Diversity, virulence, and antimicrobial resistance of the KPC-producing Klebsiella pneumoniae ST307 clone

Abstract

The global spread of Klebsiella pneumoniae producing Klebsiella pneumoniae carbapenemase (KPC) has been mainly associated with the dissemination of high-risk clones. In the last decade, hospital outbreaks involving KPC-producing K. pneumoniae have been predominantly attributed to isolates belonging to clonal group (CG) 258. However, results of recent epidemiological analysis indicate that KPC-producing sequence type (ST) 307, is emerging in different parts of the world and is a candidate to become a prevalent high-risk clone in the near future. Here we show that the ST307 genome encodes genetic features that may provide an advantage in adaptation to the hospital environment and the human host. Sequence analysis revealed novel plasmid-located virulence factors, including a cluster for glycogen synthesis. Glycogen production is considered to be one of the possible adaptive responses to long-term survival and growth in environments outside the host. Chromosomally-encoded virulence traits in the clone comprised fimbriae, an integrative conjugative element carrying the yersiniabactin siderophore, and two different capsular loci. Compared with the ST258 clone, capsulated ST307 isolates showed higher resistance to complement-mediated killing. The acquired genetic features identified in the genome of this new emerging clone may contribute to increased persistence of ST307 in the hospital environment and shed light on its potential epidemiological success.

Emergence and rapid global dissemination of CTX-M-15-associated Klebsiella pneumoniae strain ST307

“…Complementing the increasing reports in the literature, our analyses reveal that ST307 is a highly successful MDR clone that shares many traits with ST258, but is closely associated with bla CTX--M--15 rather than bla KPCs . With sufficient exposure ST307 can acquire and disseminate carbapenemases [1][2][3], and likely other clinically important AMR determinants. ST307 appears to be readily transferred between countries and has already become globally disseminated, yet has remained largely unnoticed for almost 20 years.…”

“…For the majority of genomes carrying bla CTX--M--15 (n=88/89) BLASTn confirmed that this gene was located downstream of ISEcp1, which forms a transposon to mobilise bla CTX--M--15 and promotes its expression [23]. Four complete ST307 IncFII K /IncFIB K bla CTX--M--15 plasmids have been published [2], and share an insertion of the ISEcp1/bla CTX--M--15 transposon within Tn3. Read--mapping to pKPN3--307_typeA (accession KY271404) and assembly graph inspections of our bla CTX--M--15 --positive genomes showed that all carried the same ISEcp1/bla CTX--M--15 transposon.…”

“…Unlike those other clones [17,22], all ST307 shared the same capsule (KL107) and O antigen (O2v2) loci. An additional putative capsule synthesis locus (Kp616 genes C2861_20465 to C2861_20520 [2]), which is unlike any known K--locus, was also conserved among ST307 but is rare among the broader Kp population (data not shown). In contrast to the virulence loci, acquired AMR genes were highly prevalent; 93 (97.9%) isolates carried acquired resistance determinants associated with ≥3 drug classes ( Table S2).…”

Antimicrobial resistant Klebsiella pneumoniae carriage and infection in specialized geriatric care wards linked to acquisition in the referring hospital

“…The ST29 and ST323 MDR isolates each 9 harboured 4-6 plasmids (Table S3). Notably, all the acquired AMR genes in these genomes were localized to the same >200 kbp FIB K /FII K plasmid backbone encoded conjugative transfer functions and shared close similarity (>90% coverage and 99% identity) with plasmid pKPN3-307_type A from an Italian K. pneumoniae [21]. However there were some differences in the MDR regions, resulting in different susceptibility profiles ( Figure S2).…”

Genomic epidemiology of a complex, multi-species plasmid-borne blaKPC carbapenemase outbreak in Enterobacterales in the UK, 2009-2014

“…A reference bla KPC plasmid sequence database composed of bla KPC -harbouring contigs/plasmids from long-read sequencing of isolates in this study and all complete bla KPC plasmids from (42-44) (August 2018) was used for bla KPC plasmid typing within this study. To construct this database, all 279/6018 evaluable plasmid sequences carrying bla KPC were first compared using dnadiff (45) to obtain the pairwise similarity between any two plasmid sequences p i and p j .…”