Major role of iron uptake systems in the intrinsic extra-intestinal virulence of the genus Escherichia revealed by a genome-wide association study.
Animals
Disease Models, Animal
Escherichia coli
/ classification
Escherichia coli Infections
/ genetics
Genetic Variation
/ genetics
Genome-Wide Association Study
Genomic Islands
/ genetics
Humans
Iron
/ metabolism
Mice
Phenols
/ metabolism
Phylogeny
Sepsis
/ genetics
Siderophores
/ genetics
Thiazoles
/ metabolism
Virulence
/ genetics
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
27
04
2020
accepted:
20
08
2020
entrez:
28
10
2020
pubmed:
29
10
2020
medline:
1
1
2021
Statut:
epublish
Résumé
The genus Escherichia is composed of several species and cryptic clades, including E. coli, which behaves as a vertebrate gut commensal, but also as an opportunistic pathogen involved in both diarrheic and extra-intestinal diseases. To characterize the genetic determinants of extra-intestinal virulence within the genus, we carried out an unbiased genome-wide association study (GWAS) on 370 commensal, pathogenic and environmental strains representative of the Escherichia genus phylogenetic diversity and including E. albertii (n = 7), E. fergusonii (n = 5), Escherichia clades (n = 32) and E. coli (n = 326), tested in a mouse model of sepsis. We found that the presence of the high-pathogenicity island (HPI), a ~35 kbp gene island encoding the yersiniabactin siderophore, is highly associated with death in mice, surpassing other associated genetic factors also related to iron uptake, such as the aerobactin and the sitABCD operons. We confirmed the association in vivo by deleting key genes of the HPI in E. coli strains in two phylogenetic backgrounds. We then searched for correlations between virulence, iron capture systems and in vitro growth in a subset of E. coli strains (N = 186) previously phenotyped across growth conditions, including antibiotics and other chemical and physical stressors. We found that virulence and iron capture systems are positively correlated with growth in the presence of numerous antibiotics, probably due to co-selection of virulence and resistance. We also found negative correlations between virulence, iron uptake systems and growth in the presence of specific antibiotics (i.e. cefsulodin and tobramycin), which hints at potential "collateral sensitivities" associated with intrinsic virulence. This study points to the major role of iron capture systems in the extra-intestinal virulence of the genus Escherichia.
Identifiants
pubmed: 33112851
doi: 10.1371/journal.pgen.1009065
pii: PGENETICS-D-20-00657
pmc: PMC7592755
doi:
Substances chimiques
Phenols
0
Siderophores
0
Thiazoles
0
yersiniabactin
0
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009065Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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