Urinary tract infections are extremely common and often caused by Escherichia coli. Bacterial virulence factors and patient characteristics have been linked separately to progressive, invasive infection. The interaction of these factors has however rarely been considered. We whole genome sequenced 1076 E. coli isolates recovered from urine- or blood culture samples from 825 clinical cases. The majority of isolates belonged to the phylogroups B2 and D and encoded polysaccharide capsules. In line with previous studies, our bGWAS identified papGII to be associated with bacteraemia. In a generalised linear model correcting for patient characteristics, papGII was substantiated as a major contributor to invasive infection. Further, an independent cohort of 1,657 urine samples was PCR screened for papGII carrying E. coli, confirming the increased relative frequency of papGII+ strains to cause invasive infection. This study builds on previous work linking papGII with invasive infection by showing that it is a patient-independent risk factor that has diagnostic potential.

The authors have declared no competing interest.

This study was supported by the two Cantons of Basel through a D-BSSE-Uni-Basel Personalised Medicine grant from the ETH Zurich (PMB-03-17, A.C. and A.E.) and a Doc.Mobility fellowship by the Swiss National Science Foundation (P1BSP3-184342, A.C.).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The collection and analysis of strains and patient data was approved by the "Ethikkommission Nordwest- und Zentralschweiz" (EKNZ) (BASEC-Nr. 2019-00748).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The raw reads acquired for this study have been submitted to SRA and are publicly available (Project Accession PRJEB55855). The MALDI-TOF mass spectra acquired for this study can be accessed via the Open Science Foundation (https://osf.io/vmqc5/). All code which was used to visualise bacterial data analysed in this study is available on GitHub (https://github.com/acuenod111/UPEC).

https://osf.io/vmqc5/