Abstract
ObjectivesEscherichia coli is the leading cause of bacteraemia. In an era of emerging multi-drug-resistant strains, development of effective preventative strategies will be informed by knowledge of strain diversity associated with specific infective syndromes/patient groups. We hypothesised that the number of virulence factor (VF) genes amongst bacteraemia isolates from neutropaenic patients would be lower than isolates from immunocompetent patients. MethodsImmunocompetent and neutropaenic adults with E. coli bacteraemia were recruited prospectively and the source of bacteraemia determined. VF gene profiles were established in silico following whole genome sequencing. ResultsIsolates from individual patients were monoclonal. Strains from immunocompetent patients with urinary tract infective foci (UTIF) harboured more VF genes (median number of VF genes 16, range 8–24) than isolates from both immunocompetent patients with non-UTIF (10, 2–22, p = 0.0058) and neutropaenic patients with unknown focus of infection (NPUFI) (8, 3–13, p < 0.0001). Number of VF genes (OR 1.21, 95% CIs 1.01–1.46, p = 0.039) and urinary catheter/recurrent urinary tract infection (OR 12.82, 95% CIs 1.24–132.65, p = 0.032) were independent predictors of bacteraemia secondary to UTIF vs. non-UTIF in immunocompetent patients. papA, papC, papE/F, papG, agn43, tia, iut, fyuA, kpsM and sat were significantly more prevalent amongst UTIF- vs non-UTIF-originating isolates amongst immunocompetent patients, while papC, papE/F, papG, agn43, tia, fyuA, hlyA, usp and clb were significantly more prevalent amongst UTIF- vs NPUFI-associated isolates. ConclusionsBacteraemia-associated E. coli strains originating from UTIF have distinct VF gene profiles from strains associated with non-UTIF- and NPUFI. This diversity must be addressed in the design of future vaccines to ensure adequate coverage of strains responsible for site-specific disease.
Highlights
Extra-intestinal pathogenic E. coli (ExPEC) are the leading cause of bacteraemia world-wide and are associated with urinary tract, hepatobiliary/gastro-intestinal tract, skin/soft tissue and respiratory tract infections, as well as neonatal meningitis and febrile neutropaenia.[1]
Analysis of Whole genome sequencing (WGS) data demonstrated that 15/16 linked urinary isolates from patients with microbiologically-proven urinary tract infection (UTI) shared the same ST as the bacteraemia strain
Bacteraemia-associated E. coli strains originating from urinary tract infective foci (UTIF) harboured significantly more virulence factor (VF) genes than non-UTIFand neutropaenic patients with unknown focus of infection (NPUFI)-associated strains
Summary
Extra-intestinal pathogenic E. coli (ExPEC) are the leading cause of bacteraemia world-wide and are associated with urinary tract, hepatobiliary/gastro-intestinal tract, skin/soft tissue and respiratory tract infections, as well as neonatal meningitis and febrile neutropaenia.[1]. Hesp et al / Journal of Infection 77 (2018) 534–543 hesion siderophore gene, and the ibeA protectin invasin gene)[1,6] and neonatal meningitis (kps capsule gene, ompA and ibe protectin/invasin genes, fimH adhesin gene, and cnf[1] toxin gene).[1,7] A broad range of STs can cause disease but 50–70% of diseaseassociated isolates belong to STs 69, 73, 95, 127 and 131.8
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