Clonality and Resistome Analysis of KPC-ProducingKlebsiella pneumoniaeStrain Isolated in Korea Using Whole Genome Sequencing

Abstract

We analyzed the whole genome sequence and resistome of the outbreak Klebsiella pneumoniae strain MP14 and compared it with those of K. pneumoniae carbapenemase- (KPC-) producing isolates that showed high similarity in the NCBI genome database. A KPC-2-producing multidrug-resistant (MDR) K. pneumoniae clinical isolate was obtained from a patient admitted to a Korean hospital in 2011. The strain MP14 was resistant to all tested β-lactams including monobactam, amikacin, levofloxacin, and cotrimoxazole, but susceptible to tigecycline and colistin. Resistome analysis showed the presence of β-lactamase genes including bla KPC-2, bla SHV-11, bla TEM-169, and bla OXA-9. MP14 also possessed aac(6′-)Ib, aadA2, and aph(3′-)Ia as aminoglycoside resistance-encoding genes, mph(A) for macrolides, oqxA and oqxB for quinolone, catA1 for phenicol, sul1 for sulfonamide, and dfrA12 for trimethoprim. Both SNP tree and cgMLST analysis showed the close relatedness with the KPC producers (KPNIH strains) isolated from an outbreak in the USA and colistin-resistant strains isolated in Italy. The plasmid-scaffold genes in plasmids pKpQil, pKpQil-IT, pKPN3, or pKPN-IT were identified in MP14, KPNIH, and Italian strains. The KPC-2-producing MDR K. pneumoniae ST258 stain isolated in Korea was highly clonally related with MDR K. pneumoniae strains from the USA and Italy. Global spread of KPC-producing K. pneumoniae is a worrying phenomenon.

Carbapenemase-Producing Klebsiella pneumoniae, a Key Pathogen Set for Global Nosocomial Dominance

“…This suggests that certain ancestral plasmids are particularly well suited to Enterobacteriaceae, such as K. pneumoniae, and are good candidates for sustaining the presence of bla KPC through multiple independent insertion and transposition events. This is further supported by a recent study in Korea that demonstrated that ancestral plasmids were present among the ST258 isolates found in various geographical regions and were obtained as early as 2002 (87).…”

The Role of Epidemic Resistance Plasmids and International High-Risk Clones in the Spread of Multidrug-Resistant Enterobacteriaceae

“…This suggests that certain ancestral plasmids are particularly well suited to Enterobacteriaceae such as K. pneumoniae and are good candidates for sustaining the presence of bla KPC through multiple independent insertion and transposition events. This is further supported by a recent study from South Korea that demonstrated that ancestral plasmids were present among ST258 isolates from various geographical regions and were obtained as early as 2002 (143).…”

“…A recent study that used next-generation sequencing with long reads examined the contents on plasmids in a single ST258 isolate. Those investigators identified four plasmids containing 24 different resistance genes (142) , and bla TEM-1 ), fluoroquinolone resistance (i.e., oqxA and oqxB), macrolide-lincosamide-streptogramin B resistance (i.e., mphA), chloramphenicol resistance (i.e., catA1), trimethoprim resistance (i.e., dfrA12), and sulfonamide resistance (i.e., sul1) (142,143). ST258 isolates can also decrease the number of porin channels, which leads to nonsusceptibility to additional classes of antimicrobial drugs, leaving clinicians with very limited treatment options (144).…”

Complete Sequence of bla KPC-2 -Harboring Plasmid with a Mosaic of IncN1- and IncN3-Type Plasmids in a Klebsiella pneumoniae Isolate from South Korea

“…The carbapenem resistance of the isolate that we uncovered in this study may not be due to the horizontal transfer of the plasmid and clonal spread because similar plasmids carrying bla KPC-2 have not been reported and because the K. pneumoniae isolate carrying pKPC-DK05 has a novel genotype unknown to produce K. pneumoniae carbapenemase (KPC) (5)(6)(7)(8). Thus, we can speculate that our carbapenemase-producing K. pneumoniae isolate emerged via incorporation of Tn4401 into the prevailing plasmid.…”