Whole genome sequencing to decipher the virulence phenotype of hypervirulent Klebsiella pneumoniae responsible for liver

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Whole genome sequencing to decipher the virulence phenotype of hypervirulent Klebsiella pneumoniae responsible for liver abscess, Marseille, France Sophie Alexandra Baron 1,2 & Léa-Marie Pascale 1,2 & Matthieu Million 1,2 & Antoine Briantais 3 & Jean-Marc Durand 3 & Linda Hadjadj 1,2 & Jean-Marc Rolain 1,2,4 Received: 18 August 2020 / Accepted: 21 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract We described three clinical cases of pyogenic liver abscess caused by hypervirulent Klebsiella pneumoniae (hvKp) successfully treated by prolonged antibiotherapy, in which one case was complicated by endophthalmitis. Whole genome sequencing helped to confirm the diagnosis of these hvKp strains, which belong to clonal complexes CC86 and CC23 and carried hvKp-associated genes (magA and/or rmpA). This syndrome is increasingly reported in France and Europe and raises questions about the source of infection. Keywords Liver abscess . Klebsiella pneumoniae . Hypervirulent . ST86 . ST23

Introduction In the 1980s, primary liver abscess syndrome caused by hypervirulent Klebsiella pneumoniae (hvKp) emerged in Asia [1]. The CG23 clone associated with a K1 capsular type was the main clone of hvKp responsible for this syndrome [2, 3]. However, the emergence of this clone dates back to the late nineteenth century and suggests worldwide dissemination [4]. Other non-K1 serotype clones responsible for liver abscess include the CG65 (including the ST65 and the ST375) and the CG86 clones, which are mainly from serotype K2. These infections are often associated with severe clinical manifestations and a bad prognosis, thus contrasting with the high-level

* Jean-Marc Rolain [email protected] 1

IRD, APHM, MEPHI, Faculté de Médecine et de Pharmacie, Aix Marseille Univ, 19-21 boulevard Jean Moulin, 13385, Marseille, CEDEX 05, France

2

IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, 13385, Marseille, CEDEX 05, France

3

Service de Médecine Interne, Hôpital La Timone, APHM, Marseille, France

4

IRD, APHM, MEPHI, IHU Méditerranée Infection, Faculté de Médecine et de Pharmacie, Aix Marseille Univ, 19-21 boulevard Jean Moulin, 13385, Marseille, CEDEX 05, France

antibiotic susceptibility of the strains [5, 6]. Several factors have been linked to hypervirulent clones such as a positive string test, the virulence plasmid pLVKP, the mucoviscosityassociated gene A (magA), rmpA, or siderophore such as aerobactin [1]. However, the definition of hvKp is not clear in the literature and varies from studies, as virulence factors are inconsistently present in hvKp and can also been found in other non-hypervirulent clones. We report here three cases of patients hospitalized in Marseille, France, with a K. pneumoniae responsible for liver abscesses, and whole genome sequencing (WGS) helped to characterize these clones.

Cases presentation The first patient was a 42-year-old man who originated from Algeria was admitted to the hospital for a fever associated with nausea, diarrhea, and asthenia