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

Abstract

Background 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 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. Methods Here, 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. Results Phylogenetics 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). Conclusions The 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.

Genome-Based Analysis of Klebsiella spp. Isolates from Animals and Food Products in Germany, 2013–2017

“…Distinct hypervirulent strains that have also acquired carbapenemase genes can enter hospitals and spread among patients. This has mainly been described for China but can also occasionally be observed in Central Europe, including in Germany [ 17 ].…”

Circulation of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli of Pandemic Sequence Types 131, 648, and 410 Among Hospitalized Patients, Caregivers, and the Community in Rwanda

“…Interestingly, previous studies suggest that ESBL-plasmid carriage does not ineluctably reduce bacterial fitness, which seems particularly true for specific clonal lineages (McNally et al, 2016;Schaufler et al, 2016a;Ranjan et al, 2018;Monárrez et al, 2019;Schaufler et al, 2019). The combination of MDR with high-level bacterial virulence and fitness leads to the emergence of these pandemic, high-risk clonal lineages and subsequently contributes to treatment failures, increasing morbidity, and mortality (Melzer and Petersen, 2007;Schwaber and Carmeli, 2007;Tumbarello et al, 2007;Beceiro et al, 2013;Schaufler et al, 2019;Heiden et al, 2020a).…”

Finding Order in the Chaos: Outstanding Questions in Klebsiella pneumoniae Pathogenesis

“…Previous studies have thoroughly reviewed reports of convergent MDR-hvKp isolates from 2009 through early 2020, including genetic factors identified in the convergent isolates ( 50 , 51 ). Since these studies were published, there have recently been additional reports of convergence in Asia, North America, Europe, and South America ( 52 – 61 ). Convergence occurs most frequently when mobile genetic elements carrying multiple antibiotic resistance genes (such as those encoding ESBLs and carbapenemases) are acquired by hvKp, or when virulence genes (like rmpA and siderophores), are acquired by MDR-Kp.…”

“…Convergence occurs most frequently when mobile genetic elements carrying multiple antibiotic resistance genes (such as those encoding ESBLs and carbapenemases) are acquired by hvKp, or when virulence genes (like rmpA and siderophores), are acquired by MDR-Kp. The most alarming finding was the recent observation of mosaic plasmids that harbored both antimicrobial resistance and virulence genes in isolates obtained from patients in Norway, the United Kingdom, China, and Germany ( 56 , 60 – 62 ), as these mosaic plasmids could act as a “one stop shop” for the simultaneous transmission of both hypervirulence and antimicrobial resistance phenotypes into cKp strains.…”