scholarly journals Sequence Type 273 Carbapenem-Resistant Klebsiella pneumoniae Carrying bla NDM-1 and bla IMP-4

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Lu Liu ◽  
Yu Feng ◽  
Haiyan Long ◽  
Alan McNally ◽  
Zhiyong Zong
Keyword(s):  
Klebsiella Pneumoniae ◽  
Southeast Asia ◽  
Human Blood ◽  
Sequence Type ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Transmissible Plasmid ◽  
Long Read

ABSTRACT A carbapenem-resistant Klebsiella pneumoniae isolate was recovered from human blood. Its whole-genome sequence was obtained using Illumina and long-read MinION sequencing. The strain belongs to sequence type 273 (ST273), which was found recently and caused an outbreak in Southeast Asia. It has two carbapenemase genes, bla NDM-1 (carried by an ST7 IncN self-transmissible plasmid) and bla IMP-4 (located on a self-transmissible IncHI5 plasmid). Non-KPC-producing ST237 may represent a lineage of carbapenem-resistant K. pneumoniae , which warrants further monitoring.

scholarly journals Whole-Genome Sequence of a Novel Sequence Type 3136 Carbapenem-Resistant Klebsiella pneumoniae Strain Isolated from a Hospitalized Patient in Durban, South Africa

2018 ◽  
Vol 7 (23) ◽  
Author(s):  
Yogandree Ramsamy ◽  
Koleka P. Mlisana ◽  
Mushal Allam ◽  
Arshad Ismail ◽  
Ravesh Singh ◽  
...  
Keyword(s):  
South Africa ◽  
Klebsiella Pneumoniae ◽  
Virulence Factors ◽  
Genome Sequence ◽  
Sequence Type ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Resistance Determinants ◽  
Carbapenem Resistant

Here, we describe the genome sequence of a novel sequence type 3136 (ST3136) Klebsiella pneumoniae strain isolated in South Africa. The 5,574,236-bp genome harbored 23 resistance determinants and 12 virulence factors that are of cardinal importance to infections.

scholarly journals Spread of Carbapenem-Resistant Klebsiella pneumoniae in an Intensive Care Unit: A Whole-Genome Sequence-Based Prospective Observational Study

2021 ◽  
Author(s):  
Li Wei ◽  
Linfei Wu ◽  
Hongxia Wen ◽  
Yu Feng ◽  
Shichao Zhu ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Klebsiella Pneumoniae ◽  
Prospective Observational Study ◽  
Opportunistic Pathogen ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Human Infections

Klebsiella pneumoniae can be an opportunistic pathogen with the oral cavity and gut the main origin. However, carbapenem-resistant Klebsiella pneumoniae (CRKP) can be found in patient surroundings and is a serious threat for human infections.

scholarly journals Survival of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 258 in Human Blood

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Frank R. DeLeo ◽  
Scott D. Kobayashi ◽  
Adeline R. Porter ◽  
Brett Freedman ◽  
David W. Dorward ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Human Serum ◽  
Host Defense ◽  
Human Blood ◽  
Bactericidal Activity ◽  
Sequence Type ◽  
Serum Complement ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Normal Human

ABSTRACT Klebsiella pneumoniae is a prominent cause of nosocomial infections worldwide. Bloodstream infections caused by carbapenem-resistant K. pneumoniae, including the epidemic lineage known as multilocus sequence type 258 (ST258), are difficult to treat, and the rate of mortality from such infections is high. Thus, it is imperative that we gain a better understanding of host defense against this pathogen as a step toward developing novel therapies. Here we tested the hypothesis that the resistance of ST258 to bactericidal components of human blood, such as serum complement, is linked to virulence capacity in the context of bacteremia. There was significant variance in the survival of ST258 clinical isolates in heparinized human blood or normal human serum. The rate of survival of ST258 isolates in human blood was, in general, similar to that in normal human serum, suggesting a prominent role for complement (rather than leukocytes) in the healthy host defense against ST258 isolates and related organisms. Indeed, deposition of serum complement—the C5b to C9 (C5b-C9) membrane attack complex—onto the surface of ST258 isolates accompanied serum bactericidal activity. Human serum treated with pharmacological inhibitors of complement, depleted of antibody, or heated at 56°C for 30 min had significantly reduced or absent bactericidal activity. In contrast to heparinized blood from humans, that from BALB/c mice lacked bactericidal activity toward the ST258 isolates tested, but the virulence of these ST258 isolates in a mouse bacteremia model was inexplicably limited. Our data highlight the importance of the complement system in host defense against ST258 bacteremia, and we propose that there is the potential to enhance complement-mediated bactericidal activity using an antibody-based approach.

scholarly journals Successive Emergence of Ceftazidime-Avibactam Resistance through Distinct Genomic Adaptations in bla KPC-2 -Harboring Klebsiella pneumoniae Sequence Type 307 Isolates

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Marla J. Giddins ◽  
Nenad Macesic ◽  
Medini K. Annavajhala ◽  
Stephania Stump ◽  
Sabrina Khan ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Rapid Evolution ◽  
Carbapenem Resistance ◽  
Sequence Type ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Oxford Nanopore ◽  
Long Read ◽  
Stepwise Evolution ◽  
Emergence Of Resistance

ABSTRACT Ceftazidime-avibactam (CAZ-AVI) is a promising novel treatment for infections caused by carbapenem-resistant Enterobacteriaceae (CRE). Despite improved treatment outcomes compared to those achieved with aminoglycoside- and colistin-based regimens, the rapid evolution of CAZ-AVI resistance during treatment has previously been reported in Klebsiella pneumoniae sequence type 258 (ST258) bla KPC-3 -harboring isolates. Here, we report the stepwise evolution and isolation of two phenotypically distinct CAZ-AVI-resistant Klebsiella pneumoniae isolates from a patient with pancreatitis. All susceptible ( n = 3) and resistant ( n = 5) isolates were of the ST307 clonal background, a rapidly emerging clone. Taking advantage of short-read Illumina and long-read Oxford Nanopore sequencing and full-length assembly of the core chromosome and plasmids, we demonstrate that CAZ-AVI resistance first occurred through a 532G → T bla KPC-2 point mutation in bla KPC-2 (D179Y protein substitution) following only 12 days of CAZ-AVI exposure. While subsequent isolates exhibited substantially decreased meropenem (MEM) MICs (≤2 μg/ml), later cultures demonstrated a second CAZ-AVI resistance phenotype with a lower CAZ-AVI MIC (12 μg/ml) but also MEM resistance (MIC > 128 μg/ml). These CAZ-AVI- and MEM-resistant isolates showed evidence of multiple genomic adaptations, mainly through insertions and deletions. This included amplification and transposition of wild-type bla KPC-2 into a novel plasmid, an IS 1 insertion upstream of ompK36 , and disruption of the rfb gene locus in these isolates. Our findings illustrate the potential of CAZ-AVI resistance to emerge in non- K. pneumoniae ST258 clonal backgrounds and alternative bla KPC variants. These results raise concerns about the strong selective pressures incurred by novel carbapenemase inhibitors, such as avibactam, on isolates previously considered invulnerable to CAZ-AVI resistance. There is an urgent need to further characterize non-KPC-mediated modes of carbapenem resistance and the intrinsic bacterial factors that facilitate the rapid emergence of resistance during treatment.

scholarly journals First Whole-Genome Sequence of a Highly Resistant Klebsiella pneumoniae Sequence Type 14 Strain Isolated from Sudan

2019 ◽  
Vol 8 (32) ◽  
Author(s):  
Sofia B. Mohamed ◽  
Sumaya Kambal ◽  
Abdalla Munir ◽  
Nusiba Abdalla ◽  
Mohamed Hassan ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genomic Sequence ◽  
Significant Proportion ◽  
Opportunistic Pathogen ◽  
Sequence Type ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Hospital Acquired

Klebsiella pneumoniae is an opportunistic pathogen that accounts for a significant proportion of hospital-acquired infections and is a leading cause of nosocomial outbreaks. Here, we describe the genomic sequence of a highly resistant K. pneumoniae sequence type 14 (ST14) strain isolated from Sudan.

scholarly journals Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by Chromosomal Integration of Plasmid DNA

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Astrid V. Cienfuegos-Gallet ◽  
Liang Chen ◽  
Barry N. Kreiswirth ◽  
J. Natalia Jiménez
Keyword(s):  
Klebsiella Pneumoniae ◽  
Plasmid Dna ◽  
Clonal Expansion ◽  
Genetic Alterations ◽  
Sequence Type ◽  
Chromosomal Integration ◽  
Colistin Resistance ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Single Locus Variant

ABSTRACT Here we describe the spread of colistin resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae in Medellín, Colombia. Among 32 isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB. Nineteen isolates belonged to sequence type 512 (ST512) (or its single locus variant [SLV]) and harbored an 8.1-kb hsdMSR insertion corresponding to ISKpn25, indicating a clonal expansion of the resistant strain. The insertion region showed 100% identity to several plasmids, suggesting that the colistin resistance is mediated by chromosomal integration of plasmid DNA.

scholarly journals Dynamics of blaKPC-2 Dissemination from Non-CG258 Klebsiella pneumoniae to Other Enterobacterales via IncN Plasmids in an Area of High Endemicity

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Ana M. Rada ◽  
Elsa De La Cadena ◽  
Carlos Agudelo ◽  
Cesar Capataz ◽  
Nataly Orozco ◽  
...  
Keyword(s):  
Public Health ◽  
Klebsiella Pneumoniae ◽  
Neonatal Intensive Care ◽  
Carbapenem Resistance ◽  
Health Interventions ◽  
Global Public Health ◽  
Public Health Interventions ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Long Read

ABSTRACT Carbapenem-resistant Enterobacterales (CRE) pose a significant threat to global public health. The most important mechanism for carbapenem resistance is the production of carbapenemases. Klebsiella pneumoniae carbapenemase (KPC) represents one of the main carbapenemases worldwide. Complex mechanisms of blaKPC dissemination have been reported in Colombia, a country with a high endemicity of carbapenem resistance. Here, we characterized the dynamics of dissemination of blaKPC gene among CRE infecting and colonizing patients in three hospitals localized in a highly endemic area of Colombia (2013 and 2015). We identified the genomic characteristics of KPC-producing Enterobacterales recovered from patients infected/colonized and reconstructed the dynamics of dissemination of blaKPC-2 using both short and long read sequencing. We found that spread of blaKPC-2 among Enterobacterales in the participating hospitals was due to intra- and interspecies horizontal gene transfer (HGT) mediated by promiscuous plasmids associated with transposable elements that was originated from a multispecies outbreak of KPC-producing Enterobacterales in a neonatal intensive care unit. The plasmids were detected in isolates recovered in other units within the same hospital and nearby hospitals. The gene “epidemic” was driven by IncN-pST15-type plasmids carrying a novel Tn4401b structure and non-Tn4401 elements (NTEKPC) in Klebsiella spp., Escherichia coli, Enterobacter spp., and Citrobacter spp. Of note, mcr-9 was found to coexist with blaKPC-2 in species of the Enterobacter cloacae complex. Our findings suggest that the main mechanism for dissemination of blaKPC-2 is HGT mediated by highly transferable plasmids among species of Enterobacterales in infected/colonized patients, presenting a major challenge for public health interventions in developing countries such as Colombia.

scholarly journals A Cluster of Colistin- and Carbapenem-Resistant Klebsiella pneumoniae Carrying blaNDM-1 and mcr-8.2

2019 ◽  
Vol 221 (Supplement_2) ◽  
pp. S237-S242 ◽  
Author(s):  
Ke Ma ◽  
Yu Feng ◽  
Lu Liu ◽  
Zhihong Yao ◽  
Zhiyong Zong
Keyword(s):  
Klebsiella Pneumoniae ◽  
Nucleotide Polymorphisms ◽  
Illumina Hiseq ◽  
Carbapenem Resistant ◽  
Interhospital Transfer ◽  
Transmissible Plasmid ◽  
New Variant ◽  
Long Read ◽  
Illumina Hiseq Platform ◽  
Resistant Strains

Abstract Background Klebsiella pneumoniae resistant to both carbapenems and colistin imposes severe challenges for management. In this study, we report a cluster of 5 carbapenem-resistant K pneumoniae clinical strains belonging to ST1 and K57 types, 4 of which were also resistant to colistin, from 2 hospitals. Methods The 5 strains were subjected to whole-genome sequencing (WGS) using the short-read Illumina HiSeq platform, and 2 strains were also selected for long-read WGS using MinION. Clonal relatedness of the 5 strains was determined based on single-nucleotide polymorphisms (SNPs). Conjugation experiments were performed to obtain self-transmissible plasmids. Results All 5 strains carried the carbapenemase-encoding gene blaNDM-1, whereas the 4 colistin-resistant strains also harbored a new variant of the mcr-8 colistin resistance gene, namely, mcr-8.2. MCR-8.2 differs from MCR-8.1 by four amino acid substitutions (A51V, A232S, N365Y, and N480K). mcr-8.2 was located on a large, hybrid, nonself-transmissible plasmid containing IncQ, IncR, and IncFII replicons, whereas blaNDM-1 was carried by self-transmissible IncX3 plasmids. Phylogenetic analysis based on SNPs revealed that the 5 strains were likely to have a common origin. Conclusions Both the intra- and interhospital transfer of strains carrying mcr-8 and blaNDM-1 were identified, which represents an emerging threat for clinical management and infection control.

scholarly journals Complete Sequence of ablaKPC-2-Harboring IncFIIK1Plasmid from a Klebsiella pneumoniae Sequence Type 258 Strain

2013 ◽  
Vol 57 (3) ◽  
pp. 1542-1545 ◽  
Author(s):  
Liang Chen ◽  
Kalyan D. Chavda ◽  
Roberto G. Melano ◽  
Michael R. Jacobs ◽  
Michael H. Levi ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
Nucleotide Sequence ◽  
Klebsiella Pneumoniae ◽  
York City ◽  
Complete Sequence ◽  
Sequence Type ◽  
Content Type ◽  
City Area ◽  
Carbapenem Resistant

ABSTRACTWe report the nucleotide sequence of a novelblaKPC-2-harboring IncFIIK1plasmid, pBK32179, isolated from a carbapenem-resistantKlebsiella pneumoniaeST258 strain from a New York City patient. pBK32179 is 165 kb long, consists of a large backbone of pKPN3-like plasmid, and carries an 18.5-kbblaKPC-2-containing element that is highly similar to plasmid pKpQIL. pBK32179-like plasmids were identified in 8.3% of strains in a collection of 96K. pneumoniaeisolates from hospitals in the New York City area.

scholarly journals Carbapenem-Resistant Klebsiella pneumoniae Strains Exhibit Diversity in Aminoglycoside-Modifying Enzymes, Which Exert Differing Effects on Plazomicin and Other Agents

2014 ◽  
Vol 58 (8) ◽  
pp. 4443-4451 ◽  
Author(s):  
Reem Almaghrabi ◽  
Cornelius J. Clancy ◽  
Yohei Doi ◽  
Binghua Hao ◽  
Liang Chen ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Bactericidal Activity ◽  
Sequence Type ◽  
Content Type ◽  
Molecular Assays ◽  
Carbapenem Resistant ◽  
Research Priority ◽  
Gentamicin Resistance

ABSTRACTWe measuredin vitroactivity of plazomicin, a next-generation aminoglycoside, and other aminoglycosides against 50 carbapenem-resistantKlebsiella pneumoniaestrains from two centers and correlated the results with the presence of various aminoglycoside-modifying enzymes (AMEs). Ninety-four percent of strains were sequence type 258 (ST258) clones, which exhibited 5ompK36genotypes; 80% and 10% of strains producedKlebsiella pneumoniaecarbapenemase 2 (KPC-2) and KPC-3, respectively. Ninety-eight percent of strains possessed AMEs, including AAC(6′)-Ib (98%), APH(3′)-Ia (56%), AAC(3)-IV (38%), and ANT(2″)-Ia (2%). Gentamicin, tobramycin, and amikacin nonsusceptibility rates were 40, 98, and 16%, respectively. Plazomicin MICs ranged from 0.25 to 1 μg/ml. Tobramycin and plazomicin MICs correlated with gentamicin MICs (r= 0.75 and 0.57, respectively). Plazomicin exerted bactericidal activity against 17% (1× MIC) and 94% (4× MIC) of strains. All strains with AAC(6′)-Ib were tobramycin-resistant; 16% were nonsusceptible to amikacin. AAC(6′)-Ib combined with another AME was associated with higher gentamicin, tobramycin, and plazomicin MICs than AAC(6′)-Ib alone (P= 0.01, 0.0008, and 0.046, respectively). The presence of AAC(3)-IV in a strain was also associated with higher gentamicin, tobramycin, and plazomicin MICs (P= 0.0006,P< 0.0001, andP= 0.01, respectively). The combination of AAC(6′)-Ib and another AME, the presence of AAC(3)-IV, and the presence of APH(3′)-Ia were each associated with gentamicin resistance (P= 0.0002, 0.003, and 0.01, respectively). In conclusion, carbapenem-resistantK. pneumoniaestrains (including ST258 clones) exhibit highly diverse antimicrobial resistance genotypes and phenotypes. Plazomicin may offer a treatment option against strains resistant to other aminoglycosides. The development of molecular assays that predict antimicrobial responses among carbapenem-resistantK. pneumoniaestrains should be a research priority.

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