcoDS is represented by histograms and color coded according to prevalence and subcellular localization (predicted by PSORTb). Only the 4,319 unique genes in the MG1655 genome are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120174&req=5

fig2: The E. coli core genome. The distribution of MG1655 genes among strains in EcoDS is represented by histograms and color coded according to prevalence and subcellular localization (predicted by PSORTb). Only the 4,319 unique genes in the MG1655 genome are shown.
Mentions: We used the 1,556 genome sequences in EcoDS to define the conserved set of E. coli genes. To enable this analysis, we used the well-characterized and best-annotated K-12 strain MG1655 as a reference (23), and based on the essential gene data, a cutoff value for gene prevalence was set at 99%. Pairwise comparison of the 4,319 open reading frames (ORFs) defined in MG1655 with the genome sequence of the 1,556 strains in EcoDS led to the identification of 3,042 genes present in more than 99% of strains (protein identity of >75% over a 75% sequence overlap), of which 1,037 genes were present in 100% of the strains. These 3,042 genes define a conserved subset of E. coli genes in the 1,556 strains that make up EcoDS (Fig. 2; see Data Set S4 in the supplemental material).

View Article: PubMed Central - PubMed

ABSTRACT

E. coli is a multifaceted pathogen of major significance to global human health and an important contributor to increasing antibiotic resistance. Given the paucity of therapies still effective against multidrug-resistant pathogenic E. coli strains, novel treatment and prevention strategies are urgently required. In this study, we defined the core and accessory components of the E. coli genome by examining a large collection of draft and completely sequenced strains available from public databases. This data set was mined by employing a reverse-vaccinology approach in combination with proteomics to identify putative broadly protective vaccine antigens. One such antigen was identified that was highly immunogenic and induced protection in a mouse model of bacteremia. Overall, our study provides a genomic and proteomic framework for the selection of novel vaccine antigens that could mediate broad protection against pathogenic E. coli.

No MeSH data available.