Klebsiella pneumoniae ST258 Producing KPC-3 Identified in Italy Carries Novel Plasmids and OmpK36/OmpK35 Porin Variants

García-Fernández, Aurora; Villa, Laura; Carta, Claudio; Venditti, Carolina; Giordano, Alessandra; Venditti, Mario; Mancini, Carlo; Carattoli, Alessandra

doi:10.1128/aac.05308-11

Cited by 158 publications

(149 citation statements)

References 23 publications

(23 reference statements)

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…ETP MICs appear to be bimodally distributed in K. pneumoniae, and this seems to correlate with defects and variations in OmpK36, as previously reported in association with KPC-producing isolates, and with ESBL and AmpC-type ␤-lactamases (8,40,55,56). We found a large diversity of OmpK36 defects in our set of ETP-resistant K. pneumoniae isolates, all of which were reported previously: frameshift mutations (43), IS (57), a premature stop codon (58,59), and a GD duplication in loop 3 (44,45,60). OmpK36 was detected by SDS-PAGE only in those isolates with the GD duplication.…”

Section: Discussionsupporting

confidence: 58%

“…The predominance of the GD duplication, also seen in association with bla KPC (43,46), and presumably excluding some large molecules, like ETP, without restricting smaller essential nutrients, is noteworthy. The complete loss of OmpK36 in K. pneumoniae also decreases ␤-lactam susceptibility but might have a greater impact on bacterial fitness, especially in those strains with defects in the other major porin, OmpK35 (38), which are commonly reported in clinical isolates (67).…”

Section: Discussionmentioning

confidence: 99%

“…S1 in the supplemental material). A Gly134Asp135 (GD) duplication in OmpK36 loop 3, commonly seen in sequence type 258 (ST258) isolates carrying bla KPC (43,46) and predicted to functionally constrict the inner channel of the porin, was present in the other 11 isolates (Table 1; see also Fig. S1 in the supplemental material).…”

Section: Detection Of Genes Encoding ␤-Lactamases and Plasmid Typingmentioning

confidence: 99%

“…Nutrients and other hydrophilic molecules, such as ␤-lactam antibiotics, diffuse through these channels, and changes in these pores are linked to decreases in ␤-lactam susceptibility (7-9, 37-39). Previously described changes include disruption of the porin gene or promoter by insertion sequences (IS), frameshifts, nonsense mutations, and insertions or duplications that increase electronegativity of the inner channel-exposed loop 3 region of OmpK porins (40)(41)(42)(43)(44)(45).…”

Section: Detection Of Genes Encoding ␤-Lactamases and Plasmid Typingmentioning

confidence: 99%

See 3 more Smart Citations

Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae

et al. 2016

View full text Add to dashboard Cite

cThe minimal concentration of antibiotic required to inhibit the growth of different isolates of a given species with no acquired resistance mechanisms has a normal distribution. We have previously shown that the presence or absence of transmissible antibiotic resistance genes has excellent predictive power for phenotype. In this study, we analyzed the distribution of six ␤-lactam antibiotic susceptibility phenotypes associated with commonly acquired resistance genes in Enterobacteriaceae in Sydney, Australia. Escherichia coli (n ‫؍‬ 200) and Klebsiella pneumoniae (n ‫؍‬ 178) clinical isolates, with relevant transmissible resistance genes (bla TEM , n ‫؍‬ 33; plasmid AmpC, n ‫؍‬ 69; extended-spectrum ␤-lactamase [ESBL], n ‫؍‬ 116; and carbapenemase, n ‫؍‬ 100), were characterized. A group of 60 isolates with no phenotypic resistance to any antibiotics tested and carrying none of the important ␤-lactamase genes served as comparators. The MICs for all drug-bacterium combinations had a normal distribution, varying only in the presence of additional genes relevant to the phenotype or, for ertapenem resistance in K. pneumoniae, with a loss or change in the outer membrane porin protein OmpK36. We demonstrated mutations in ompK36 or absence of OmpK36 in all isolates in which reduced susceptibility to ertapenem (MIC, >1 mg/liter) was evident. Ertapenem nonsusceptibility in K. pneumoniae was most common in the context of an OmpK36 variant with an ESBL or AmpC gene. Surveillance strategies to define appropriate antimicrobial therapies should include genotype-phenotype relationships for all major transmissible resistance genes and the characterization of mutations in relevant porins in organisms, like K. pneumoniae. E scherichia coli and Klebsiella pneumoniae are among the most important pathogens in community and hospital settings, and their increasing resistance to extended-spectrum (third-and fourth-generation) cephalosporin and carbapenem antibiotics is a major health threat. In Gram-negative bacteria, such as these, a variety of mechanisms may confer ␤-lactam resistance (1), but the spread of transmissible genes encoding extended-spectrum ␤-lactamases (ESBLs) (2), plasmid-mediated AmpC ␤-lactamases (pAmpCs) (3), and carbapenemases (4) is particularly significant. Carbapenems have been the antibiotics of choice for treating ESBLs and other multidrug-resistant strains, but carbapenem resistance is increasingly common (5). This is mostly attributed to the production of specific carbapenemases (6), but the expression of AmpC or ESBL enzymes in isolates with altered outer membrane porins is also associated with decreased susceptibility to carbapenems (7-9). Mutations in major outer membrane porins may be required for clinically relevant carbapenem resistance in K. pneumoniae isolates expressing carbapenemases, such as KPC and OXA-48-like enzymes, which rarely elicit clinically important antibiotic resistance in E. coli (6).The clinical definitions of antibiotic susceptibility are developed by the collection and analysis of...

show abstract

Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Detection Of Genes Encoding ␤-Lactamases and Plasmid Typingmentioning

confidence: 99%

Section: Detection Of Genes Encoding ␤-Lactamases and Plasmid Typingmentioning

confidence: 99%

See 2 more Smart Citations

Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Horizontal Gene Transfer (HGT) -between bacteria [4,14,15]. Furthermore, the capacity of the K. pneumoniae to colonize medical equipment and to survive for long periods of time, at extreme temperature in the environment, explains why this pathogen can also be isolated from hospital environment and play an important role in the horizontal transfer of antibiotic resistance, acting also as an efficient donor and receptor [4,13,[16][17][18][19]. The events observed in the present study, suggest that asymptomatic carriers, such as health professionals and their flow between different hospitals; patient or other people who move through hospitals, may be contributing to the local dissemination of these clones, which may affect vulnerable patients [13].…”

Section: Textmentioning

confidence: 99%

Molecular Epidemiology of KPC-2 Producing Klebsiella pneumoniae

Ferreira¹

2017

SOJMID

View full text Add to dashboard Cite

We describe the molecular epidemiology of the KPC-2 K. pneumoniae among public hospitals in the Amazon State, Brazil. A total of 4.4% (5/113) of the K. pneumoniae isolates were identified as KPC-producing and CTX-M-109 beta-lactamase. Further, MultiLocus Sequence Typing identified three clones STs11, 40 and 2230. To the best of our knowledge, the present study demonstrates for the very first time, detection of the multidrug resistant K. pneumoniae (KPC-2), ST2230 clone, in Brazil.

show abstract

Molecular Characterization of an Atypical IncX3 Plasmid pKPC-NY79 Carrying bla KPC-2 in a Klebsiella pneumoniae

Cheung

et al. 2013

Curr Microbiol

View full text Add to dashboard Cite

The IncX family of plasmids has recently been expanded to include at least four subtypes, IncX1-IncX4. The revised classification provides an opportunity for improving our understanding of the sequence diversity of the IncX plasmids and the resistance genes they carried. We described the complete nucleotide sequence of a novel IncX3 plasmid, pKPC-NY79 (42,447 bp) from a sequence-type 258 Klebsiella pneumoniae strain that was isolated from a patient who was hospitalized in New York, United States. In pKPC-NY79, the plasmid scaffold and genetic load region were highly similar to homologous regions in pIncX-SHV (IncX3, JN247852) and the bla KPC carrying pKpQIL (IncFIIk, GU595196), respectively, indicating that it has possibly arisen through recombination of plasmids. The bla KPC-2 gene, as part of a transposon Tn4401a, was found within the genetic load region. The backbone of pKPC-NY79 differs from pIncX-SHV by a deletion involving the gene tandem hns-topB (encoding H-NS protein and topoisomerase III, respectively) and a putative ATPase gene. Unexpectedly, the impact of the hns-topB deletion on host fitness and plasmid stability was found to be small. In conclusion, the findings contribute to a better understanding of the plasmid platforms carrying bla KPC and of variations in the backbone of the IncX3 plasmids.

show abstract

Klebsiella pneumoniae ST258 Producing KPC-3 Identified in Italy Carries Novel Plasmids and OmpK36/OmpK35 Porin Variants

Cited by 158 publications

References 23 publications

Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae

Predictability of Phenotype in Relation to Common β-Lactam Resistance Mechanisms in Escherichia coli and Klebsiella pneumoniae

Molecular Epidemiology of KPC-2 Producing Klebsiella pneumoniae

Molecular Characterization of an Atypical IncX3 Plasmid pKPC-NY79 Carrying bla KPC-2 in a Klebsiella pneumoniae

Contact Info

Product

Resources

About