Abstract
As part of the ongoing studies with clinically relevant Klebsiella spp., we characterized the genomes of three clinical GES-5-positive ST138 strains originally identified as Klebsiella oxytoca. bla OXY gene, average nucleotide identity and phylogenetic analyses showed the strains to be Klebsiella michiganensis. Affiliation of the strains to ST138 led us to demonstrate that the current multi-locus sequence typing scheme for K. oxytoca can be used to distinguish members of this genetically diverse complex of bacteria. The strains encoded the kleboxymycin biosynthetic gene cluster (BGC), previously only found in K. oxytoca strains and one strain of Klebsiella grimontii. The finding of this BGC, associated with antibiotic-associated haemorrhagic colitis, in K. michiganensis led us to carry out a wide-ranging study to determine the prevalence of this BGC in Klebsiella spp. Of 7170 publicly available Klebsiella genome sequences screened, 88 encoded the kleboxymycin BGC. All BGC-positive strains belonged to the K. oxytoca complex, with strains of four (K. oxytoca, K. pasteurii, K. grimontii, K. michiganensis) of the six species of complex found to encode the complete BGC. In addition to being found in K. grimontii strains isolated from preterm infants, the BGC was found in K. oxytoca and K. michiganensis metagenome-assembled genomes recovered from neonates. Detection of the kleboxymycin BGC across the K. oxytoca complex may be of clinical relevance and this cluster should be included in databases characterizing virulence factors, in addition to those characterizing BGCs.
Highlights
Members of the Klebsiella oxytoca complex encode a chromosomal β-lactamase gene (1)
Given that the blaOXY gene has diversified in parallel to housekeeping genes in the K. oxytoca complex, it is likely that the K. oxytoca multi-locus sequence typing (MLST) scheme (8) can be used to speciate all members of this genetically diverse group of bacteria
The three clinical strains characterized had previously been included in a study of outbreak strains encoding GES-5 and CTX-M-15 (9), the first report of GES-5-positive clinical isolates of K. oxytoca ST138 in the UK
Summary
Members of the Klebsiella oxytoca complex encode a chromosomal β-lactamase gene (blaOXY) (1). Differences in the sequence of this gene allowed the establishment of phylogroups (Ko), which correspond to species: K. michiganensis (Ko1, with Ko5 representing a sub-lineage), K. oxytoca (Ko2), K. spallanzanii (Ko3), K. pasteurii (Ko4), K. grimontii (Ko6) and K. huaxiensis (Ko8). All members of the K. oxytoca complex can be differentiated by MALDI-TOF (1), but reference databases currently in routine clinical use lack reference spectra of the different species to allow identification beyond K. oxytoca. Given that the blaOXY gene has diversified in parallel to housekeeping genes in the K. oxytoca complex, it is likely that the K. oxytoca multi-locus sequence typing (MLST) scheme (8) can be used to speciate all members of this genetically diverse group of bacteria
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