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Abstract
ABSTRACTKlebsiella pneumoniae is a human commensal and opportunistic pathogen that has become a leading causative agent of hospital-based infections over the past few decades. The emergence and global expansion of hypervirulent and multidrug-resistant (MDR) clones of K. pneumoniae have been increasingly reported in community-acquired and nosocomial infections. Despite this, the population genomics and epidemiology of MDR K. pneumoniae at the national level are still poorly understood. To obtain insights into these, we analyzed a systematic large-scale collection of invasive MDR K. pneumoniae isolates from hospitals across the United Kingdom and Ireland. Using whole-genome phylogenetic analysis, we placed these in the context of previously sequenced K. pneumoniae populations from geographically diverse countries and identified their virulence and drug resistance determinants. Our results demonstrate that United Kingdom and Ireland MDR isolates are a highly diverse population drawn from across the global phylogenetic tree of K. pneumoniae and represent multiple recent international introductions that are mainly from Europe but in some cases from more distant countries. In addition, we identified novel genetic determinants underlying resistance to beta-lactams, gentamicin, ciprofloxacin, and tetracyclines, indicating that both increased virulence and resistance have emerged independently multiple times throughout the population. Our data show that MDR K. pneumoniae isolates in the United Kingdom and Ireland have multiple distinct origins and appear to be part of a globally circulating K. pneumoniae population.
Highlights
Klebsiella pneumoniae is a human commensal and opportunistic pathogen that has become a leading causative agent of hospital-based infections over the past few decades
Our results indicate that the K. pneumoniae population is highly diverse and that, in some cases, resistant strains appear to have spread across the country over a few years
The resulting combined phylogenetic tree revealed that the United Kingdom and Ireland MDR isolates reside on multiple branches of the global tree but some clades are composed mainly of United Kingdom samples (Fig. 1A)
Summary
Klebsiella pneumoniae is a human commensal and opportunistic pathogen that has become a leading causative agent of hospital-based infections over the past few decades. Our results demonstrate that United Kingdom and Ireland MDR isolates are a highly diverse population drawn from across the global phylogenetic tree of K. pneumoniae and represent multiple recent international introductions that are mainly from Europe but in some cases from more distant countries. Holt et al [4] generated a global phylogeny of K. pneumoniae isolates from environmental and hospital sources and demonstrated that in the light of detailed phylogenetic evidence, the K. pneumoniae species complex may be split into three distinct species referred to as K. pneumoniae (KpI), K. quasipneumoniae (KpII), and K. variicola (KpIII), all of which are known to cause infections in humans [13, 14] and each of which contains a high level of diversity. The investigations commonly identify multidrug-resistant (MDR) strains, in particular, carbapenem-resistant strains
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