Whole-Genome Sequencing of Human Clinical Isolates Reveals Misidentification and Misunderstandings of , , and .

is 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 of into three distinct phylogenetic groups: , , and . and have often been described as opportunistic pathogens that have less virulence in humans than does. We recently sequenced the genomes of 1,777 extended-spectrum-beta-lactamase (ESBL)-producing isolates recovered from human infections and discovered that 28 strains were phylogenetically related to . and . Whole-genome sequencing of 95 additional non-ESBL-producing isolates recovered from patients found 12 strains. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis initially identified all patient isolates as , 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 the species. For the first time, strains of both and were found to carry the carbapenemase (KPC) gene, while another strain was found to carry the New Delhi metallo-beta-lactamase 1 (NDM-1) gene. and infections were not less virulent than . infections, as assessed by in-hospital mortality and infection type. We also discovered evidence of homologous recombination in one strain, as well as one strain from a novel species, which challenge the current understanding of interrelationships between clades of . is a serious human pathogen associated with resistance to multiple antibiotics and high mortality. and are 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 that and isolates are often misidentified as by routine clinical microbiology diagnostics and frequently cause severe life-threatening infections similar to . The presence of KPC in and strains as well as NDM-1 metallo-beta-lactamase in one strain 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 of is cause for additional concern.