Major role of iron uptake systems in the intrinsic extra-intestinal virulence of the genus Escherichia revealed by a genome-wide association study

Abstract

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 .

Phylogroup stability contrasts with high within sequence type complex dynamics of Escherichia coli bloodstream infection isolates over a 12-year period

“…7 a). Iron capture systems are the major determinants of intrinsic extra-intestinal virulence [ 69 ]. The emergence of a clone devoid of such systems could be explained by the apparition of other undetected changes, ranging from SNP(s) to gene(s)’ presence/absence linked to increasing fitness.…”

Dynamics of extended-spectrum beta-lactamase-producing Enterobacterales colonization in long-term carriers following travel abroad

“…Carriage durations were compared between strains belonging to the commensalism-associated A/B1/E phylogroups and the extra-intestinal virulence-associated B2/D/F phylogroups using the non-parametric Wilcoxon rank sum test. The rationale of this grouping is based on epidemiological and animal model experimental data [6, 25, 26].…”

Frequency and Diversity of Hybrid Escherichia coli Strains Isolated from Urinary Tract Infections

“…Therefore, additional studies are required to unveil the mechanism involved in the establishment of these infections. Concerning the UPEC/EAEC strains, some studies had pointed out the involvement of aggregative adherence fimbriae (AFF) and other EAEC VFs with the occurrence of extraintestinal infections [ 38 , 39 ] and the importance of yersiniabactin in the development of extraintestinal infections [ 40 ], while is unclear whether any of the aEPEC VFs may play a role in extraintestinal infection.…”