A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition

Stefan E Heiden,Nils-Olaf Hübner,Axel Kramer,Claus-Dieter Heidecke,Jürgen A Bohnert,Sören Gatermann,Veronika Balau,Tim Eckmanns,Katharina Schaufler,Wolfgang Gierer,Elias Eger,Stephan Schaefer,Karsten Becker,Sebastian Guenther

doi:10.1186/s13073-020-00814-6

Abstract

BackgroundAntibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. The K. pneumoniae sequence type (ST) 307 lineage has appeared in several different parts of the world after first being described in Europe in 2008. From June to October 2019, we recorded an outbreak of an extensively drug-resistant ST307 lineage in four medical facilities in north-eastern Germany.MethodsHere, we investigated these isolates and those from subsequent cases in the same facilities. We performed whole-genome sequencing to study phylogenetics, microevolution, and plasmid transmission, as well as phenotypic experiments including growth curves, hypermucoviscosity, siderophore secretion, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance for an in-depth characterization of this outbreak clone.ResultsPhylogenetics suggest a homogenous phylogram with several sub-clades containing either isolates from only one patient or isolates originating from different patients, suggesting inter-patient transmission. We identified three large resistance plasmids, carrying either NDM-1, CTX-M-15, or OXA-48, which K. pneumoniae ST307 likely donated to other K. pneumoniae isolates of different STs and even other bacterial species (e.g., Enterobacter cloacae) within the clinical settings. Several chromosomally and plasmid-encoded, hypervirulence-associated virulence factors (e.g., yersiniabactin, metabolite transporter, aerobactin, and heavy metal resistance genes) were identified in addition. While growth, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance were comparable to several control strains, results from siderophore secretion and hypermucoviscosity experiments revealed superiority of the ST307 clone, similar to an archetypical, hypervirulent K. pneumoniae strain (hvKP1).ConclusionsThe combination of extensive drug resistance and virulence, partly conferred through a “mosaic” plasmid carrying both antibiotic resistance and hypervirulence-associated features, demonstrates serious public health implications.

Highlights

Antibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages
Genomic analysis and phylogeny The Extensively drug-resistant (XDR) K. pneumoniae outbreak clone was first detected at the University Medicine Greifswald on June 25, 2019 (Additional file 2: Table S1), following bacterial screening of a tracheal secretion sample [19]
We focused mainly on the phylogenetics and phenotypes of the ST307 outbreak but included accessory and non-ST307 genomes to investigate transmission of resistance plasmids within the bacterial species and to others

Summary

Introduction

Antibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR), “classic” K. pneumoniae (cKp) has been mainly driven by the dissemination of high-risk clonal lineages and constitutes a major global public health problem [3]. The majority of cKp strains cause infection in immunocompromised patients in healthcare settings and have demonstrated the ability to acquire antibiotic resistance elements. In addition to this cKp, a second pathotype termed hypervirulent K. pneumoniae (hvKp) is currently circulating, in Asia but with increasing reports from other countries [2, 4]. A recent study identified potential biomarkers including peg-344, iroB, iucA, plasmid-borne rmpA and rmpA2 genes, and high siderophore production in hvKp to accurately differentiate the two pathotypes [8]

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