scholarly journals Genetic Factors Associated with Elevated Carbapenem Resistance in KPC-Producing Klebsiella pneumoniae

2010 ◽  
Vol 54 (10) ◽  
pp. 4201-4207 ◽  
Author(s):  
Brandon Kitchel ◽  
J. Kamile Rasheed ◽  
Andrea Endimiani ◽  
Andrea M. Hujer ◽  
Karen F. Anderson ◽  
...  
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
Copy Number ◽  
Gene Copy Number ◽  
Carbapenem Resistance ◽  
The United States ◽  
Gene Copy ◽  
Sequencing Analysis ◽  
Low Level ◽  
High Level

ABSTRACT In the United States, the most prevalent mechanism of carbapenem resistance among Enterobacteriaceae is the production of a Klebsiella pneumoniae carbapenemase (KPC). KPC-producing isolates often exhibit a range of carbapenem MICs. To better understand the factors that contribute to overall carbapenem resistance, we analyzed 27 KPC-producing K. pneumoniae isolates with different levels of carbapenem resistance, 11 with low-level (i.e., meropenem or imipenem MIC ≤ 4 μg/ml), 2 with intermediate-level (i.e., meropenem and imipenem MIC = 8 μg/ml), and 14 with high-level (i.e., imipenem or meropenem MIC ≥ 16 μg/ml) carbapenem resistance, that were received from throughout the United States. Among 14 isolates that exhibited high-level carbapenem resistance, Western blot analysis indicated that 10 produced an elevated amount of KPC. These isolates either contained an increased bla KPC gene copy number (n = 3) or had deletions directly upstream of the bla KPC gene (n = 7). Four additional isolates lacked elevated KPC production but had high-level carbapenem resistance. Porin sequencing analysis identified 22 isolates potentially lacking a functional OmpK35 and three isolates potentially lacking a functional OmpK36. The highest carbapenem MICs were found in two isolates that lacked both functioning porins and produced elevated amounts of KPC. The 11 isolates with low-level carbapenem resistance contained neither an upstream deletion nor increased bla KPC copy number. These results suggest that both bla KPC copy number and deletions in the upstream genetic environment affect the level of KPC production and may contribute to high-level carbapenem resistance in KPC-producing K. pneumoniae, particularly when coupled with OmpK36 porin loss.

scholarly journals Nosocomial Outbreak of Carbapenemase-Producing Proteus mirabilis With Two Novel Salmonella Genomic Island 1 Variants Carrying Different blaNDM–1 Gene Copies in China

2022 ◽  
Vol 12 ◽  
Author(s):  
Lang Yang ◽  
Hong He ◽  
Qichao Chen ◽  
Kaiying Wang ◽  
Yanfeng Lin ◽  
...  
Keyword(s):  
Proteus Mirabilis ◽  
Copy Number ◽  
Genomic Island ◽  
Gene Copy Number ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Gene Copy ◽  
Nosocomial Outbreak ◽  
Gene Copy Number Variation ◽  
Gene Copies

NDM-1-producing multidrug-resistant Proteus mirabilis brings formidable clinical challenges. We report a nosocomial outbreak of carbapenem-resistant P. mirabilis in China. Six P. mirabilis strains collected in the same ward showed close phylogenetic relatedness, indicating clonal expansion. Illumina and MinION sequencing revealed that three isolates harbored a novel Salmonella genomic island 1 carrying a blaNDM–1 gene (SGI1-1NDM), while three other isolates showed elevated carbapenem resistance and carried a similar SGI1 but with two blaNDM–1 gene copies (SGI1-2NDM). Four new single nucleotide mutations were present in the genomes of the two-blaNDM–1-harboring isolates, indicating later emergence of the SGI1-2NDM structure. Passage experiments indicated that both SGI variants were stably persistent in this clone without blaNDM–1 copy number changes. This study characterizes two novel blaNDM–1-harboring SGI1 variants in P. mirabilis and provides a new insight into resistance gene copy number variation in bacteria.

scholarly journals Multicity Outbreak of Carbapenem-Resistant Acinetobacter baumannii Isolates Producing the Carbapenemase OXA-40

2006 ◽  
Vol 50 (9) ◽  
pp. 2941-2945 ◽  
Author(s):  
Karen Lolans ◽  
Thomas W. Rice ◽  
L. Silvia Munoz-Price ◽  
John P. Quinn
Keyword(s):  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
The United States ◽  
Nucleotide Sequencing ◽  
Sequencing Analysis ◽  
Carbapenem Resistant ◽  
Extended Care ◽  
Care Facilities ◽  
High Level ◽  
First Time

ABSTRACT During 2005 we detected a multicity outbreak of infections or colonization due to high-level imipenem-resistant Acinetobacter baumannii (MIC, 64 μg/ml). One hundred isolates from diverse sources were obtained from seven acute-care hospitals and two extended-care facilities; 97% of the isolates belonged to one clone. Susceptibility testing of the first 42 isolates (January to April 2005) revealed broad resistance profiles. Half of the isolates were susceptible to ceftazidime, with many isolates susceptible only to colistin. The level of AmpC β-lactamase expression was stronger in isolates resistant to ceftazidime. PCR and subsequent nucleotide sequencing analysis identified bla OXA-40. The presence of an OXA-40 β-lactamase in these isolates correlated with the carbapenem resistance. By Southern blot analysis, a bla OXA-40-specific probe revealed that the gene was both plasmid and chromosomally located. This is the first time in the United States that such carbapenem resistance in A. baumannii has been attributable to a carbapenemase.

Evolutionary Trajectories toward Ceftazidime-Avibactam Resistance in Klebsiella pneumoniae Clinical Isolates

2021 ◽  
Author(s):  
Alessandra Carattoli ◽  
Gabriele Arcari ◽  
Giulia Bibbolino ◽  
Federica Sacco ◽  
Dario Tomolillo ◽  
...  
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Copy Number ◽  
Residual Activity ◽  
Gene Copy Number ◽  
Resistance Mechanisms ◽  
University Hospital ◽  
Gene Copy ◽  
Carbapenemase Gene ◽  
Evolutionary Trajectories

From January 2019 to April 2020, 32 KPC-producing, ceftazidime-avibactam (CZA) resistant Klebsiella pneumoniae strains were isolated in a university hospital in Rome, Italy. These strains belonged to the ST512, ST101 and ST307 high-risk clones. Nine different CZA-resistant KPC-3 protein variants were identified, five of them never previously reported (KPC-66 to KPC-70). Among them, KPC-31, KPC-39, KPC-49, KPC-66, KP-68, KPC-69 and KPC-70 showed amino acid substitutions, insertions and deletions in the Ω loop of the protein. KPC-29 has the duplication, while the novel KPC-67 has the triplication of the KDD triplet in the 270-loop of the protein. Genomics performed on contemporary resistant and susceptible clones underlined that those novel mutations emerged in bla KPC-3 genes located on conserved plasmids: in ST512, all bla KPC-3 mutant genes were located in pKpQIL plasmids, while the three novel bla KPC-3 mutants identified in ST101 were on FIIk-FIA(HI1)-R plasmids. Selection also promoted multiplication of the carbapenemase gene copy number by transposition, recombination, and fusion of resident plasmids. When expressed in Escherichia coli recipient cells cloned in the high-copy number pTOPO vector, the Ω loop mutated variants showed CZA-resistant phenotype associated with susceptibility to carbapenems, while KPC variants with insertions in the 270-loop showed residual activity on carbapenems. The investigation of CZA-resistance mechanisms offered the unique opportunity to study vertical, horizontal, and oblique evolutionary trajectories of K. pneumoniae high-risk clones.

scholarly journals Ceftazidime-Avibactam Resistance Associated with Increased blaKPC-3 Gene Copy Number Mediated by pKpQIL Plasmid Derivatives in Sequence Type 258 Klebsiella pneumoniae

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Marco Coppi ◽  
Vincenzo Di Pilato ◽  
Francesco Monaco ◽  
Tommaso Giani ◽  
Pier Giulio Conaldi ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Copy Number ◽  
Acquired Resistance ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Content Type ◽  
Outer Membrane Porins ◽  
Long Read ◽  
Multiple Copies

ABSTRACT This study reports on the characterization of two ceftazidime-avibactam (CZA)-resistant KPC-producing Klebsiella pneumoniae strains (KP-14159 and KP-8788) sequentially isolated from infections occurred in a patient never treated with CZA. Whole-genome sequencing characterization using a combined short- and long-read sequencing approach showed that both isolates belonged to the same ST258 strain, had altered outer membrane porins (a truncated OmpK35 and an Asp137Thr138 duplication in the L3 loop of OmpK36), and carried novel pKpQIL plasmid derivatives (pIT-14159 and pIT-8788, respectively) harboring two copies of the Tn4401a KPC-3-encoding transposon. Plasmid pIT-8788 was a cointegrate of pIT-14159 with a ColE replicon (that was also present in KP-14159) apparently evolved in vivo during infection. pIT-8788 was maintained at a higher copy number than pIT-14159 and, upon transfer to Escherichia coli DH10B, was able to increase the CZA MIC by 32-fold. The present findings provide novel insights about the mechanisms of acquired resistance to CZA, underscoring the role that the evolution of broadly disseminated pKpQIL plasmid derivatives may have in increasing the blaKPC gene copy number and KPC-3 expression in bacterial hosts. Although not self-transferable, similar elements, with multiple copies of Tn4401 and maintained at a high copy number, could mediate transferable CZA resistance upon mobilization.

scholarly journals Has Robert Parker lost his hegemony as a prescriptor in the wine World? A preliminar inquiry through Twitter

2018 ◽  
Author(s):  
Cristina I. Font-Julian ◽  
Raúl Compés-López ◽  
Enrique Orduna-Malea
Keyword(s):  
United States ◽  
Comparative Analysis ◽  
Social Activity ◽  
The United States ◽  
Prima Facie ◽  
Low Level ◽  
The World ◽  
English Speaking ◽  
Online Strategy ◽  
High Level

The aim of this work is to determine to what extent Robert Parker has lost his influence as a prescriber in the world of wine through a webometric analysis based on a comparative analysis of Parker’s web influence and that of a competitor who represents an anthitetical vision of the world of wine (Alice Feiring). To do this, we carried out a comparative analysis for Parker’s (@wine_advocate) and Alice Feiring’s (@alicefeiring) official Twitter accounts, including a broad set of metrics (productivity, age, Social Activity, number of followees, etc.), paying special attention to specific followers’ features (age, gender, location, and bios text). The results show that Parker’s twitter profile exhibits an overall higher impact, which denotes not only a different online strategy but also a high level of engagement and popularity. The low level of shared followers by Parker and Feiring (1,898 users) offer prima facie evidence of an online gap between these followers, which can indicate the existence of a divided group of supporters corresponding with the visions that Parker and Feiring represent. Finally, special features are notice for Feiring in gender (more women followers), language (more English-speaking followers) and country (more followers from the United States).

scholarly journals blaKPCRNA Expression Correlates with Two Transcriptional Start Sites but Not Always with Gene Copy Number in Four Genera of Gram-Negative Pathogens

2011 ◽  
Vol 55 (8) ◽  
pp. 3936-3938 ◽  
Author(s):  
Amanda L. Roth ◽  
Philip M. Kurpiel ◽  
Philip D. Lister ◽  
Nancy D. Hanson
Keyword(s):  
Gene Expression ◽  
Klebsiella Pneumoniae ◽  
Copy Number ◽  
Susceptibility Testing ◽  
Gene Copy Number ◽  
Clinical Isolates ◽  
Gene Copy ◽  
Gram Negative ◽  
Transcriptional Start Sites

ABSTRACTKlebsiella pneumoniaecarbapenemase (KPC)-producing organisms are therapeutically and diagnostically challenging. It is possible thatblaKPCgene expression plays a role in the variability observed in clinical susceptibility testing.blaKPCtransformants together with 10 clinical isolates representing four genera were evaluated forblaKPCcopy number and gene expression and correlated with β-lactam MIC data. The data suggest that mechanisms other than gene copy number and expression ofblaKPCcontribute to variability in susceptibility when testing KPC-producing isolates.

scholarly journals Broader Distribution of Plasmid-Mediated Quinolone Resistance in the United States

2005 ◽  
Vol 49 (7) ◽  
pp. 3001-3003 ◽  
Author(s):  
A. Robicsek ◽  
D. F. Sahm ◽  
J. Strahilevitz ◽  
G. A. Jacoby ◽  
D. C. Hooper
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
Resistance Gene ◽  
The United States ◽  
Quinolone Resistance ◽  
Low Level ◽  
Level Resistance ◽  
Selection Of

ABSTRACT The plasmid-encoded quinolone resistance gene qnrA confers low-level quinolone resistance, facilitating selection of higher-level resistance. Epidemiologic surveys for qnrA were extended to isolates of Enterobacter spp. and to quinolone-susceptible Enterobacteriaceae. Two (10%) of 20 ceftazidime-resistant quinolone-susceptible Klebsiella pneumoniae strains carried the gene, as did 12 (17%) of 71 ceftazidime-resistant Enterobacter strains from across the United States. One of these Enterobacter isolates was quinolone susceptible. Thus, qnrA is present in quinolone-resistant and quinolone-susceptible Enterobacter and Klebsiella strains in the United States.

scholarly journals Regional Dissemination of KPC-Producing Klebsiella pneumoniae

2009 ◽  
Vol 53 (10) ◽  
pp. 4511-4513 ◽  
Author(s):  
Brandon Kitchel ◽  
Daniel R. Sundin ◽  
Jean B. Patel
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
Molecular Typing ◽  
Carbapenem Resistance ◽  
The United States ◽  
Sequence Type ◽  
Common Mechanism

ABSTRACT Production of a Klebsiella pneumoniae carbapenemase (KPC) is the most common mechanism of carbapenem resistance in the United States; however, until now, KPC-producing isolates have not been found in western Michigan. Molecular typing of two KPC-producing K. pneumoniae isolates from Michigan showed their similarity to other Midwestern isolates. They were also unrelated to the dominant sequence type observed throughout the United States, multilocus sequence type 258. This could represent regional dissemination of another KPC-producing K. pneumoniae strain.

scholarly journals The influence of antibiotics on transitory resistome during gut colonization with CTX-M-15 and OXA-162 producing Klebsiella pneumoniae ST15

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Balázs Stercz ◽  
Ferenc B. Farkas ◽  
Ákos Tóth ◽  
Márió Gajdács ◽  
Judit Domokos ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Resistance Gene ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Antibiotic Administration ◽  
Mice Model ◽  
Gut Colonization ◽  
Colonization Rates

AbstractGreat efforts have been made to limit the transmission of carbapenemase-producing Enterobacteriaceae (CPE), however, the intestinal reservoir of these strains and its modulation by various antibiotics remain largely unexplored. Our aim was to assess the effects of antibiotic administration (ampicillin, ceftazidime, ciprofloxacin) on the establishment and elimination of intestinal colonization with a CTX-M-15 ESBL and OXA-162 carbapenemase producing Klebsiella pneumoniae ST15 (KP5825) in a murine (C57BL/6 male mice) model. Whole genome sequencing of KP5825 strain was performed on an Illumina MiSeq platform. Conjugation assays were carried out by broth mating method. In colonization experiments, 5 × 106 CFU of KP5825 was administered to the animals by orogastric gavage, and antibiotics were administered in their drinking water for two weeks and were changed every day. The gut colonization rates with KP5825 were assessed by cultivation and qPCR. In each of the stool samples, the gene copy number of blaOXA-162 and blaCTX-M-15 were determined by qPCR. Antibiotic concentrations in the stool were determined by high pressure liquid chromatography and a bioanalytical method. The KP5825 contained four different plasmid replicon types, namely IncFII(K), IncL, IncFIB and ColpVC. IncL (containing the blaOXA-162 resistance gene within a Tn1991.2 genetic element) and IncFII(K) (containing the blaCTX-M-15 resistance gene) plasmids were successfully conjugated. During ampicillin and ceftazidime treatments, colonization rate of KP5825 increased, while, ciprofloxacin treatments in both concentrations (0.1 g/L and 0.5 g/L) led to significantly decreased colonization rates. The gene copy number blaOXA-162 correlated with K. pneumoniae in vivo, while a major elevation was observed in the copy number of blaCTX-M-15 from the first day to the fifteenth day in the 0.5 g/L dose ceftazidime treatment group. Our results demonstrate that commonly used antibiotics may have diverse impacts on the colonization rates of intestinally-carried CPE, in addition to affecting the gene copy number of their resistance genes, thus facilitating their stable persistance and dissemination.

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