Evolution of Outbreak-Causing Carbapenem-Resistant Klebsiella pneumoniae ST258 at a Tertiary Care Hospital over 8 Years

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains belonging to sequence type 258 (ST258) are frequent causes of hospital-associated outbreaks and are a major contributor to the spread of carbapenemases. This genetic lineage emerged several decades ago and remains a major global health care challenge. In this study, genomic epidemiology was used to investigate the emergence, evolution, and persistence of ST258 carbapenem-resistant K. pneumoniae outbreak-causing lineages at a large tertiary care hospital over 8 years. A time-based phylogenetic analysis of 136 ST258 isolates demonstrated the succession of multiple genetically distinct ST258 sublineages over the 8-year period. Ongoing genomic surveillance identified the emergence and persistence of several distinct clonal ST258 populations. Patterns of multidrug resistance determinants and plasmid replicons were consistent with continued evolution and persistence of these populations. Five ST258 outbreaks were documented, including three that were caused by the same clonal lineage. Mutations in genes encoding effectors of biofilm production and iron acquisition were identified among persistent clones. Two emergent lineages bearing K. pneumoniae integrative conjugative element 10 (ICEKp10) and harboring yersiniabactin and colibactin virulence factors were identified. The results show how distinct ST258 subpopulations have evolved and persisted within the same hospital over nearly a decade. IMPORTANCE The carbapenem class of antibiotics is invaluable for the treatment of selected multidrug-resistant Gram-negative pathogens. The continued transmission of carbapenem-resistant bacteria such as ST258 K. pneumoniae is of serious global public health concern, as treatment options for these infections are limited. This genomic epidemiologic investigation traced the natural history of ST258 K. pneumoniae in a single health care setting over nearly a decade. We found that distinct ST258 subpopulations have caused both device-associated and ward-associated outbreaks, and some of these populations remain endemic within our hospital to the present day. The finding of virulence determinants among emergent ST258 clones supports the idea of convergent evolution of drug-resistant and virulent CRKP strains and highlights the need for continued surveillance, prevention, and control efforts to address emergent and evolving ST258 populations in the health care setting.

Horizontally Acquired Homologs of Xenogeneic Silencers: Modulators of Gene Expression Encoded by Plasmids, Phages and Genomic Islands

“…This feature agrees with what has been reported for plasmids and actinobacteriophages that encode homologs of H-NS and Lsr2, respectively, which have a lower GC content compared with those which do not encode an XS homolog [63]. The low GC of the EARL islands and its narrow range of variability (35.7-39.2%) could be the result of their relatively rapid spread within Enterobacteriaceae, an idea supported by the fact that ROD21 can be transferred by conjugation [106] and that the ICEKp258.2 island from K. pneumoniae ST258, which may represent an early member of the SpnT/type-3 R-M-encoding clade within the EARL phylogeny [50], was acquired by this sequence type approximately 20-25 years ago [120][121][122]. Since the XSs show preference for AT-rich DNA, we speculate that these elements have a selective pressure to acquire genes encoding factors that could interact with the silencing effectors from the host cell in order to relieve silencing and provide the opportunity to be incorporated in the host regulatory network.…”

Epidemiology of β-Lactamase-Producing Pathogens

“…One study reported that the transmission rate of ESBL-producing organisms was 2-fold higher from patients colonized with K. pneumoniae than from those colonized with E. coli (335). Large-scale nosocomial outbreaks have been caused by highly virulent and transmissible isolates of ESBL-and carbapenemase-producing strains, such as E. coli ST131 and K. pneumoniae ST258 (209,336). Although most outbreaks of ␤-lactamase producing Enterobacteriaceae occur in the ICU or in immunocompromised patients, neonates can also be affected.…”

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

“…While K. pneumoniae sequence type (ST) 258 has been recognized as antibiotic-resistant, high-risk clonal lineage [9], ST307 came into spotlight only more recently [3,10,11]. The first K. pneumoniae ST307 isolates were obtained in the Netherlands in 2008 and Pakistan in 2009, followed by a period of sporadic isolations across Europe, Asia, Africa, and the Americas [11], and originated mostly, but not uniquely, from clinical samples [3,10].…”