scholarly journals In VivoEmergence of Colistin Resistance in Klebsiella pneumoniae Producing KPC-Type Carbapenemases Mediated by Insertional Inactivation of the PhoQ/PhoPmgrBRegulator

2013 ◽  
Vol 57 (11) ◽  
pp. 5521-5526 ◽  
Author(s):  
Antonio Cannatelli ◽  
Marco Maria D'Andrea ◽  
Tommaso Giani ◽  
Vincenzo Di Pilato ◽  
Fabio Arena ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genomic Analysis ◽  
Negative Regulator ◽  
Resistant Isolate ◽  
Comparative Genomic ◽  
Colistin Resistance ◽  
Content Type ◽  
Insertional Inactivation ◽  
Resistant Mutants

ABSTRACTColistin is one of the few agents that retain activity against extensively drug-resistant strains ofKlebsiella pneumoniaeproducing KPC-type carbapenemases (KPC-KP). However, resistance to colistin is increasingly reported among KPC-KP. Comparative genomic analysis of a pair of sequential KPC-KP isolates from the same patient including a colistin-susceptible isolate (KKBO-1) and a colistin-resistant isolate (KKBO-4) selected after colistin exposure revealed that insertional inactivation of themgrBgene, encoding a negative regulator of the PhoQ/PhoP signaling system, is a genetic mechanism for acquired colistin resistance. The role ofmgrBinactivation in acquired colistin resistance was confirmed by complementation experiments with wild-typemgrB, which restored colistin susceptibility in KKBO-4, and by construction of anmgrBdeletion mutant from KKBO-1, which exhibited a colistin-resistant phenotype. InsertionalmgrBinactivation was also detected in 60% of colistin-resistant mutants selected from KKBO-1in vitro, following plating on colistin-containing medium, confirming the role (although not unique) of this mechanism in the emergence of acquired colistin resistance. In colistin-resistant mutants carrying insertional inactivation or deletion of themgrBgene, upregulated transcription ofphoP,phoQ, andpmrK(which is part of thepmrHFIJKLMoperon) was detected. These findings confirmed the MgrB regulatory role inK. pneumoniaeand were in agreement with the known association between upregulation of the PhoQ/PhoP system and activation of thepmrHFIJKLMoperon, which eventually leads to resistance to polymyxins by modification of the lipopolysaccharide target.

scholarly journals In VivoEvolution to Colistin Resistance by PmrB Sensor Kinase Mutation in KPC-Producing Klebsiella pneumoniae Is Associated with Low-Dosage Colistin Treatment

2014 ◽  
Vol 58 (8) ◽  
pp. 4399-4403 ◽  
Author(s):  
Antonio Cannatelli ◽  
Vincenzo Di Pilato ◽  
Tommaso Giani ◽  
Fabio Arena ◽  
Simone Ambretti ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genomic Analysis ◽  
Amino Acid Position ◽  
Comparative Genomic ◽  
Sensor Kinase ◽  
Wild Type ◽  
Colistin Resistance ◽  
Content Type ◽  
Before And After ◽  
Low Dosage

ABSTRACTColistin is a key drug for the treatment of infections caused by extensively drug-resistant strains ofEnterobacteriaceaeproducing carbapenemases. However, the emergence of colistin resistance is being increasingly reported, especially amongKlebsiella pneumoniaestrains producing KPC-type carbapenemases (KPC-KP). In this work, we investigated colistin-susceptible (KPB-1) and colistin-resistant (KPB-2) sequential isolates obtained from a patient with a KPC-KP infection before and after low-dosage colistin treatment, respectively. By using a next-generation sequencing approach and comparative genomic analysis of the two isolates, we detected in KPB-2 a nonsynonymous nucleotide substitution in the gene encoding the PmrB sensor kinase, resulting in a leucine-to-arginine substitution at amino acid position 82. Compared with KPB-1, KPB-2 exhibited upregulated transcription ofpmrAand ofpmrK, which is part of thepmrHFIJKLMoperon responsible for modification of the colistin lipopolysaccharide target. Complementation with wild-typepmrBin KPB-2 restored colistin susceptibility and reduced the transcription ofpmrAandpmrKto basal levels, while expression of PmrBL82Rin KPB-1 did not alter colistin susceptibility or upregulatepmrAandpmrKexpression, confirming the dominance of wild-type PmrB versus the PmrBL82Rmutant. The present results indicated that PmrB mutations mediating colistin resistance may be selected during low-dosage colistin treatment. The colistin-resistant phenotype of KPB-2 was stable for up to 50 generations in the absence of selective pressure and was not associated with a significant fitness cost in a competition experiment.

scholarly journals The Combination of Colistin and Doripenem Is Synergistic against Klebsiella pneumoniae at Multiple Inocula and Suppresses Colistin Resistance in anIn VitroPharmacokinetic/Pharmacodynamic Model

2012 ◽  
Vol 56 (10) ◽  
pp. 5103-5112 ◽  
Author(s):  
Zakuan Z. Deris ◽  
Heidi H. Yu ◽  
Kathryn Davis ◽  
Rachel L. Soon ◽  
Jovan Jacob ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Population Analysis ◽  
Multidrug Resistant ◽  
Pharmacodynamic Model ◽  
Resistant Isolate ◽  
Colistin Resistance ◽  
Bacterial Killing ◽  
Content Type

ABSTRACTMultidrug-resistant (MDR)Klebsiella pneumoniaemay require combination therapy. We systematically investigated bacterial killing with colistin and doripenem mono- and combination therapy against MDRK. pneumoniaeand emergence of colistin resistance. A one-compartmentin vitropharmacokinetic/pharmacodynamic model was employed over a 72-h period with two inocula (∼106and ∼108CFU/ml); a colistin-heteroresistant reference strain (ATCC 13883) and three clinical isolates (colistin-susceptible FADDI-KP032 [doripenem resistant], colistin-heteroresistant FADDI-KP033, and colistin-resistant FADDI-KP035) were included. Four combinations utilizing clinically achievable concentrations were investigated. Microbiological responses were examined by determining log changes and population analysis profiles (for emergence of colistin resistance) over 72 h. Against colistin-susceptible and -heteroresistant isolates, combinations of colistin (constant concentration regimens of 0.5 or 2 mg/liter) plus doripenem (steady-state peak concentration [Cmax] of 2.5 or 25 mg/liter over 8 h; half-life, 1.5 h) generally resulted in substantial improvements in bacterial killing at both inocula. Combinations were additive or synergistic against ATCC 13883, FADDI-KP032, and FADDI-KP033 in 9, 9, and 14 of 16 cases (4 combinations at 6, 24, 48, and 72 h) at the 106-CFU/ml inoculum and 14, 11, and 12 of 16 cases at the 108-CFU/ml inoculum, respectively. Combinations at the highest dosage regimens resulted in undetectable bacterial counts at 72 h in 5 of 8 cases (4 isolates at 2 inocula). Emergence of colistin-resistant subpopulations in colistin-susceptible and -heteroresistant isolates was virtually eliminated with combination therapy. Against the colistin-resistant isolate, colistin at 2 mg/liter plus doripenem (Cmax, 25 mg/liter) at the low inoculum improved bacterial killing. This investigation provides important information for optimization of colistin-doripenem combinations.

scholarly journals OmpK26, a Novel Porin Associated with Carbapenem Resistance in Klebsiella pneumoniae

2011 ◽  
Vol 55 (10) ◽  
pp. 4742-4747 ◽  
Author(s):  
Laura García-Sureda ◽  
Antonio Doménech-Sánchez ◽  
Mariette Barbier ◽  
Carlos Juan ◽  
Joan Gascó ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Outer Membrane Proteins ◽  
Systemic Infection ◽  
Carbapenem Resistance ◽  
Resistant Isolate ◽  
Identical Result ◽  
Sequencing Analysis ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACTClinical isolates ofKlebsiella pneumoniaeresistant to carbapenems are being isolated with increasing frequency. Loss of the expression of the major nonspecific porins OmpK35/36 is a frequent feature in these isolates. In this study, we looked for porins that could compensate for the loss of the major porins in carbapenem-resistant organisms. Comparison of the outer membrane proteins from twoK. pneumoniaeclinical isogenic isolates that are susceptible (KpCS-1) and resistant (KpCR-1) to carbapenems revealed the absence of OmpK35/36 and the presence of a new 26-kDa protein in the resistant isolate. An identical result was obtained when another pair of isogenic isolates that are homoresistant (Kpn-3) and heteroresistant (Kpn-17) to carbapenems were compared. Mass spectrometry and DNA sequencing analysis demonstrated that this new protein, designated OmpK26, is a small monomeric oligogalacturonate-specific porin that belongs to the KdgM family of porins. Insertion-duplication mutagenesis of the OmpK26 coding gene,yjhA, in the carbapenem-resistant, porin-deficient isolate KpCR-1 caused the expression of OmpK36 and the reversion to the carbapenem-susceptible phenotype, suggesting that OmpK26 is indispensable for KpCR-1 to lose OmpK36 and become resistant to these antibiotics. Moreover, loss of the major porin and expression of OmpK26 reducedin vitrofitness and attenuated virulence in a murine model of acute systemic infection. Altogether, these results indicate that expression of the oligogalacturonate-specific porin OmpK26 compensates for the absence of OmpK35/36 and allows carbapenem resistance inK. pneumoniaebut cannot restore the fitness of the microorganism.

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

2015 ◽  
Vol 59 (11) ◽  
pp. 6763-6773 ◽  
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.

scholarly journals Emergence and Evolution of Multidrug-Resistant Klebsiella pneumoniae with both blaKPC and blaCTX-M Integrated in the Chromosome

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Weihua Huang ◽  
Guiqing Wang ◽  
Robert Sebra ◽  
Jian Zhuge ◽  
Changhong Yin ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
De Novo ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Comparative Genomic ◽  
Type I ◽  
Content Type ◽  
Antimicrobial Resistance Genes

ABSTRACT The extended-spectrum-β-lactamase (ESBL)- and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant K. pneumoniae, we identified three clinical isolates, CN1, CR14, and NY9, carrying both bla CTX-M and bla KPC genes. The complete genomes of these three K. pneumoniae isolates were de novo assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9, bla CTX-M and bla KPC were carried on two different plasmids. In contrast, CN1 had one copy of bla KPC-2 and three copies of bla CTX-M-15 integrated in the chromosome, for which the bla CTX-M-15 genes were linked to an insertion sequence, ISEcp1, whereas the bla KPC-2 gene was in the context of a Tn4401a transposition unit conjugated with a PsP3-like prophage. Intriguingly, downstream of the Tn4401a-bla KPC-2-prophage genomic island, CN1 also carried a clustered regularly interspaced short palindromic repeat (CRISPR)-cas array with four spacers targeting a variety of K. pneumoniae plasmids harboring antimicrobial resistance genes. Comparative genomic analysis revealed that there were two subtypes of type I-E CRISPR-cas in K. pneumoniae strains and suggested that the evolving CRISPR-cas, with its acquired novel spacer, induced the mobilization of antimicrobial resistance genes from plasmids into the chromosome. The integration and dissemination of multiple copies of bla CTX-M and bla KPC from plasmids to chromosome depicts the complex pandemic scenario of multidrug-resistant K. pneumoniae. Additionally, the implications from this study also raise concerns for the application of a CRISPR-cas strategy against antimicrobial resistance.

scholarly journals Phenylacetic Acid Catabolism and Its Transcriptional Regulation in Corynebacterium glutamicum

2012 ◽  
Vol 78 (16) ◽  
pp. 5796-5804 ◽  
Author(s):  
Xi Chen ◽  
Thomas A. Kohl ◽  
Christian Rückert ◽  
Dmitry A. Rodionov ◽  
Ling-Hao Li ◽  
...  
Keyword(s):  
Corynebacterium Glutamicum ◽  
Phenylacetic Acid ◽  
Specific Binding ◽  
Genomic Analysis ◽  
Negative Regulator ◽  
Comparative Genomic ◽  
Promoter Regions ◽  
Mobility Shift ◽  
Content Type ◽  
Transcription Regulator

ABSTRACTThe industrially important organismCorynebacterium glutamicumhas been characterized in recent years for its robust ability to assimilate aromatic compounds. In this study,C. glutamicumstrain AS 1.542 was investigated for its ability to catabolize phenylacetic acid (PAA). Thepaagenes were identified; they are organized as a continuouspaagene cluster. The type strain ofC. glutamicum, ATCC 13032, is not able to catabolize PAA, but the recombinant strain ATCC 13032/pEC-K18mob2::paagained the ability to grow on PAA. ThepaaRgene, encoding a TetR family transcription regulator, was studied in detail. Disruption ofpaaRin strain AS 1.542 resulted in transcriptional increases of allpaagenes. Transcription start sites and putative promoter regions were determined. An imperfect palindromic motif (5′-ACTNACCGNNCGNNCGGTNAGT-3′; 22 bp) was identified in the upstream regions ofpaagenes. Electrophoretic mobility shift assays (EMSA) demonstrated specific binding of PaaR to this motif, and phenylacetyl coenzyme A (PA-CoA) blocked binding. It was concluded that PaaR is the negative regulator of PAA degradation and that PA-CoA is the PaaR effector. In addition, GlxR binding sites were found, and binding to GlxR was confirmed. Therefore, PAA catabolism inC. glutamicumis regulated by the pathway-specific repressor PaaR, and also likely by the global transcription regulator GlxR. By comparative genomic analysis, we reconstructed orthologous PaaR regulons in 57 species, including species ofActinobacteria,Proteobacteria, andFlavobacteria, that carry PAA utilization genes and operate by conserved binding motifs, suggesting that PaaR-like regulation might commonly exist in these bacteria.

scholarly journals Characterization and Comparative Genomic Analysis of a Novel Bacteriophage, SFP10, Simultaneously Inhibiting both Salmonella enterica and Escherichia coli O157:H7

2011 ◽  
Vol 78 (1) ◽  
pp. 58-69 ◽  
Author(s):  
Minjung Park ◽  
Ju-Hoon Lee ◽  
Hakdong Shin ◽  
Minsik Kim ◽  
Jeongjoon Choi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Salmonella Enterica ◽  
Burst Size ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
Tail Fiber ◽  
Content Type ◽  
E Coli ◽  
Development Of Resistance

ABSTRACTSalmonella entericaandEscherichia coliO157:H7 are major food-borne pathogens causing serious illness. Phage SFP10, which revealed effective infection of bothS. entericaandE. coliO157:H7, was isolated and characterized. SFP10 contains a 158-kb double-stranded DNA genome belonging to the Vi01 phage-like familyMyoviridae.In vitroadsorption assays showed that the adsorption constant rates to bothSalmonella entericaserovar Typhimurium andE. coliO157:H7 were 2.50 × 10−8ml/min and 1.91 × 10−8ml/min, respectively. One-step growth analysis revealed that SFP10 has a shorter latent period (25 min) and a larger burst size (>200 PFU) than ordinaryMyoviridaephages, suggesting effective host infection and lytic activity. However, differential development of resistance to SFP10 inS.Typhimurium andE. coliO157:H7 was observed; bacteriophage-insensitive mutant (BIM) frequencies of 1.19 × 10−2CFU/ml forS.Typhimurium and 4.58 × 10−5CFU/ml forE. coliO157:H7 were found, indicating that SFP10 should be active and stable for control ofE. coliO157:H7 with minimal emergence of SFP10-resistant pathogens but may not be forS.Typhimurium. Specific mutation ofrfaLinS.Typhimurium andE. coliO157:H7 revealed the O antigen as an SFP10 receptor for both bacteria. Genome sequence analysis of SFP10 and its comparative analysis with homologousSalmonellaVi01 andShigellaphiSboM-AG3 phages revealed that their tail fiber and tail spike genes share low sequence identity, implying that the genes are major host specificity determinants. This is the first report identifying specific infection and inhibition ofSalmonellaTyphimurium andE. coliO157:H7 by a single bacteriophage.

scholarly journals MgrB Inactivation Is a Common Mechanism of Colistin Resistance in KPC-Producing Klebsiella pneumoniae of Clinical Origin

2014 ◽  
Vol 58 (10) ◽  
pp. 5696-5703 ◽  
Author(s):  
Antonio Cannatelli ◽  
Tommaso Giani ◽  
Marco Maria D'Andrea ◽  
Vincenzo Di Pilato ◽  
Fabio Arena ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Point Mutations ◽  
Multidrug Resistant ◽  
Common Mechanism ◽  
Colistin Resistance ◽  
Modification System ◽  
Content Type ◽  
Insertional Inactivation ◽  
Different Types ◽  
Intragenic Deletions

ABSTRACTKlebsiella pneumoniaestrains producing KPC-type carbapenemases (KPC-KP) are challenging multidrug-resistant pathogens due to their extensively drug-resistant phenotypes and potential for epidemic dissemination in health care settings. Colistin is a key component of the combination antimicrobial regimens used for treatment of severe KPC-KP infections. We previously reported that insertional inactivation of themgrBgene, encoding a negative-feedback regulator of the PhoQ-PhoP signaling system, can be responsible for colistin resistance in KPC-KP, due to the resulting upregulation of the Pmr lipopolysaccharide modification system. In this work we investigated the status of themgrBgene in a collection of 66 colistin-resistant nonreplicate clinical strains of KPC-KP isolated from different hospitals in Italy and Greece. Overall, 35 strains (53%) exhibited alterations of themgrBgene, including insertions of different types of mobile elements (IS5-like, IS1F-like, or ISKpn14), nonsilent point mutations, and small intragenic deletions. Four additional strains had a larger deletion of themgrBlocus, while the remaining 27 strains (41%) did not showmgrBalterations. Transcriptional upregulation of thephoQandpmrKgenes (part of thephoPQandpmrHFIJKLMoperon, respectively) was observed in all strains withmgrBalterations. Complementation experiments with a wild-typemgrBgene restored colistin susceptibility and basal expression levels ofphoQandpmrKgenes in strains carrying different types ofmgrBalterations. The present results suggest thatmgrBalteration can be a common mechanism of colistin resistance among KPC-KP in the clinical setting.

scholarly journals Phage Selective Pressure Reduces Virulence of Hypervirulent Klebsiella pneumoniae Through Mutation of the wzc Gene

2021 ◽  
Vol 12 ◽  
Author(s):  
Lingjie Song ◽  
Xianggui Yang ◽  
Jinwei Huang ◽  
Xiaokui Zhu ◽  
Guohui Han ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genomic Analysis ◽  
Resistant Bacteria ◽  
Comparative Genomic ◽  
Wild Type ◽  
Bacteriophage Therapy ◽  
Deletion Mutations ◽  
Invasive Infections

Hypervirulent Klebsiella pneumoniae (hvKp), one of the major community-acquired pathogens, can cause invasive infections such as liver abscess. In recent years, bacteriophages have been used in the treatment of K. pneumoniae, but the characteristics of the phage-resistant bacteria produced in the process of phage therapy need to be evaluated. In this study, two Podoviridae phages, hvKpP1 and hvKpP2, were isolated and characterized. In vitro and in vivo experiments demonstrated that the virulence of the resistant bacteria was significantly reduced compared with that of the wild type. Comparative genomic analysis of monoclonal sequencing showed that nucleotide deletion mutations of wzc and wcaJ genes led to phage resistance, and the electron microscopy and mucoviscosity results showed that mutations led to the loss of the capsule. Meanwhile, animal assay indicated that loss of capsule reduced the virulence of hvKp. These findings contribute to a better understanding of bacteriophage therapy, which not only can kill bacteria directly but also can reduce the virulence of bacteria by phage screening.

scholarly journals Complete Nucleotide Sequences ofblaKPC-4- andblaKPC-5-Harboring IncN and IncX Plasmids from Klebsiella pneumoniae Strains Isolated in New Jersey

2012 ◽  
Vol 57 (1) ◽  
pp. 269-276 ◽  
Author(s):  
Liang Chen ◽  
Kalyan D. Chavda ◽  
Henry S. Fraimow ◽  
José R. Mediavilla ◽  
Roberto G. Melano ◽  
...  
Keyword(s):  
New Jersey ◽  
Klebsiella Pneumoniae ◽  
Sequence Similarity ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Comparative Genomic ◽  
Bacterial Strains ◽  
Gene Encoding ◽  
Content Type ◽  
Plasmid Backbone

ABSTRACTKlebsiella pneumoniaecarbapenemase (KPC)-producingEnterobacteriaceaehave emerged as major nosocomial pathogens.blaKPC, commonly located on Tn4401, is found in Gram-negative bacterial strains, with the two most common variants,blaKPC-2andblaKPC-3, identified in plasmids with diverse genetic backgrounds. In this study, we examinedblaKPC-4- andblaKPC-5-bearing plasmids recovered from twoK. pneumoniaestrains, which were isolated from a single New Jersey hospital in 2005 and 2006, respectively. IncN plasmid pBK31551 is 84 kb in length and harborsblaKPC-4,blaTEM-1,qnrB2,aac(3)-Ib,aph(3′)-I,qacF,qacEΔ1,sul1, anddfrA14, which confer resistance to β-lactams, quinolones, aminoglycosides, quaternary ammonium compounds, and co-trimoxazole. The conserved regions within pBK31551 are similar to those of other IncN plasmids. Surprisingly, analysis of the Tn4401sequence revealed a large IS110- and Tn6901-carrying element (8.3 kb) inserted into theistAgene, encoding glyoxalase/bleomycin resistance, alcohol dehydrogenase, andS-formylglutathione hydrolase. Plasmid pBK31567 is 47 kb in length and harborsblaKPC-5,dfrA5,qacEΔ1, andsul1. pBK31567 belongs to a novel IncX subgroup (IncX5) and possesses a highly syntenic plasmid backbone like other IncX plasmids; however, sequence similarity at the nucleotide level is divergent. TheblaKPC-5gene is carried on a Tn4401element and differs from the genetic environment ofblaKPC-5described inPseudomonas aeruginosastrain P28 from Puerto Rico. This study underscores the genetic diversity of multidrug-resistant plasmids involved in the spread ofblaKPCgenes and highlights the mobility and plasticity of Tn4401. Comparative genomic analysis provides new insights into the evolution and dissemination of KPC plasmids belonging to different incompatibility groups.

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