Carbapenem Resistance-Encoding and Virulence-Encoding Conjugative Plasmids in Klebsiella pneumoniae

Yang, Xuemei; Dong, Ning; Chan, Edward Wai-Chi; Zhang, Rong; Chen, Sheng

doi:10.1016/j.tim.2020.04.012

Cited by 164 publications

(166 citation statements)

References 85 publications

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“…It was first reported in Israel in 2006, but a retrospective study revealed that it had been carried by a K. pneumoniae isolate from a patient in New York in 2004 [ 41 , 42 , 43 , 44 ]. This plasmid was the first bla KPC -bearing plasmid identified in epidemic ST258 strains, becoming well-known for the early dissemination of KPC-encoding genes [ 25 , 45 , 46 ]. Despite its worldwide spread, pKpQIL-like plasmids were only recently reported in Brazil in K. pneumoniae ST16 [ 25 , 32 , 41 , 43 , 44 , 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…The bla KPC-30 variant shows a single-point mutation compared to bla KPC-2 , leading to one amino acid change (R6H) in the region coding for the signal peptide. In this regard, a high degree of synteny between bla KPC-2 and bla KPC-30 -carrying plasmids was noted and, as matter of fact, highly similar plasmids have often been identified in epidemic strains, such as those belonging to CC258 [ 45 , 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of blaKPC-2, blaKPC-3 and blaKPC-30—Carrying Plasmids in Klebsiella pneumoniae Isolated in a Brazilian Hospital

et al. 2021

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Klebsiella pneumoniae carbapenemase (KPC) actively hydrolyzes carbapenems, antibiotics often used a last-line treatment for multidrug-resistant bacteria. KPC clinical relevance resides in its widespread dissemination. In this work, we report the genomic context of KPC coding genes blaKPC-2, blaKPC-3 and blaKPC-30 in multidrug-resistant Klebsiella pneumoniae isolates from Brazil. Plasmids harboring blaKPC-3 and blaKPC-30 were identified. Fifteen additional carbapenem-resistant K. pneumoniae isolates were selected from the same tertiary hospital, collected over a period of 8 years. Their genomes were sequenced in order to evaluate the prevalence and dissemination of blaKPC–harboring plasmids. We found that blaKPC genes were mostly carried by one of two isoforms of transposon Tn4401 (Tn4401a or Tn4401b) that were predominantly located on plasmids highly similar to the previously described plasmid pKPC_FCF3SP (IncN). The identified pKPC_FCF3SP-like plasmids carried either blaKPC-2 or blaKPC-30. Two K. pneumoniae isolates harbored pKpQIL-like (IncFII) plasmids, only recently identified in Brazil; one of them harbored blaKPC-3 in a Tn4401a transposon. Underlining the risk of horizontal spread of KPC coding genes, this study reports the prevalence of blaKPC-2 and the recent spread of blaKPC-3, and blaKPC-30, in association with different isoforms of Tn4401, together with high synteny of plasmid backbones among isolates studied here and in comparison with previous reports.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prevalence of blaKPC-2, blaKPC-3 and blaKPC-30—Carrying Plasmids in Klebsiella pneumoniae Isolated in a Brazilian Hospital

et al. 2021

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“…Evolving gradually from multidrug-resistant (MDR) to extensively drugresistant (XDR), K. pneumoniae isolates had not exhibited simultaneous drug resistance and hypervirulence for long until recently with the emergence of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) (2). The primary reason for this delayed emergence has been the successive convergence of two distinct traits of drug resistance and virulence through recombination of several plasmids, resulting in MDR-virulent strains (3). While hvKP has been associated with communityacquired infections, increasing reports of healthcare-associated infections are also being reported (4).…”

Section: Introductionmentioning

confidence: 99%

Extensively Drug-Resistant Hypervirulent Klebsiella pneumoniae From a Series of Neonatal Sepsis in a Tertiary Care Hospital, India

et al. 2021

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The recent emergence of multidrug-resistant (MDR) Klebsiella pneumoniae with hypervirulent traits causing severe infections and considerable mortality is a global cause for concern. The challenges posed by these hypermucoviscous strains of K. pneumoniae with regard to their optimal treatment, management, and control policies are yet to be answered. We studied a series of extensively drug-resistant (XDR) and hypervirulent K. pneumoniae ST5235 isolates with resistance to carbapenems and polymyxins causing neonatal sepsis in a tertiary care hospital in India. A total of 9 K. pneumoniae isolates from 9 cases of neonatal sepsis were studied with respect to their clinical relevance, antimicrobial susceptibility profile, presence of extended spectrum β lactamase (ESBL) production, and responsible genes, carbapenemases (classes A, B, and D), and aminoglycoside-resistant genes. Hypervirulence genes encoding hypermucoid nature, iron uptake, and siderophores were detected by multiplex PCR. The plasmid profile was studied by replicon typing. Isolates were typed by multilocus sequence typing (MLST) and enterobacterial repetitive intergenic consensus (ERIC) PCR to study the sequence types (STs) and clonal relation, respectively. The neonates in the studied cases had history of pre-maturity or low birth weight with maternal complications. All the cases were empirically treated with piperacillin–tazobactam and amikacin followed by imipenem/meropenem and vancomycin and polymyxin B as a last resort. However, all the neonates finally succumbed to the condition (100%). The studied isolates were XDR including resistance to polymyxins harboring multiple ESBL genes and carbapenemase genes (blaNDM and blaOXA−48). Hypervirulence genes were present in various combinations with rmpA/A2 genes present in all the isolates. IncFI plasmids were detected in these isolates. All belonged to ST5235. In ERIC PCR, 6 different clusters were seen. The study highlighted the emergence and burden of XDR hypervirulent isolates of K. pneumoniae causing neonatal sepsis in a tertiary care hospital.

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“…Convergent strains of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKp) have undergone frequent genetic transposition through the formation of a fusion/co-integrate or mosaic plasmid (11).…”

Section: Introductionmentioning

confidence: 99%

“…Notably, these mosaic plasmid are typically composed of two different plasmid backbones and generate the potential for AMR and virulence determinants to be encoded within a single plasmid (12). Similar mosaic plasmid with diverse backbones carrying IncFIB-IncHI1B, IncFIBK-IncHI1B, IncFIB-IncR have been reported in China (11,13,14). These emerging HvKp are extremely preprint (which was not certified by peer review) is the author/funder.…”

Section: Introductionmentioning

confidence: 99%

Mosaic antimicrobial resistance/virulence plasmid in hypervirulent ST2096Klebsiella pneumoniaein India: The rise of a new superbug?

Shankar

Vasudevan

et al. 2020

Preprint

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Hypervirulent K. pneumoniae (HvKp) is typically associated with ST23 clone; however, hvKp is also emerging from clones ST11, ST15 and ST147, which are also multi-drug resistant (MDR). Here, we aimed to characterise nine novel MDR hvKp isolates harbouring mosaic plasmids simultaneously carrying antimicrobial resistance (AMR) and virulence genes. Nine HvKp isolates obtained from hospitalised patients in southern India were characterized for antimicrobial susceptibility and hypervirulence phenotypes. All nine hvKp isolates were subjected to whole genome sequencing (WGS) using Ilumina HiSeq2500 and a subset of four were sequenced using Oxford Nanopore MinION. Among the nine isolates, seven were carbapenem-resistant, two of which carried blaNDM-5 on an IncFII plasmid and five carried blaOXA-232 on a ColKP3 plasmid. The virulence determinants were encoded in a mosaic plasmid (∼320 Kbp) that formed as a result of its insertion in a IncFIB-IncHI1B plasmid co-integrate. The mosaic plasmid carried AMR genes (aadA2, armA, blaOXA-1, msrE, mphE, sul1 and dfrA14) in addition to rmpA2, iutA and iucABCD virulence genes. Interestingly the mosaic plasmid carried its own type IV-A3 CRISPR-cas system that is likely able to target the acquisition of IncF plasmid with the help of a traL spacer. The convergence of virulence and AMR is the biggest threat among invasive K. pneumoniae infections. However, increasing reports of the presence of mosaic plasmid carrying both AMR and virulence genes suggests MDR-hvKp isolates are no longer confined to selected clones and the containment of such isolates is very challenging.IMPORTANCEKlebsiella pneumoniae is an opportunistic pathogen that commonly associated with hospital-acquired infections in the urinary tract, respiratory tract, lung, wound sites. The organism has gained notoriety by acquiring additional genetic traits to become either hypervirulent (HV) phenotype or multidrug resistant (MDR) phenotype. Though the infections by both these phenotypes were very challenging to treat, the MDR K. pneumonia (MDR-Kp) were remained in the hospital settings while HV K. pneumonia (hvKp) strains were mostly originated from the community settings. In a recent turn of events, the evolution of MDR-Kp and hvKp has converged as both clones found to carry both MDR plasmids and virulence plasmid. These convergent strains are challenging to treat and is associated with higher mortality rate. As the recent hvKp isolates harbour mosaic plasmid encoding both AMR and virulence determinants there is a need to investigate the evolution of these pathogens. The significance of our research is in characterising the novel mosaic plasmid identified in MDR-hvKp isolates that belong sequence type (ST) 2096. Tracking the possible evolution pathway of MDR-hvKPs would greatly help in the proper surveillance and management of this superbugs.RepositoriesThe whole genome sequences of the present study isolates have been deposited in GenBank, NCBI, with accession numbers CP053765 - CP053770, CP053771 – CP053780, CP058798-CP058806, JAARNO010000001.1 - JAARNO010000005.1, JAAQSG000000000, JAARNJ000000000, JAARMH000000000 and JAAQTC000000000

show abstract

Carbapenem Resistance-Encoding and Virulence-Encoding Conjugative Plasmids in Klebsiella pneumoniae

Cited by 164 publications

References 85 publications

Prevalence of blaKPC-2, blaKPC-3 and blaKPC-30—Carrying Plasmids in Klebsiella pneumoniae Isolated in a Brazilian Hospital

Prevalence of blaKPC-2, blaKPC-3 and blaKPC-30—Carrying Plasmids in Klebsiella pneumoniae Isolated in a Brazilian Hospital

Extensively Drug-Resistant Hypervirulent Klebsiella pneumoniae From a Series of Neonatal Sepsis in a Tertiary Care Hospital, India

Mosaic antimicrobial resistance/virulence plasmid in hypervirulent ST2096Klebsiella pneumoniaein India: The rise of a new superbug?

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