Within patient genetic diversity of blaKPC harboring Klebsiella pneumoniae in a Colombian hospital and identification of a new NTEKPC platform

Abstract

Resistance to carbapenems in Klebsiellapneumoniae has been mostly related with the worldwide dissemination of KPC, largely due to the pandemic clones belonging to the complex clonal (CC) 258. To unravel blaKPC post-endemic clinical impact, here we describe clinical characteristics of 68 patients from a high complexity hospital, and the molecular and genetic characteristics of their 139 blaKPC—K.pneumoniae (KPC-Kp) isolates. Of the 26 patients that presented relapses or reinfections, 16 had changes in the resistance profiles of the isolates recovered from the recurrent episodes. In respect to the genetic diversity of KPC-Kp isolates, PFGE revealed 45 different clonal complexes (CC). MLST for 12 representative clones showed ST258 was present in the most frequent CC (23.0%), however, remaining 11 representative clones belonged to non-CC258 STs (77.0%). Interestingly, 16 patients presented within-patient genetic diversity of KPC-Kp clones. In one of these, three unrelated KPC-Kp clones (ST258, ST504, and ST846) and a blaKPC—K.variicola isolate (ST182) were identified. For this patient, complete genome sequence of one representative isolate of each clone was determined. In K.pneumoniae isolates blaKPC was mobilized by two Tn3-like unrelated platforms: Tn4401b (ST258) and Tn6454 (ST504 and ST846), a new NTEKPC-IIe transposon for first time characterized also determined in the K.variicola isolate of this study. Genome analysis showed these transposons were harbored in different unrelated but previously reported plasmids and in the chromosome of a K.pneumoniae (for Tn4401b). In conclusion, in the blaKPC post-endemic dissemination in Colombia, different KPC-Kp clones (mostly non-CC258) have emerged due to integration of the single blaKPC gene in new genetic platforms. This work also shows the intra-patient resistant and genetic diversity of KPC-Kp isolates. This circulation dynamic could impact the effectiveness of long-term treatments.

Population genomics, resistance, pathogenic potential, and mobile genetic elements of carbapenem-resistantKlebsiella pneumoniaecausing infections in Chile

“…Conversely, in this study, pVA32-58 and related conjugative plasmids (IncN) from ST25, ST11, and ST505 isolates, had the bla KPC-2 gene in the NTE KPC -IIe genetic environment, which recently emerged in Chile in an ST11 K. pneumoniae (and other Enterobacteriaceae), and in K. variicola in Colombia [39,40]. Moreover, pVA172-90 was a new variant with additional resistance genes, including bla CTX-M-2 .…”

“…Both platforms were described in a previous study in Chile [47], with the predominance of the so-called Argentinian variant 1a [59] (NTEKPC-IIa) in non-conjugative plasmids from ST11, ST29, and ST1161 Kp . Conversely, in this study, pVA32-58 and related conjugative plasmids (IncN) from ST25, ST11, and ST505 isolates, had the bla KPC-2 gene in the NTEKPC-IIe genetic environment, which recently emerged in Chile in an ST11 K. pneumoniae (and other Enterobacteriaceae) , and in K. variicola in Colombia [39,40]. Moreover, pVA172-90 was a new variant with additional resistance genes, including bla CTX-M-2.…”

“…Additionally, the KPC-2 plasmids pVA172-90, pVA32-58, pVA681-58, and pVA684-37 (IncN) were ~100% identical, except for the former showing additional segments. The bla KPC-2 gene was found in the NTE KPC -IIe genetic environment (Supplementary Figure 5A), first identified in IncN plasmids from a recent Chilean outbreak of carbapenem-resistant bacteria (e.g., pKpn-3; MT949189.1)[39] and in p33Kva16-KPC and pEC881_KPC from Colombian E. coli and K. variicola isolates[40], showing high identity with pVA681-58 and related plasmids (Supplementary Figure 5B). These KPC plasmids included a class-I integron carrying AAC(6’)-Ib-cr6, arr-3, dfrA27 , and aadA16 , and a region encoding QnrB6, QacEDelta1, and Sul1.…”

Worldwide Dissemination of blaKPC Gene by Novel Mobilization Platforms in Pseudomonas aeruginosa: A Systematic Review

“…Despite the high incidence in NTE KPC reports, it is still not clear whether these genetic structures can be mobilized independently or whether their successful dissemination is due to the involvement of various plasmids, so further analysis of these platforms is warranted. The NTE KPC -IIe is the only element of this kind that has shown defined inverted repeats (IRs) in addition to presenting direct repeats as an indication of its transposition [ 85 ].…”

Genomic characterization of two carbapenem-resistant Serratia marcescens isolates causing bacteremia: Emergence of KPC-2-encoding IncR plasmids

“…The global spread of the resistance of Enterobacterales to many antibiotics, seriously affecting the treatment of infections, has become a major public issue ( Hu et al., 2018 ; Dong et al., 2018 ; Dong et al., 2018 ; Zheng et al., 2020 ). The major plasmid types carrying bla KPC-2 published included IncFII, IncF, IncP-6, IncN, ColRNAI, and IncI2 ( Xu et al., 2018 ; Hu et al., 2019 ; Xiaoliang et al., 2019 ; Abril et al., 2021 ; Peng et al., 2022 ). To the best of our knowledge, this is the first time that bla KPC-2 genes have been found to be carried by IncR plasmid in S. marcescens isolates from bacteremia.…”