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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.


Related in: MedlinePlus

Phylogeny of E. coli strains in EcoDS. Phylogenetic tree demonstrating the relationship of MLSTs in EcoDS. Major phylogroups A, B1, B2, and D, as well as minor phylogroups E, F, C-I, and C-III to -V, are indicated. Completely sequenced strains are indicated according to their pathotype association (see the inset for the color-coded legend): (i) O157 strains, EDL933, Sakai, TW14359, EC4115, and Xuzhou21; (ii) K-12 strains, MC4100, MDS42, W3110, MG1655, c321.deltaA, and BW2952; and (iii) B strains, REL606, BL21(DE3), and BL21-Gold(DE3)(pLysS) AG. Histograms represent the number of genomes in the respective ST within EcoDS. STs represented by more than 50 genomes are indicated. Open circles represent STs that belong to a different phylogroup.
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fig1: Phylogeny of E. coli strains in EcoDS. Phylogenetic tree demonstrating the relationship of MLSTs in EcoDS. Major phylogroups A, B1, B2, and D, as well as minor phylogroups E, F, C-I, and C-III to -V, are indicated. Completely sequenced strains are indicated according to their pathotype association (see the inset for the color-coded legend): (i) O157 strains, EDL933, Sakai, TW14359, EC4115, and Xuzhou21; (ii) K-12 strains, MC4100, MDS42, W3110, MG1655, c321.deltaA, and BW2952; and (iii) B strains, REL606, BL21(DE3), and BL21-Gold(DE3)(pLysS) AG. Histograms represent the number of genomes in the respective ST within EcoDS. STs represented by more than 50 genomes are indicated. Open circles represent STs that belong to a different phylogroup.

Mentions: Phylogenetic group determination and multilocus sequence typing (MLST) were performed to characterize the relationship of all of the strains in EcoDS. Using this combined analysis, a phylogenetic tree was constructed based on 435 unique MLSTs identified in EcoDS (Fig. 1). This strategy confirmed the strong correlation between E. coli STs and the established multilocus enzyme electrophoresis (MLEE)-based E. coli phylogeny (11) and described a comprehensive distribution of STs within the major phylogroups in EcoDS (Fig. 1).


A Novel Protective Vaccine Antigen from the Core Escherichia coli Genome
Phylogeny of E. coli strains in EcoDS. Phylogenetic tree demonstrating the relationship of MLSTs in EcoDS. Major phylogroups A, B1, B2, and D, as well as minor phylogroups E, F, C-I, and C-III to -V, are indicated. Completely sequenced strains are indicated according to their pathotype association (see the inset for the color-coded legend): (i) O157 strains, EDL933, Sakai, TW14359, EC4115, and Xuzhou21; (ii) K-12 strains, MC4100, MDS42, W3110, MG1655, c321.deltaA, and BW2952; and (iii) B strains, REL606, BL21(DE3), and BL21-Gold(DE3)(pLysS) AG. Histograms represent the number of genomes in the respective ST within EcoDS. STs represented by more than 50 genomes are indicated. Open circles represent STs that belong to a different phylogroup.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Phylogeny of E. coli strains in EcoDS. Phylogenetic tree demonstrating the relationship of MLSTs in EcoDS. Major phylogroups A, B1, B2, and D, as well as minor phylogroups E, F, C-I, and C-III to -V, are indicated. Completely sequenced strains are indicated according to their pathotype association (see the inset for the color-coded legend): (i) O157 strains, EDL933, Sakai, TW14359, EC4115, and Xuzhou21; (ii) K-12 strains, MC4100, MDS42, W3110, MG1655, c321.deltaA, and BW2952; and (iii) B strains, REL606, BL21(DE3), and BL21-Gold(DE3)(pLysS) AG. Histograms represent the number of genomes in the respective ST within EcoDS. STs represented by more than 50 genomes are indicated. Open circles represent STs that belong to a different phylogroup.
Mentions: Phylogenetic group determination and multilocus sequence typing (MLST) were performed to characterize the relationship of all of the strains in EcoDS. Using this combined analysis, a phylogenetic tree was constructed based on 435 unique MLSTs identified in EcoDS (Fig. 1). This strategy confirmed the strong correlation between E. coli STs and the established multilocus enzyme electrophoresis (MLEE)-based E. coli phylogeny (11) and described a comprehensive distribution of STs within the major phylogroups in EcoDS (Fig. 1).

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.


Related in: MedlinePlus