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

被引:111
作者
Heiden, Stefan E. [1 ]
Huebner, Nils-Olaf [2 ]
Bohnert, Juergen A. [3 ]
Heidecke, Claus-Dieter [4 ]
Kramer, Axel [5 ]
Balau, Veronika [6 ]
Gierer, Wolfgang [7 ]
Schaefer, Stephan [7 ]
Eckmanns, Tim [8 ]
Gatermann, Soeren [9 ]
Eger, Elias [1 ]
Guenther, Sebastian [10 ]
Becker, Karsten [3 ]
Schaufler, Katharina [1 ]
机构
[1] Univ Greifswald, Inst Pharm Pharmaceut Microbiol, Friedrich Ludwig Jahn Str 17, D-17489 Greifswald, Germany
[2] Univ Med Greifswald, Cent Unit Infect Prevent & Control, Greifswald, Germany
[3] Univ Med Greifswald, Friedrich Loeffler Inst Med Microbiol, Greifswald, Germany
[4] Univ Med Greifswald, Dept Gen Visceral Thorac & Vasc Surg, Greifswald, Germany
[5] Univ Med Greifswald, Inst Hyg & Environm Med, Greifswald, Germany
[6] IMD Lab Greifswald, Inst Med Diagnost, Greifswald, Germany
[7] MVZ Lab Limbach Vorpommern Rugen, Stralsund, Germany
[8] Robert Koch Inst, Dept Infect Dis Epidemiol, Berlin, Germany
[9] Ruhr Univ Bochum, Natl Reference Ctr Multidrug Resistant Gram Negat, Bochum, Germany
[10] Univ Greifswald, Inst Pharm Pharmaceut Biol, Greifswald, Germany
关键词
XDR Klebsiella pneumoniae; Outbreak; Hypervirulence; Plasmid transmission; “ Mosaic” plasmid; ANTIMICROBIAL RESISTANCE; ESCHERICHIA-COLI; SEQUENCE; VIRULENCE; EPIDEMIOLOGY; AEROBACTIN; INFECTION; STRAIN; K2;
D O I
10.1186/s13073-020-00814-6
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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