A microbiological and genomic perspective of globally collected Escherichia coli from adults hospitalized with invasive E. coli disease

Abstract

Objectives: Escherichia coli can cause infections in the urinary tract and in normally sterile body sites leading to invasive E. coli disease (IED), including bacteraemia and sepsis, with older populations at increased risk. We aimed to estimate the theoretical coverage rate by the ExPEC4V and 9V vaccine candidates. In addition, we aimed at better understanding the diversity of E. coli isolates, including their genetic and phenotypic antimicrobial resistance (AMR), sequence types (STs), O-serotypes and the bacterial population structure.

Methods: Blood and urine culture E. coli isolates (n = 304) were collected from hospitalized patients ≥60 years (n = 238) with IED during a multicentric, observational study across three continents. All isolates were tested for antimicrobial susceptibility, O-serotyped, whole-genome sequenced and bioinformatically analysed.

Results: A large diversity of STs and of O-serotypes were identified across all centres, with O25b-ST131, O6-ST73 and O1-ST95 being the most prevalent types. A total of 45.4% and 64.7% of all isolates were found to have an O-serotype covered by the ExPEC4V and ExPEC9V vaccine candidates, respectively. The overall frequency of MDR was 37.4% and ST131 was predominant among MDR isolates. Low in-patient genetic variability was observed in cases where multiple isolates were collected from the same patient.

Conclusions: Our results highlight the predominance of MDR O25b-ST131 E. coli isolates across diverse geographic areas. These findings provide further baseline data on the theoretical coverage of novel vaccines targeting E. coli associated with IED in older adults and their associated AMR levels.

Figure 1.

Overview of isolate collections used for analyses. The full data collection contains 304 E. coli isolates. The unique isolate collection contains 238 isolates whereas the paired isolate collection comprises 128 isolates.

Figure 2.

Distribution of ST (present in ≥5 isolates) and O-serotypes (present in ≥7 isolates). STs and O-serotypes present in, respectively, five or fewer and seven or fewer isolates are summarized as ‘other’. (a) The proportion of STs across hospital sites. (b) The pairwise correlation of STs with Clermont phylogroups. The magnitude of the circles indicates the number of isolates following the legend. (c) The proportion of O-serotypes across hospital sites. D The pairwise correlation of O-serotypes and ST. The magnitude of the circles indicates the number of isolates following the legend.

Figure 3.

The population structure of extra-intestinal pathogenic E. coli is represented by a midpoint-rooted maximum-likelihood phylogenetic tree of the unique isolate collection (238 isolates), based on 1000 bootstraps. Core genomes of the isolates in this study and the reference genome E. coli K-12 were aligned. The tree is based on 139 932 SNPs. Coloured ranges represent predominant STs found in more than five isolates. Rings 1, 2 and 3 denote the hospital site, vaccine coverage by ExPEC4V and ExPEC9V, and multidrug resistance (MDR). Rings 4, 5 and 6 show resistance to cephalosporins, fluoroquinolones and aminoglycosides. The scale bar indicates the number of SNPs per site in the core genome alignment. The tree was visualized using iTOL.

Figure 4.

Number and ratio of isolates theoretically covered by the ExPEC4V and ExPEC9V vaccine candidate. The bar chart is coloured by the prevalence of O-serotypes in this study collection (unique isolate collection). The coverage in the ExPEC4V and ExPEC9V vaccines is coloured in shades of grey.