Host and microbial factors in kidney transplant recipients with Escherichia coli acute pyelonephritis or asymptomatic bacteriuria: A prospective study using whole-genome sequencing

Julien Coussement, Maria Angeles Argudín, Amélie Heinrichs, Judith Racapé, Ricardo de Mendonça, Louise Nienhaus, Alain Le Moine, Sandrine Roisin, Magali Dodémont, Frédérique Jacobs, Daniel Abramowicz, Brian D. Johnston, James R. Johnson, Olivier Denis

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background. Urinary tract infection is the most common infection among kidney transplant recipients (KTRs). Many transplant physicians fear that host compromise will allow low-virulence strains to cause pyelonephritis in KTRs, so they often treat asymptomatic bacteriuria with antibiotics. Identification of the host/microbe factors that determine the clinical presentation (i.e. pyelonephritis versus asymptomatic bacteriuria) once an Escherichia coli strain enters a KTRs bladder could inform management decisions. Methods. We prospectively collected all E. coli isolates causing either pyelonephritis or asymptomatic bacteriuria in KTRs at our institution (December 2012–June 2015). Whole-genome sequencing was used to assess bacterial characteristics (carriage of 48 virulence genes and phylogenetic and clonal background). Host parameters were also collected. Results. We analysed 72 bacteriuria episodes in 54 KTRs (53 pyelonephritis, 19 asymptomatic bacteriuria). The pyelonephritis and asymptomatic bacteriuria isolates exhibited a similar total virulence gene count per isolate [median 18 (range 5–33) and 18 (5–30), respectively; P = 0.57] and for individual virulence genes differed significantly only for the prevalence of the pap operon (pyelonephritis 39%,versus asymptomatic bacteriuria 0%; P = 0.002). No other significant between-group differences were apparent for 86 other bacterial and host variables. Conclusions. Our findings suggest that bacterial adherence plays a role in the pathogenesis of pyelonephritis in KTRs despite significantly altered host urinary tract anatomy and weakened immunity. Whether KTRs might benefit from targeted therapies (e.g. vaccination or inhibitors of fimbrial adhesion) has yet to be studied.

Original languageEnglish (US)
Pages (from-to)878-885
Number of pages8
JournalNephrology Dialysis Transplantation
Volume34
Issue number5
DOIs
StatePublished - May 1 2019

Bibliographical note

Funding Information:
This work was supported by research grants ‘Bourse 2014– 2015 de Recherche Clinique du Conseil Médical de l’Hôpital Erasme’ (Belgium), ‘Bourse 2016 de la Fondation Lekime-Ropsy’ (Belgium) and ‘Bourse 2017–2018 du Fonds Erasme pour la Recherche Médicale’ (Belgium) (all to J.C.), and by the Office of Research and Development, United States Department of Veterans Affairs (J.J., B.J.)

Funding Information:
We thank Dr Nicole Stoesser (Oxford, UK) for helping to create the in-house database of virulence factors and Dr Mathew Upton (Plymouth, UK) for sending the E. coli EC958 control strain. We thank Prof. Herman Goossens (Antwerpen, Belgium), Prof. Marc Hazzan (Lille, France) and Dr Laurent Weekers (Li?ge, Belgium), who sent the three additional clinical isolates. We thank our colleagues from Applied Maths (Sint-Martens-Latem, Belgium) for their help regarding BioNumerics. We also thank all our colleagues from the Department of Microbiology who helped with the practical aspects of the study. We thank Dominique Moniot for helping to create Figure 2. Last, we would like to thank Dr David Lebeaux (Paris, France) for providing helpful suggestions during data analysis. The opinions expressed here are strictly those of the authors and are not necessarily those of their respective institutions or the funders. This work was supported by research grants ?Bourse 2014?2015 de Recherche Clinique du Conseil M?dical de l?H?pital Erasme? (Belgium), ?Bourse 2016 de la Fondation Lekime-Ropsy? (Belgium) and ?Bourse 2017?2018 du Fonds Erasme pour la Recherche M?dicale? (Belgium) (all to J.C.), and by the Office of Research and Development, United States Department of Veterans Affairs (J.J., B.J.)

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Keywords

  • ExPEC
  • NGS
  • UPEC
  • Urinary tract infections
  • Virulome

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