HlyF, an underestimated virulence factor of uropathogenic Escherichia coli

Camille V Chagneau; Delphine Payros; Audrey Goman; Cécile Goursat; Laure David; Miki Okuno; Pierre-Jean Bordignon; Carine Séguy; Clémence Massip; Priscilla Branchu; Yoshitoshi Ogura; Jean-Philippe Nougayrède; Marc Marenda; Eric Oswald

doi:10.1016/j.cmi.2023.07.024

HlyF, an underestimated virulence factor of uropathogenic Escherichia coli

Clin Microbiol Infect. 2023 Jul 31:S1198-743X(23)00352-X. doi: 10.1016/j.cmi.2023.07.024. Online ahead of print.

Affiliations

¹ Digestive Health Research Institute (IRSD), National Institute of Health and Medical Research (INSERM), Université de Toulouse Paul Sabatier, National Research Institute for Agriculture, Food and the Environment (INRAE), National Veterinary School of Toulouse (ENVT), Toulouse, France; Service de Bactériologie-Hygiène, Univerity Hospital of Toulouse, Hôpital Purpan, Toulouse, France.
² Digestive Health Research Institute (IRSD), National Institute of Health and Medical Research (INSERM), Université de Toulouse Paul Sabatier, National Research Institute for Agriculture, Food and the Environment (INRAE), National Veterinary School of Toulouse (ENVT), Toulouse, France.
³ Division of Microbiology, Department of Infectious Medicine, Kurume University School of Medicine, Kurume, Japan.
⁴ Melbourne Veterinary School, Faculty of Science, University of Melbourne, Melbourne, Australia.
⁵ Digestive Health Research Institute (IRSD), National Institute of Health and Medical Research (INSERM), Université de Toulouse Paul Sabatier, National Research Institute for Agriculture, Food and the Environment (INRAE), National Veterinary School of Toulouse (ENVT), Toulouse, France; Service de Bactériologie-Hygiène, Univerity Hospital of Toulouse, Hôpital Purpan, Toulouse, France. Electronic address: eric.oswald@inserm.fr.

PMID: 37532127
DOI: 10.1016/j.cmi.2023.07.024

Abstract

Objectives: Urinary tract infections (UTIs) are primarily caused by uropathogenic Escherichia coli (UPEC). This study aims to elucidate the role of the virulence factor HlyF in the epidemiology and pathophysiology of UTIs and investigate the dissemination of plasmids carrying the hlyF gene.

Methods: An epidemiological analysis was conducted on a representative collection of 225 UPEC strains isolated from community-acquired infections. Selected hlyF+ strains were fully sequenced using a combination of Illumina and Nanopore technologies. To investigate the impact of HlyF, a murine model of UTI was utilized to compare clinical signs, bacterial loads in the bladder, kidney, and spleen, onset of bacteraemia, and inflammation through cytokine quantification among wild-type hlyF+ strains, isogenic mutants, and complemented mutants.

Results: Our findings demonstrate that 20% of UPEC encode the HlyF protein. These hlyF+ UPEC strains exhibited enhanced virulence, frequently leading to pyelonephritis accompanied by bloodstream infections. Unlike typical UPEC strains, hlyF+ UPEC strains demonstrate a broader phylogroup distribution and possess a unique array of virulence factors and antimicrobial resistance genes, primarily carried by ColV-like plasmids. In the murine UTI model, expression of HlyF was linked to the UPECs' capacity to induce urosepsis and elicit an exacerbated inflammatory response, setting them apart from typical UPEC strains.

Discussion: Overall, our results strongly support the notion that HlyF serves as a significant virulence factor for UPECs, and the dissemination of ColV-like plasmids encoding HlyF warrants further investigation.

Keywords: ColV plasmids; HlyF; Urinary tract infections; Uropathogenic E. coli.