Reversion to susceptibility of a carbapenem-resistant clinical isolate of Klebsiella pneumoniae producing KPC-3

Villa, Laura; Capone, Alessandro; Fortini, Daniela; Dolejská, Monika; Rodríguez, Irene; Taglietti, Fabrizio; Paolis, Paolo De; Petrosillo, Nicola; Carattoli, Alessandra

doi:10.1093/jac/dkt235

Cited by 44 publications

(31 citation statements)

References 17 publications

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“…It is plausible that the D179Y variant has reduced hydrolytic activity against carbapenems (12), a hypothesis we will test in future enzyme kinetics studies. This mechanism of restored carbapenem susceptibility would differ from that previously reported for a KPC-3-producing K. pneumoniae isolate in which plasmid rearrangements resulted in deletion of the Tn4401::bla KPC-3 transposon (16).…”

contrasting

confidence: 87%

In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases

Shields

Nguyen

Press

et al. 2017

Antimicrob Agents Chemother

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Ceftazidime-avibactam resistance is mediated by bla KPC-3 mutations, which restore carbapenem susceptibility. We subjected Klebsiella pneumoniae isolates with different bla KPC-3 mutations (n ϭ 5) or wild-type bla KPC-3 (n ϭ 2) to serial passages with meropenem. The meropenem MIC against each isolate increased. Mutations in the ompK36 porin gene evolved in 5 isolates. Among isolates with D179Y substitutions in KPC-3, bla KPC-3 mutations reverted to wild type, were replaced by new mutations, or were retained. Carbapenem treatment of ceftazidime-avibactam-resistant K. pneumoniae infections may select for carbapenem resistance.

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contrasting

confidence: 87%

In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases

Shields

Nguyen

Press

et al. 2017

Antimicrob Agents Chemother

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“…Members of the pKpQIL plasmid family have been responsible globally for a number of CRE outbreaks (3,5,7,31,(33)(34)(35)(36). In pKpQIL and related plasmids, the bla KPC gene is located within a Tn4401 transposon sequence (4,37,38).…”

Section: Discussionmentioning

confidence: 99%

A Rapid Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry-Based Method for Single-Plasmid Tracking in an Outbreak of Carbapenem-Resistant Enterobacteriaceae

et al. 2014

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e Carbapenem-resistant Enterobacteriaceae (CRE) have spread globally and represent a serious and growing threat to public health. Rapid methods for tracking plasmids carrying carbapenemase genes could greatly benefit infection control efforts. Here, we demonstrate that real-time, direct tracking of a single plasmid in a bacterial strain responsible for an outbreak is possible using a commercial matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. In this case, we retrospectively tracked the bla KPC carbapenemase gene-bearing pKpQIL plasmid responsible for a CRE outbreak that occurred at the NIH Clinical Center in 2011. An ϳ11,109-Da MS peak corresponding to a gene product of the bla KPC pKpQIL plasmid was identified and characterized using a combination of proteomics and molecular techniques. This plasmid peak was present in spectra from retrospectively analyzed K. pneumoniae outbreak isolates, concordant with results from whole-genome sequencing, and absent from a diverse control set of bla KPC -negative clinical Enterobacteriaceae isolates. Notably, the gene characterized here is located adjacent to the bla KPC Tn4401 transposon on the pKpQIL plasmid. Sequence analysis demonstrates the presence of this gene in other bla KPC Tn4401-containing plasmids and suggests that this signature MS peak may be useful in tracking other plasmids conferring carbapenem resistance. Plasmid identification using this MALDI-TOF MS method was accomplished in as little as 10 min from isolated colonies and 30 min from positive (spiked) blood cultures, demonstrating the potential clinical utility for real-time plasmid tracking in an outbreak.

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“…A set of 24 complete sequences of plasmids associated with important resistance determinants, covering 12 different replicon groups as determined in previous studies by PBRT (5,8,9,(17)(18)(19)(20)(21)(22)(23)(24), were used to test the ability of PlasmidFinder to detect the correct plasmid replicons. Here, the replicon sequences from the PlasmidFinder database were BLASTed against the complete plasmid sequences and the best-matching hits in each genome for each replicon sequence were given as output using a % ID threshold value of 80%.…”

Section: Methodsmentioning

confidence: 99%

In Silico Detection and Typing of Plasmids using PlasmidFinder and Plasmid Multilocus Sequence Typing

Carattoli

Zankari

García-Fernández

et al. 2014

Antimicrob Agents Chemother

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2,829

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cIn the work presented here, we designed and developed two easy-to-use Web tools for in silico detection and characterization of whole-genome sequence (WGS) and whole-plasmid sequence data from members of the family Enterobacteriaceae. These tools will facilitate bacterial typing based on draft genomes of multidrug-resistant Enterobacteriaceae species by the rapid detection of known plasmid types. Replicon sequences from 559 fully sequenced plasmids associated with the family Enterobacteriaceae in the NCBI nucleotide database were collected to build a consensus database for integration into a Web tool called PlasmidFinder that can be used for replicon sequence analysis of raw, contig group, or completely assembled and closed plasmid sequencing data. The PlasmidFinder database currently consists of 116 replicon sequences that match with at least at 80% nucleotide identity all replicon sequences identified in the 559 fully sequenced plasmids. For plasmid multilocus sequence typing (pMLST) analysis, a database that is updated weekly was generated from www .pubmlst.org and integrated into a Web tool called pMLST. Both databases were evaluated using draft genomes from a collection of Salmonella enterica serovar Typhimurium isolates. PlasmidFinder identified a total of 103 replicons and between zero and five different plasmid replicons within each of 49 S. Typhimurium draft genomes tested. The pMLST Web tool was able to subtype genomic sequencing data of plasmids, revealing both known plasmid sequence types (STs) and new alleles and ST variants. In conclusion, testing of the two Web tools using both fully assembled plasmid sequences and WGS-generated draft genomes showed them to be able to detect a broad variety of plasmids that are often associated with antimicrobial resistance in clinically relevant bacterial pathogens. P lasmids are double-stranded circular or linear DNA molecules capable of autonomous replication and transferable between different bacterial species and clones. Most of the known plasmids have been identified because they confer phenotypes that are subject to positive selection on the bacterial host, such as the presence of antimicrobial resistance or virulence genes. Such features aid the successful spread of different plasmid types among bacteria of different sources and geographical origins. The acquisition of plasmids carrying antimicrobial resistance or virulence genes might drastically alter the prevalence of virulent or multidrug resistant-bacterial clones. It is thus important not only to study the molecular epidemiology of different bacterial clones but also to study and understand the molecular epidemiology of transferable plasmids. For this specific purpose, plasmid typing systems are needed.Most plasmids include specific regions, called replicons, encoding functions that are able to activate and control replication (1). Since 2005, a PCR-based replicon typing (PBRT) scheme has been available that targets in multiplex PCRs the replicons of the major plasmid families occurring in members o...

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Reversion to susceptibility of a carbapenem-resistant clinical isolate of Klebsiella pneumoniae producing KPC-3

Abstract: The description of the plasmid content in these two strains gives interesting insights into the plasticity of KPC-carrying plasmids in K. pneumoniae.

Cited by 44 publications

References 17 publications

In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases

In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases

A Rapid Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry-Based Method for Single-Plasmid Tracking in an Outbreak of Carbapenem-Resistant Enterobacteriaceae

In Silico Detection and Typing of Plasmids using PlasmidFinder and Plasmid Multilocus Sequence Typing

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