Bacterial genome-wide association study substantiates papGII of Escherichia coli as a major risk factor for urosepsis

Genome Medicine

Research

Jessica Agnetti¹  Denise Wälchli¹  Adrian Egli²  Helena M. B. Seth-Smith³  Tim Roloff³  Aline Cuénod⁴  Martin Siegemund⁵  Jacob Moran-Gilad⁶  Timothy G. Keys⁷  Stefano Bassetti⁸  Christian H. Nickel⁹  Sarah Tschudin-Sutter^1,10  Dimitri Shcherbakov^1,11  Rashid Akbergenov^1,11  Valentin Pflüger^1,12  Nicholas R. Thomson^1,13 

[1] Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland;Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland;Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland;Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland;Institute for Medical Microbiology, University of Zurich, Zurich, Switzerland;Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland;Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland;Institute for Medical Microbiology, University of Zurich, Zurich, Switzerland;Swiss Institute for Bioinformatics, Basel, Switzerland;Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland;Clinical Bacteriology and Mycology, University Hospital Basel, Basel, Switzerland;Parasites and Microbes, Wellcome Trust Sanger Institute, Hinxton, UK;Institute for Medical Microbiology, University of Zurich, Zurich, Switzerland;Department of Microbiology and Immunology, McGill University, Montréal, Canada;Department of Clinical Research, University of Basel, Basel, Switzerland;Intensive Care Unit, University Hospital Basel, Basel, Switzerland;Department of Health Policy and Management, School of Public Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Be’er Sheva, Israel;Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland;Division of Internal Medicine, University Hospital Basel, Basel, Switzerland;Emergency Department, University Hospital Basel and University of Basel, Basel, Switzerland;Infectious Diseases and Hospital Epidemiology, University Hospital Basel and University of Basel, Basel, Switzerland;Department of Clinical Research, University of Basel, Basel, Switzerland;Institute for Medical Microbiology, University of Zurich, Zurich, Switzerland;Mabritec AG, Riehen, Switzerland;Parasites and Microbes, Wellcome Trust Sanger Institute, Hinxton, UK;Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, UK;

关键词: Escherichia coli;    Urinary tract infection;    Invasiveness;    bGWAS;    papGII;   

DOI  :  10.1186/s13073-023-01243-x

 received in 2023-06-06, accepted in 2023-10-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundUrinary tract infections (UTIs) are among the most common bacterial infections worldwide, often caused by uropathogenic Escherichia coli. Multiple bacterial virulence factors or patient characteristics have been linked separately to progressive, more invasive infections. In this study, we aim to identify pathogen- and patient-specific factors that drive the progression to urosepsis by jointly analysing bacterial and host characteristics.MethodsWe analysed 1076 E. coli strains isolated from 825 clinical cases with UTI and/or bacteraemia by whole-genome sequencing (Illumina). Sequence types (STs) were determined via srst2 and capsule loci via fastKaptive. We compared the isolates from urine and blood to confirm clonality. Furthermore, we performed a bacterial genome-wide association study (bGWAS) (pyseer) using bacteraemia as the primary clinical outcome. Clinical data were collected by an electronic patient chart review. We concurrently analysed the association of the most significant bGWAS hit and important patient characteristics with the clinical endpoint bacteraemia using a generalised linear model (GLM). Finally, we designed qPCR primers and probes to detect papGII-positive E. coli strains and prospectively screened E. coli from urine samples (n = 1657) at two healthcare centres.ResultsOur patient cohort had a median age of 75.3 years (range: 18.00–103.1) and was predominantly female (574/825, 69.6%). The bacterial phylogroups B2 (60.6%; 500/825) and D (16.6%; 137/825), which are associated with extraintestinal infections, represent the majority of the strains in our collection, many of which encode a polysaccharide capsule (63.4%; 525/825). The most frequently observed STs were ST131 (12.7%; 105/825), ST69 (11.0%; 91/825), and ST73 (10.2%; 84/825). Of interest, in 12.3% (13/106) of cases, the E. coli pairs in urine and blood were only distantly related. In line with previous bGWAS studies, we identified the gene papGII (p-value < 0.001), which encodes the adhesin subunit of the E. coli P-pilus, to be associated with ‘bacteraemia’ in our bGWAS. In our GLM, correcting for patient characteristics, papGII remained highly significant (odds ratio = 5.27, 95% confidence interval = [3.48, 7.97], p-value < 0.001). An independent cohort of cases which we screened for papGII-carrying E. coli at two healthcare centres further confirmed the increased relative frequency of papGII-positive strains causing invasive infection, compared to papGII-negative strains (p-value = 0.033, chi-squared test).ConclusionsThis study builds on previous work linking papGII with invasive infection by showing that it is a major risk factor for progression from UTI to bacteraemia that has diagnostic potential.

【 授权许可】

CC BY   
© The Author(s) 2023

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