Conservation and global distribution of non-canonical antigens in Enterotoxigenic Escherichia coli.
Antigens, Bacterial
/ analysis
Enterotoxigenic Escherichia coli
/ chemistry
Escherichia coli Infections
/ immunology
Escherichia coli Proteins
/ analysis
Genetic Variation
Global Health
Humans
Immunoblotting
Membrane Glycoproteins
/ analysis
Peptide Hydrolases
/ analysis
Polymerase Chain Reaction
Whole Genome Sequencing
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
18
07
2019
accepted:
02
10
2019
revised:
06
12
2019
pubmed:
23
11
2019
medline:
12
2
2020
entrez:
23
11
2019
Statut:
epublish
Résumé
Enterotoxigenic Escherichia coli (ETEC) cause significant diarrheal morbidity and mortality in children of resource-limited regions, warranting development of effective vaccine strategies. Genetic diversity of the ETEC pathovar has impeded development of broadly protective vaccines centered on the classical canonical antigens, the colonization factors and heat-labile toxin. Two non-canonical ETEC antigens, the EtpA adhesin, and the EatA mucinase are immunogenic in humans and protective in animal models. To foster rational vaccine design that complements existing strategies, we examined the distribution and molecular conservation of these antigens in a diverse population of ETEC isolates. Geographically diverse ETEC isolates (n = 1159) were interrogated by PCR, immunoblotting, and/or whole genome sequencing (n = 46) to examine antigen conservation. The most divergent proteins were purified and their core functions assessed in vitro. EatA and EtpA or their coding sequences were present in 57.0% and 51.5% of the ETEC isolates overall, respectively; and were globally dispersed without significant regional differences in antigen distribution. These antigens also exhibited >93% amino acid sequence identity with even the most divergent proteins retaining the core adhesin and mucinase activity assigned to the prototype molecules. EtpA and EatA are well-conserved molecules in the ETEC pathovar, suggesting that they serve important roles in virulence and that they could be exploited for rational vaccine design.
Sections du résumé
BACKGROUND
Enterotoxigenic Escherichia coli (ETEC) cause significant diarrheal morbidity and mortality in children of resource-limited regions, warranting development of effective vaccine strategies. Genetic diversity of the ETEC pathovar has impeded development of broadly protective vaccines centered on the classical canonical antigens, the colonization factors and heat-labile toxin. Two non-canonical ETEC antigens, the EtpA adhesin, and the EatA mucinase are immunogenic in humans and protective in animal models. To foster rational vaccine design that complements existing strategies, we examined the distribution and molecular conservation of these antigens in a diverse population of ETEC isolates.
METHODS
Geographically diverse ETEC isolates (n = 1159) were interrogated by PCR, immunoblotting, and/or whole genome sequencing (n = 46) to examine antigen conservation. The most divergent proteins were purified and their core functions assessed in vitro.
RESULTS
EatA and EtpA or their coding sequences were present in 57.0% and 51.5% of the ETEC isolates overall, respectively; and were globally dispersed without significant regional differences in antigen distribution. These antigens also exhibited >93% amino acid sequence identity with even the most divergent proteins retaining the core adhesin and mucinase activity assigned to the prototype molecules.
CONCLUSIONS
EtpA and EatA are well-conserved molecules in the ETEC pathovar, suggesting that they serve important roles in virulence and that they could be exploited for rational vaccine design.
Identifiants
pubmed: 31756188
doi: 10.1371/journal.pntd.0007825
pii: PNTD-D-19-00825
pmc: PMC6897418
doi:
Substances chimiques
Antigens, Bacterial
0
Escherichia coli Proteins
0
EtpA protein, E coli
0
Membrane Glycoproteins
0
EatA protein, E coli
EC 3.4.-
Peptide Hydrolases
EC 3.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0007825Subventions
Organisme : NIAID NIH HHS
ID : R01 AI089894
Pays : United States
Organisme : NIAID NIH HHS
ID : K23 AI130389
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI110820
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI126887
Pays : United States
Organisme : BLRD VA
ID : I01 BX004825
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000448
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI054948
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI095346
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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