Multihospital Occurrence of Pan-Resistant Klebsiella pneumoniae Sequence Type 147 with an ISEcp1-Directed blaOXA-181 Insertion in the mgrB Gene in the United Arab Emirates

ABSTRACT The emergence of pan-resistant Klebsiella pneumoniae strains is an increasing concern. In the present study, we describe a cluster of 9 pan-resistant K. pneumoniae sequence type 147 (ST147) isolates encountered in 4 patients over nearly 1 year in 3 hospitals of the United Arab Emirates (UAE). The isolates exhibited highly similar genotypes. All produced chromosomally encoded OXA-181, and the majority also produced the NDM-5 carbapenemase. As with the previously described single isolate from the UAE, MS6671, the mgrB was disrupted by a functional, ISEcp1-driven bla OXA-181 insertion causing resistance to carbapenems. The mutation was successfully complemented with an intact mgrB gene, indicating that it was responsible for colistin resistance. bla NDM-5 was located within a resistance island of an approximately 100-kb IncFII plasmid carrying ermB, mph(A), bla TEM-1B, rmtB, bla NDM-5, sul1, aadA2, and dfrA12 resistance genes. Sequencing this plasmid (pABC143-NDM) revealed that its backbone was nearly identical to that of plasmid pMS6671E from which several resistance genes, including bla NDM-5, had been deleted. More extensive similarities of the backbone and the resistance island were found between pABC143C-NDM and the bla NDM-5-carrying IncFII plasmids of two K. pneumoniae ST147 isolates from South Korea, one of which was colistin resistant, and both also produced OXA-181. Notably, one of these strains was isolated from a patient transferred from the UAE. Our data show that this pan-resistant clone has an alarming capacity to maintain itself over an extended period of time and is even likely to be transmitted internationally.

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Colistin Resistance Gene mcr-8 in a High-Risk Sequence Type 15 Klebsiella pneumoniae Isolate from Kenya

Microbiology Resource Announcements ◽

10.1128/mra.00783-20 ◽

2020 ◽

Vol 9 (39) ◽

Author(s):

Cecilia Kyany’a ◽

Lillian Musila

Keyword(s):

High Risk ◽

Klebsiella Pneumoniae ◽

Resistance Gene ◽

Resistance Genes ◽

Multidrug Resistant ◽

Sequence Type ◽

Colistin Resistance ◽

Content Type ◽

Global Concern ◽

Hospitalized Patient

ABSTRACT The emergence and rise of mobile colistin resistance genes are of great global concern due to the ease of transfer of resistance to other bacteria. This report describes the genome of a colistin- and multidrug-resistant Klebsiella pneumoniae isolate bearing mcr-8, obtained from a hospitalized patient in Kenya.

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blaNDM-5-Bearing IncFII-Type Plasmids of Klebsiella pneumoniae Sequence Type 147 Transmitted by Cross-Border Transfer of a Patient

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02722-15 ◽

2016 ◽

Vol 60 (3) ◽

pp. 1932-1934 ◽

Cited By ~ 13

Author(s):

Juyoun Shin ◽

Jin Yang Baek ◽

Sun Young Cho ◽

Hee Jae Huh ◽

Nam Yong Lee ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

South Korea ◽

United Arab Emirates ◽

Sequence Type ◽

Content Type ◽

Korean Patient ◽

Cross Border ◽

Genetic Structures

The two plasmids extracted fromKlebsiella pneumoniaesequence type 147 (ST147) isolates were analyzed. The first isolate was obtained from a patient transferred from United Arab Emirates to South Korea. The second isolate was obtained from a Korean patient and was suspected to be transmitted from the first patient. Sequences of two plasmids were almost the same, and genetic structures, includingblaNDM-5, of these plasmids were similar to plasmids of NDM-1-producingEscherichia coliST131 isolates found in Europe.

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A Plasmid Bearing theblaCTX-M-15Gene and Phage P1-Like Sequences from a Sequence Type 11 Klebsiella pneumoniae Isolate

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00265-15 ◽

2015 ◽

Vol 59 (10) ◽

pp. 6608-6610 ◽

Cited By ~ 17

Author(s):

Juyoun Shin ◽

Kwan Soo Ko

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

South Korea ◽

Resistance Genes ◽

Sequence Type ◽

Content Type ◽

Plasmid Backbone

ABSTRACTPlasmid pKP12226 was extracted and analyzed from a CTX-M-15-producingKlebsiella pneumoniaesequence type 11 (ST11) isolate collected in South Korea. The plasmid represents chimeric characteristics consisting of a pIP1206-like backbone and lysogenized phage P1-like sequences. It bears a resistance region that includes resistance genes to several antibiotics and is different from previously characterized plasmids from South Korea bearingblaCTX-M-15. It may have resulted from recombination between anEscherichia coliplasmid backbone, ablaCTX-M-15-bearing resistance region, and lysogenized phage P1-like sequences.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00404-17 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 2

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.

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Loss of Hypermucoviscosity and Increased Fitness Cost in Colistin-Resistant Klebsiella pneumoniae Sequence Type 23 Strains

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00952-15 ◽

2015 ◽

Vol 59 (11) ◽

pp. 6763-6773 ◽

Cited By ~ 43

Author(s):

Myung-Jin Choi ◽

Kwan Soo Ko

Keyword(s):

Klebsiella Pneumoniae ◽

Lipid A ◽

Survival Rates ◽

Sequence Type ◽

Fitness Cost ◽

Colistin Resistance ◽

Content Type ◽

Expression Levels ◽

Maldi Tof ◽

Resistant Mutants

ABSTRACTIn this study, we investigated the effects of colistin resistance on virulence and fitness in hypermucoviscous (HV)Klebsiella pneumoniaesequence type 23 (ST23) strains. Colistin-resistant mutants were developed from three colistin-susceptible HVK. pneumoniaeST23 strains. The lipid A structures of strains were analyzed by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry. Changes in HV were investigated using the string test, and extracellular polysaccharide production was quantified. The expression levels of thephoQ,pmrD,pmrB,pbgP,magA, and p-rmpA2genes, serum resistance, and biofilm-forming activity were determined. The fitness of colistin-resistant mutants compared to that of the parental strains was examined by determining the competitive index (CI). The colistin-resistant mutants exhibited reduced HV, which was accompanied by decreased formation of capsular polysaccharides (CPS) and reduced expression of genes (magAand p-rmpA2). While there was enhanced expression ofpmrDandpbgPin all colistin-resistant derivatives, there were differences in the expression levels ofphoQandpmrBbetween strains. MALDI-TOF analysis detected the addition of aminoarabinose or palmitate to the lipid A moiety of lipopolysaccharide in the colistin-resistant derivatives. In addition, survival rates in the presence of normal human serum were decreased in the mutant strains, and CI values (0.01 to 0.19) indicated significant fitness defects in the colistin-resistant derivatives compared to the respective parental strains. In hypervirulent HVK. pneumoniaestrains, the acquisition of colistin resistance was accompanied by reduced CPS production, impaired virulence, and a significant fitness cost.

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IncP Plasmid Carrying Colistin Resistance Gene mcr-1 in Klebsiella pneumoniae from Hospital Sewage

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02229-16 ◽

2016 ◽

Vol 61 (2) ◽

Cited By ~ 36

Author(s):

Feifei Zhao ◽

Yu Feng ◽

Xiaoju Lü ◽

Alan McNally ◽

Zhiyong Zong

Keyword(s):

Klebsiella Pneumoniae ◽

Host Range ◽

Resistance Gene ◽

Insertion Sequence ◽

Sequence Type ◽

Broad Host Range ◽

Colistin Resistance ◽

Content Type ◽

Broad Host Range Plasmid ◽

Hospital Sewage

ABSTRACT A Klebsiella pneumoniae strain of sequence type 313 (ST313) recovered from hospital sewage was found carrying the plasmid-borne colistin resistance gene mcr-1, which was bracketed by two copies of the insertion sequence ISApl1 on a 57-kb self-transmissible IncP-type plasmid of a new IncP-1 clade. The carriage of mcr-1 on a self-transmissible broad-host-range plasmid highlights that mcr-1 has the potential to spread beyond the Enterobacteriaceae family.

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Colistin Resistance Caused by Inactivation of the MgrB Regulator Is Not Associated with Decreased Virulence of Sequence Type 258 KPC Carbapenemase-Producing Klebsiella pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02981-15 ◽

2016 ◽

Vol 60 (4) ◽

pp. 2509-2512 ◽

Cited By ~ 16

Author(s):

Fabio Arena ◽

Lucia Henrici De Angelis ◽

Antonio Cannatelli ◽

Vincenzo Di Pilato ◽

Marina Amorese ◽

...

Keyword(s):

Animal Model ◽

Klebsiella Pneumoniae ◽

Galleria Mellonella ◽

Sequence Type ◽

Capsular Type ◽

Clonal Lineage ◽

Colistin Resistance ◽

Content Type ◽

Content Model ◽

Clade 1

ABSTRACTUsing aGalleria mellonellaanimal model, we compared the virulence of two sequence type 258 (ST258) KPC-producingKlebsiella pneumoniaestrains, which were representative of the two clades of this clonal lineage, with that of isogenic colistin-resistantmgrBmutants. With both strains, themgrBmutants did not exhibit modification in virulence. In theG. mellonellamodel, the clade 1 strain (capsular typecps-1[wzi29, producing KPC-2]) was significantly more virulent than the clade 2 strain (capsular typecps-2[wzi154, producing KPC-3]).

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Characterization of a Multidrug-Resistant Porcine Klebsiella pneumoniae Sequence Type 11 Strain Coharboring blaKPC-2 and fosA3 on Two Novel Hybrid Plasmids

mSphere ◽

10.1128/msphere.00590-19 ◽

2019 ◽

Vol 4 (5) ◽

Cited By ~ 6

Author(s):

Wanjiang Zhang ◽

Yao Zhu ◽

Changzhen Wang ◽

Wenyu Liu ◽

Ruichao Li ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Resistance Genes ◽

Plasmid Stability ◽

Sequence Type ◽

Animal Origin ◽

Target Sequence ◽

Human Origin ◽

Content Type ◽

Isolation And Characterization

ABSTRACT The occurrence of carbapenemase-producing Enterobacteriaceae (CPE) poses a considerable risk for public health. The gene for Klebsiella pneumoniae carbapenemase-2 (KPC-2) has been reported in many countries worldwide, and KPC-2-producing strains are mainly of human origin. In this study, we identified two novel hybrid plasmids that carry either blaKPC-2 or the fosfomycin resistance gene fosA3 in the multiresistant K. pneumoniae isolate K15 of swine origin in China. The blaKPC-2-bearing plasmid pK15-KPC was a fusion derivative of an IncF33:A−:B− incompatibility group (Inc) plasmid and chromosomal sequences of K. pneumoniae (CSKP). A 5-bp direct target sequence duplication (GACTA) was identified at the boundaries of the CSKP, suggesting that the integration might have been due to a transposition event. The blaKPC-2 gene on pK15-KPC was in a derivative of ΔTn6296-1. The multireplicon fosA3-carrying IncN-IncR plasmid pK15-FOS also showed a mosaic structure, possibly originating from a recombination between an epidemic fosA3-carrying pHN7A8-like plasmid and a pKPC-LK30-like IncR plasmid. Stability tests demonstrated that both novel hybrid plasmids were stably maintained in the original host without antibiotic selection but were lost from the transformants after approximately 200 generations. This is apparently the first description of a porcine sequence type 11 (ST11) K. pneumoniae isolate coproducing KPC-2 and FosA3 via pK15-KPC and pK15-FOS, respectively. The multidrug resistance (MDR) phenotype of this high-risk K. pneumoniae isolate may contribute to its spread and its persistence. IMPORTANCE The global dissemination of carbapenem resistance genes is of great concern. Animals are usually considered a reservoir of resistance genes and an important source of human infection. Although carbapenemase-producing Enterobacteriaceae strains of animal origin have been reported increasingly, blaKPC-2-positive strains from food-producing animals are still rare. In this study, we first describe the isolation and characterization of a carbapenem-resistant Klebsiella pneumoniae ST11 isolate, strain K15, which is of pig origin and coproduces KPC-2 and FosA3 via two novel hybrid plasmids. Furthermore, our findings highlight that this ST11 Klebsiella pneumoniae strain K15 is most likely of human origin and could be easily transmitted back to humans via direct contact or food intake. In light of our findings, significant attention must be paid to monitoring the prevalence and further evolution of blaKPC-2-carrying plasmids among the Enterobacteriaceae strains of animal origin.

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Genomic Insights into Colistin-Resistant Klebsiella pneumoniae from a Tunisian Teaching Hospital

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01601-17 ◽

2017 ◽

Vol 62 (2) ◽

Cited By ~ 7

Author(s):

Nadia Jaidane ◽

Rémy A. Bonnin ◽

Wejdene Mansour ◽

Delphine Girlich ◽

Elodie Creton ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Teaching Hospital ◽

Resistance Genes ◽

Transmembrane Protein ◽

Health Concern ◽

Colistin Resistance ◽

Aminoglycoside Resistance ◽

Content Type ◽

Extended Spectrum Beta Lactamase ◽

A Genome

ABSTRACT The emergence of colistin-resistant Klebsiella pneumoniae (CoRKp) is a public health concern, since this antibiotic has become the last line of treatment for infections caused by multidrug-resistant (MDR) Gram negatives. In this study, we have investigated the molecular basis of colistin resistance in 13 MDR K. pneumoniae strains isolated from 12 patients in a teaching hospital in Sousse, Tunisia. Whole-genome sequencing (WGS) was used to decipher the molecular mechanism of colistin resistance and to identify the resistome of these CoRKp isolates. It revealed a genome of ca. 5.5 Mbp in size with a G+C content of 57%, corresponding to that commonly observed for K. pneumoniae. These isolates belonged to the 5 different sequence types (ST11, ST15, ST101, ST147, and ST392), and their resistome was composed of acquired β-lactamases, including extended-spectrum beta-lactamase and carbapenemase genes (bla CTX-M-15, bla OXA-204, bla OXA-48, and bla NDM-1 genes), aminoglycoside resistance genes [aac(6′)Ib-cr, aph(3″)-Ib, aph(6)-Id, and aac(3)-IIa], and fosfomycin (fosA), fluoroquinolone (qnr-like), chloramphenicol, trimethoprim, and tetracycline resistance genes. All of the isolates were identified as having a mutated mgrB gene. Mapping reads with reference sequences of the most common genes involved in colistin resistance revealed several modifications in mgrB, pmr, and pho operons (deletions, insertions, and substitutions) likely affecting the function of these proteins. It is worth noting that among the 12 patients, 10 were treated with colistin before the isolation of CoRKp. No plasmid encoding mcr-1 to mcr-5 genes was found in these isolates. This study corresponds to the first molecular characterization of a collection of CoRKp strains in Tunisia and highlights that the small-transmembrane protein MgrB is a main mechanism for colistin resistance in K. pneumoniae.

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Beneficial Chromosomal Integration of the Genes for CTX-M Extended-Spectrum β-Lactamase in Klebsiella pneumoniae for Stable Propagation

mSystems ◽

10.1128/msystems.00459-20 ◽

2020 ◽

Vol 5 (5) ◽

Author(s):

Eun-Jeong Yoon ◽

Bareum Gwon ◽

Changseung Liu ◽

Dokyun Kim ◽

Dongju Won ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

South Korea ◽

Acinetobacter Baumannii ◽

Resistance Gene ◽

Resistance Genes ◽

Chromosomal Location ◽

Chromosomal Integration ◽

Content Type ◽

Stable Propagation ◽

Extended Spectrum

Dominant F-type plasmids harboring the gene have been pointed out to be responsible for the dissemination of the CTX-M extended-spectrum-β-lactamase (ESBL)-producing K. pneumoniae. Recently, the emergence of K. pneumoniae isolates with the bla CTX-M gene in their chromosomes has been reported occasionally worldwide. Such a chromosomal location of the resistance gene could be beneficial for stable propagation, as was the Acinetobacter baumannii ST191 harboring chromosomal bla OXA-23 that is endemic to South Korea. Through the present study, particular clones were identified as having built-in resistance genes in their chromosomes, and the chromosomal integration events were tracked by assessing their genomes. The cefotaxime-resistant K. pneumoniae clones of this study were particularized as results of the fastidiousness for plasmids to acquire the bla CTX-M gene for securing the diversity and of the chromosomal addiction of the bla CTX-M gene for ensuring propagation.

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