Whole-Genome Sequencing of Human ClinicalKlebsiella pneumoniaeIsolates Reveals Misidentification and Misunderstandings ofKlebsiella pneumoniae,Klebsiella variicola, andKlebsiella quasipneumoniae
ABSTRACTKlebsiella pneumoniaeis a major threat to public health, causing significant morbidity and mortality worldwide. The emergence of highly drug-resistant strains is particularly concerning. There has been a recognition and division ofKlebsiella pneumoniaeinto three distinct phylogenetic groups:Klebsiella pneumoniae,Klebsiella variicola, andKlebsiella quasipneumoniae.K. variicolaandK. quasipneumoniaehave often been described as opportunistic pathogens that have less virulence in humans thanK. pneumoniaedoes. We recently sequenced the genomes of 1,777 extended-spectrum-beta-lactamase (ESBL)-producingK. pneumoniaeisolates recovered from human infections and discovered that 28 strains were phylogenetically related toK.variicolaandK. quasipneumoniae. Whole-genome sequencing of 95 additional non-ESBL-producingK. pneumoniaeisolates recovered from patients found 12K. quasipneumoniaestrains. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) analysis initially identified all patient isolates asK. pneumoniae, suggesting a potential pitfall in conventional clinical microbiology laboratory identification methods. Whole-genome sequence analysis revealed extensive sharing of core gene content and plasmid replicons among theKlebsiellaspecies. For the first time, strains of bothK. variicolaandK. quasipneumoniaewere found to carry theKlebsiella pneumoniaecarbapenemase (KPC) gene, while anotherK. variicolastrain was found to carry the New Delhi metallo-beta-lactamase 1 (NDM-1) gene.K. variicolaandK. quasipneumoniaeinfections were not less virulent thanK. pneumoniaeinfections, as assessed by in-hospital mortality and infection type. We also discovered evidence of homologous recombination in oneK. variicolastrain, as well as one strain from a novelKlebsiellaspecies, which challenge the current understanding of interrelationships between clades ofKlebsiella.IMPORTANCEKlebsiella pneumoniaeis a serious human pathogen associated with resistance to multiple antibiotics and high mortality.K. variicolaandK. quasipneumoniaeare closely related organisms that are generally considered to be less-virulent opportunistic pathogens. We used a large, comprehensive, population-based strain collection and whole-genome sequencing to investigate infections caused by these organisms in our hospital system. We discovered thatK. variicolaandK. quasipneumoniaeisolates are often misidentified asK. pneumoniaeby routine clinical microbiology diagnostics and frequently cause severe life-threatening infections similar toK. pneumoniae. The presence of KPC inK. variicolaandK. quasipneumoniaestrains as well as NDM-1 metallo-beta-lactamase in oneK. variicolastrain is particularly concerning because these genes confer resistance to many different beta-lactam antibiotics. The sharing of plasmids, as well as evidence of homologous recombination, between these three species ofKlebsiellais cause for additional concern.