Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding

Abstract

Klebsiella pneumoniae carbapenemases (KPCs) were first identified in 1996 in the USA. Since then, regional outbreaks of KPC-producing K. pneumoniae (KPC-Kp) have occurred in the USA, and have spread internationally. Dissemination of blaKPC involves both horizontal transfer of blaKPC genes and plasmids, and clonal spread. Of epidemiological significance, the international spread of KPC-producing K. pneumoniae is primarily associated with a single multilocus sequence type (ST), ST258, and its related variants. However, the molecular factors contributing to the success of ST258 largely remain unclear. In this review, we discuss the recent progresses in understanding KPC-producing K. pneumoniae that are contributing to our knowledge of plasmid and genome composition and structure among the KPC epidemic clone, and we identify possible factors that influence its epidemiological success.

Keywords: Klebsiella pneumoniae carbapenemase; ST258; carbapenem-resistant.

Figure 1

(A). Population structure of KPC-Kp. The figure represents the population structure of the K. pneumoniae MLST database (http://www.pasteur.fr/mlst) as of April 1, 2014, depicted graphically by eBURST v.3 (http://eburst.mlst.net), and shown in the context of all of the 1,536 STs from 1,924 isolates. KPC-Kp STs are highlighted by a pink halo. (B). Population structure of CG258. The pink shading highlights the STs of CG258-tonB79 cluster.

Figure 2

Mauve plots of thirteen completely sequenced K. pneumoniae genomes. Boxes with identical colors represent local colinear blocks (LCB), indicating homologous DNA regions shared by two or more chromosomes without sequence rearrangements. LCBs indicated below the horizontal black line represent reverse complements of the reference LCB. Red (forward) and blue (reverse) shading denotes shared regions of homology, and the black box line illustrates the cps region in each genome. ST258 isolates (NJST258_1 and _2; CP006923 and CP006918) [24], ST11 isolate ATCC BAA-2146 (CP006659) [73], ST38 isolate MGH 78578 (CP000647) and one ST146 isolate (Kp 342) (CP000964) [74] were from United States; ST11 isolates HS11286 (CP003200) [29] and JM45 (CP006656) were from mainland China; two ST23 K1 isolates (NTUH-K2044 and Kp 1084; AP006725 and CP003785) and one ST86 K2 isolate (CP006648) were from were Taiwan [75, 76]; and ST375 isolate (KCTC 2242; CP002910) was from Korea [77], and one ST442 isolate (Kp13; CP003999) is from Brazil [23]. The left panel is the maximum likelihood tree generated using the SNPs extracted by Mauve.

Figure 3

bla_KPC-harboring genetic elements (Tn4401 and NTE_KPC). Based on the insertion sequence upstream of bla_KPC, NTE_KPC can be divided into three groups: NTE_KPC-I, no insertion [48]; NTE_KPC-II, insertion of Δbla_TEM [48]; and NTE_KPC-III, insertion of Tn5563/IS6100 [78]. NTE_KPC-I can be further classified as -Ia (prototype, pKp048) [48], -Ib (pKPHS2) [29], -Ic (pKp13d) [23] and -Id (pKPC-LKEc) [79] based on the insertion sites of upstream and/or downstream of IS26 and the presence of ISKpn8. NTE_KPC-II can be subgrouped as -IIa (pFP10-1, and bla_KPC-harboring plasmids from strain M9196 and M11180) [49, 80], -IIb (from strain M9884 and M9988) [49], and -IIc (pPA-2) [50], based on the differences of the length of Δbla_TEM and the deletions. Light-blue shading denotes shared regions of homology.

Figure 4

Structures of bla_KPC-harboring plasmids: p12 (IncN), pKpQIL (IncFII_K2), pKp048 (IncFII_K5), pBK15692 (IncI2), pBK30683 (IncFIA), and pKp13d (IncX3).