A Small KPC-2-Producing Plasmid in Klebsiella pneumoniae : Implications for Diversified Vehicles of Carbapenem Resistance

Abstract

A rare ST437 isolate termed K186 was clinically determined which was unlike ST11, the dominant sequence type of CRKP. Whole-genome sequencing enabled us to discover three distinct resistance plasmids, namely, pK186_1, pK186_2, and pK186_KPC. Among them, pK186_KPC appears as a unique plasmid ~26 kb in size, much smaller than the prevalent forms (~120 to ~170 kb). The convergence of hypervirulence to carbapenem-resistant K. pneumoniae (CRKP) in a highly transmissible ST11 clone poses a great challenge to public health and anti-infection therapy. Recently, we revealed that an expanding repertoire of diversified KPC-2-producing plasmids occurs in these high-risk clones. Here, we report a clinical case infected with a rare isolate of ST437 CRKP, K186, which exhibited KPC-2 production. Apart from its 5,322,657-bp long chromosome, whole-genome sequencing of strain K186 elucidated three distinct resistance plasmids (designated pK186_1, pK186_2, and pK186_KPC, respectively). Unlike the prevalently larger form of KPC-2-producing plasmids (~120 to ~170 kb) earlier we observed, pK186_KPC is an IncN-type, small plasmid of 26,012bp in length. Combined with the colinear alignment of plasmid genome, the analyses of insertion sequences further suggested that this carbapenem-resistant pK186_KPC might arise from the cointegration of its ancestral IncN and IncFII plasmids, exclusively relying on IS 26 -based transposition events. Taken together, the result represents an unusual example of bla KPC-2 -bearing small plasmids, and highlights an ongoing arsenal of diversified carriers benefiting the transferability of KPC-2 carbapenem resistance. IMPORTANCE A rare ST437 isolate termed K186 was clinically determined which was unlike ST11, the dominant sequence type of CRKP. Whole-genome sequencing enabled us to discover three distinct resistance plasmids, namely, pK186_1, pK186_2, and pK186_KPC. Among them, pK186_KPC appears as a unique plasmid ~26 kb in size, much smaller than the prevalent forms (~120 to ~170 kb). Intriguingly, genetic analysis suggests that it might originate from Proteus mirabilis . This result constitutes an additional example of differentiated plasmid vehicles dedicated to the emergence and dissemination of KPC-2 carbapenem resistance.