Evolution of hypervirulence in carbapenem-resistant Klebsiella pneumoniae in China: a multicentre, molecular epidemiological analysis

2019 ◽  
Vol 75 (2) ◽  
pp. 327-336 ◽  
Author(s):  
Yawei Zhang ◽  
Longyang Jin ◽  
Pengwen Ouyang ◽  
Qi Wang ◽  
Ruobing Wang ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Virulence Genes ◽  
Galleria Mellonella ◽  
Infection Model ◽  
Epidemiological Analysis ◽  
Virulence Plasmids ◽  
Carbapenem Resistant ◽  
Resistance Plasmid ◽  
Serum Killing ◽  
Evolution Of Resistance

Abstract Objectives Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have been increasingly reported in China. Here, a multicentre, longitudinal surveillance study on CR-hvKP is described. Methods We retrospectively investigated carbapenem-resistant K. pneumoniae (CRKP) in 56 centres across China during 2015–17 and screened the virulence genes (iucA, iroN, rmpA and rmpA2) for the presence of virulence plasmids. Hypermucoviscosity, serum killing and Galleria mellonella lethality experiments were conducted to identify CR-hvKP among strains with all four virulence genes. Capsule typing, fitness and plasmid features of CR-hvKP were also investigated. Results A total of 1052 CRKP were collected. Among these, 34.2% (360/1052) carried virulence genes and 72 of them had all four of the virulence genes tested. Fifty-five (76.4%) were considered to be CR-hvKP using the G. mellonella infection model, with KPC-2-producing K64-ST11 being the most common type (80%, 44/55). Prevalence of CR-hvKP differed greatly between regions, with the highest in Henan (25.4%, 17/67) and Shandong (25.8%, 25/97). A significant increase in CR-hvKP among KPC-2-producing ST11 strains was observed, from 2.1% (3/141) in 2015 to 7.0% (23/329) in 2017 (P=0.045). Alarmingly, compared with classic CRKP, no difference in growth was found among CR-hvKP (P=0.7028), suggesting a potential risk for dissemination. The hybrid virulence and resistance-encoding plasmid evolved from pLVPK and the resistance plasmid harbouring blaKPC-2, indicating evolution existed between the hypervirulence and hyper-resistance plasmid. Conclusions CR-hvKP were more frequently detected than previously assumed, especially among KPC-2-producing ST11. Dissemination of hypervirulence could be extremely rapid due to limited fitness cost. Also, the evolution of resistance genes into hypervirulence plasmids was identified, presenting significant challenges for public health and infection control.

scholarly journals Comparison of Carbapenem-Resistant Klebsiella pneumoniae Strains Causing Intestinal Colonization and Extraintestinal Infections: Clinical, Virulence, and Molecular Epidemiological Characteristics

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenli Liao ◽  
Na Huang ◽  
Ying Zhang ◽  
Yao Sun ◽  
Tao Chen ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Virulence Genes ◽  
Galleria Mellonella ◽  
Infection Model ◽  
Klebsiella Pneumonia ◽  
Intestinal Colonization ◽  
Infection Group ◽  
Carbapenem Resistant ◽  
Significant Difference ◽  
Epidemiological Characteristics

Carbapenem-resistant Klebsiella pneumonia (CRKP) infections has become a concerning threat. However, knowledge regarding the characteristics of intestinal CRKP isolates is limited. This study aimed to investigate and compare the clinical, virulence and molecular epidemiological characteristics of intestinal colonization and extraintestinal infections CRKP strains. The clinical characteristics were investigated retrospectively. Polymerase chain reaction was used to investigate the capsular serotype, virulence genes and carbapenemase genes. Capsular polysaccharide quantification assay, serum resistance assay, biofilm formation assay, and infection model of Galleria mellonella larvae were performed to compare the virulence and pathogenicity. Besides, multilocus-sequence-typing (MLST) and pulsed-field-gel-electrophoresis (PFGE) were conducted to explore the homology of intestinal CRKP isolates. A total of 54 intestinal CRKP isolates were included. The main capsular serotypes were K14, K64, and K19. C-reactive protein and the proportion of ICU isolation of the infection group were significantly higher than that of the colonization group (P < 0.05). The carrier rates of various virulence genes of CRKP in the infection group were mostly higher than those in the colonization group, wherein the carrier rates of peg-344 and rmpA were significantly different (P < 0.05). There was no significant difference in capsular polysaccharides, antiserum ability, biofilm formation ability between the two group (P > 0.05), but the lethality of the infection group to Galleria mellonella was significantly higher than that of the colonization group (P < 0.05). The MLST categorized the 54 isolates into 13 different sequence types. PFGE revealed that homology among the 54 CRKP strains was <80%. This study suggested that the CRKP strains in the infection group had higher virulence than those in the colonization group. The development of CRKP isolates colonizing in the intestine should be addressed in future clinical surveillance.

scholarly journals Yersiniabactin, Colibactin and Wider Resistome Contribute to Enhanced Virulence and Persistence of KPC-2-Producing Klebsiella pneumoniae CG258 in South America

2018 ◽  
Author(s):  
Louise T. Cerdeira ◽  
Fernanda Esposito ◽  
Margaret M. C. Lam ◽  
Kelly L. Wyres ◽  
Ryan R. Wick ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
South America ◽  
Galleria Mellonella ◽  
Genomic Analysis ◽  
Public Health Issue ◽  
Infection Model ◽  
Veterinary Antibiotics ◽  
Carbapenem Resistant ◽  
Clonal Origin ◽  
Sequence Types

AbstractThe emergence and dissemination of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a worrisome public health issue compromising the treatment and outcome of infections caused by this pathogen. We performed a detailed virulome and resistome analysis of representative KPC- and/or CTX-M-producing K. pneumoniae belonging to clonal group (CG) 258 (sequence types ST11, ST258, ST340, ST437), circulating in Argentina, Brazil, Chile, Colombia and Peru; with further evaluation of the virulence behavior using the Galleria mellonella infection model. Genomic analysis of K. pneumoniae strains recovered from the human-animal-environment interface revealed a wide resistome characterized by the presence of genes and mutations conferring resistance to human and veterinary antibiotics, quaternary ammonium compounds (QACs) and heavy metals. Plasmid Inc typing revealed the presence of a wide diversity of replicon types with IncF, IncN, IncR and Col-like being frequently detected. Moreover, KPC-2-producing K. pneumoniae belonging to ST11 (KL-64 andKL-105) and ST340 (KL-15) carried multiple variants of distinct yersiniabactin siderophore (ybt) and/or genotoxic colibactin (clb) genes. In this regard, ICEKp3, ICEKp4 and ICEKp12 were identified in strains belonging to ST11 and ST340, recovered from Argentina, Brazil, Chile and Colombia; whereas ybt 17 and a novel ybt sequence type (YbST346) were identified together with clb in ICEKp10 structures from ST11 and ST258, from Brazil and Colombia, respectively. K. pneumoniae ST11 (ICEKp10/YbST346 and ICEKp4/ybt 10) strains killed 100% of wax moth larvae, in a similar way to hypervirulent K1/ST23 strain (ybt- and clb-negative) carrying the pLVPK-like plasmid, indicating enhanced virulence. In summary, our results indicate that yersiniabactin, colibactin and an expanded resistome have contributed to enhanced virulence and persistence of KPC-2-producing K. pneumoniae CG258 in South America. Therefore, active surveillance of hospital-associated lineages of K. pneumoniae should not only focus on clonal origin and antimicrobial resistance, but also on the virulence factors ybt and clb.

scholarly journals The Emergence of Novel Sequence Type Strains Reveals an Evolutionary Process of Intraspecies Clone Shifting in ICU-Spreading Carbapenem-Resistant Klebsiella pneumoniae

2021 ◽  
Vol 12 ◽  
Author(s):  
Dongdong Zhao ◽  
Qiucheng Shi ◽  
Dandan Hu ◽  
Li Fang ◽  
Yihan Mao ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Galleria Mellonella ◽  
Sequence Similarity ◽  
Public Health Problem ◽  
Infection Model ◽  
Virulence Determinants ◽  
Clinical Environment ◽  
Typing Method ◽  
Phylogenetic Structure ◽  
Carbapenem Resistant

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an urgent public health problem worldwide, and its rapid evolution in the clinical environment has been a major concern. A total of 99 CRKP isolates spreading in the intensive care unit (ICU) setting were included and subjected to whole-genome sequencing, and their sequence types (STs), serotype loci, and virulence determinants were screened based on genome data. The phylogenetic structure was reconstructed based on the core genome multilocus sequence typing method. Regions of recombination were assessed. Biofilm formation, serum resistance assays, and a Galleria mellonella infection model were used to evaluate strain virulence. A novel ST, designated ST4496, emerged in the ICU and spread for 6 months before its disappearance. ST4496 was closely related to ST11, with only a single-allele variant, and ST11 is the most dominant clinical clone in China. Recombination events occurred at capsule biosynthesis loci and divided the strains of ST11 and its derivative ST4496 into three clusters, including ST11-KL47, ST11-KL64, and ST4496-KL47. The phylogenetic structure indicated that ST11-KL47 was probably the origin of ST11-related strain evolution and presented more diversity in terms of both sequence similarity and phenotypes. ST4496-KL47 cluster strains presented less virulence than ST11-KL64, which was probably one of the factors preventing the former from spreading widely. In conclusion, ST4496-KL47 was probably derived from ST11-KL47 via intraspecies shifting but was less competitive than ST11-KL64, which also evolved from ST11-KL47 and developed increased virulence via capsule biosynthesis locus recombination. ST11-KL64 has the potential to be the predominant CRKP clone in China.

scholarly journals Phage Resistance Is Associated with Decreased Virulence in KPC-Producing Klebsiella pneumoniae of the Clonal Group 258 Clade II Lineage

2021 ◽  
Vol 9 (4) ◽  
pp. 762
Author(s):  
Lucia Henrici De Angelis ◽  
Noemi Poerio ◽  
Vincenzo Di Pilato ◽  
Federica De Santis ◽  
Alberto Antonelli ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Parental Strain ◽  
Bacterial Infections ◽  
Capsular Polysaccharide ◽  
Galleria Mellonella ◽  
Bacterial Pathogen ◽  
Phage Resistance ◽  
Infection Model ◽  
Lytic Phage ◽  
Susceptible Host

Phage therapy is now reconsidered with interest in the treatment of bacterial infections. A major piece of information for this application is the definition of the molecular targets exploited by phages to infect bacteria. Here, the genetic basis of resistance to the lytic phage φBO1E by its susceptible host Klebsiella pneumoniae KKBO-1 has been investigated. KKBO-1 phage-resistant mutants were obtained by infection at high multiplicity. One mutant, designated BO-FR-1, was selected for subsequent experiments, including virulence assessment in a Galleria mellonella infection model and characterization by whole-genome sequencing. Infection with BO-FR-1 was associated with a significantly lower mortality when compared to that of the parental strain. The BO-FR-1 genome differed from KKBO-1 by a single nonsense mutation into the wbaP gene, which encodes a glycosyltransferase involved in the first step of the biosynthesis of the capsular polysaccharide (CPS). Phage susceptibility was restored when BO-FR-1 was complemented with the constitutive wbaP gene. Our results demonstrated that φBO1E infects KKBO-1 targeting the bacterial CPS. Interestingly, BO-FR-1 was less virulent than the parental strain, suggesting that in the context of the interplay among phage, bacterial pathogen and host, the emergence of phage resistance may be beneficial for the host.

Emergence of ceftazidime/avibactam resistance in KPC-3-producing Klebsiella pneumoniae in vivo

2019 ◽  
Vol 74 (11) ◽  
pp. 3211-3216 ◽  
Author(s):  
Stephan Göttig ◽  
Denia Frank ◽  
Eleonora Mungo ◽  
Anika Nolte ◽  
Michael Hogardt ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Selection Pressure ◽  
Galleria Mellonella ◽  
Phenotypic Characterization ◽  
Infection Model ◽  
Development Of Resistance ◽  
Time Kill

Abstract Objectives The β-lactam/β-lactamase inhibitor combination ceftazidime/avibactam is active against KPC-producing Enterobacterales. Herein, we present molecular and phenotypic characterization of ceftazidime/avibactam resistance in KPC-3-producing Klebsiella pneumoniae that emerged in vivo and in vitro. Methods Sequence analysis of blaKPC-3 was performed from clinical and in vitro-generated ceftazidime/avibactam-resistant K. pneumoniae isolates. Time–kill kinetics and the Galleria mellonella infection model were applied to evaluate the activity of ceftazidime/avibactam and imipenem alone and in combination. Results The ceftazidime/avibactam-resistant clinical K. pneumoniae isolate revealed the amino acid change D179Y in KPC-3. Sixteen novel mutational changes in KPC-3 among in vitro-selected ceftazidime/avibactam-resistant isolates were described. Time–kill kinetics showed the emergence of a resistant subpopulation under selection pressure with either imipenem or ceftazidime/avibactam. However, combined selection pressure with imipenem plus ceftazidime/avibactam prevented the development of resistance and resulted in bactericidal activity. Concordantly, the G. mellonella infection model revealed that monotherapy with ceftazidime/avibactam is prone to select for resistance in vivo and that combination therapy with imipenem results in significantly better survival. Conclusions Ceftazidime/avibactam is a valuable antibiotic against MDR and carbapenem-resistant Enterobacterales. Based on time–kill kinetics as well as an in vivo infection model we postulate a combination therapy of ceftazidime/avibactam and imipenem as a strategy to prevent the development of ceftazidime/avibactam resistance in KPC-producing Enterobacterales in vivo.

scholarly journals An Outbreak of Carbapenem-Resistant Klebsiella Pneumoniae of K57 Capsular Serotype in an Emergency Intensive Care Unit of a Teaching Hospital in China

2020 ◽  
Author(s):  
Chunhong Shao ◽  
Yan Jin ◽  
Shuang Liu ◽  
Meijie Jiang ◽  
Shuping Zhao
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Klebsiella Pneumoniae ◽  
Teaching Hospital ◽  
Galleria Mellonella ◽  
Pulse Field ◽  
Carbapenem Resistant ◽  
Surrounding Environment ◽  
Antimicrobial Resistance Genes ◽  
Broth Microdilution Method

Abstract Background: Klebsiella pneumoniae is a common causative pathogen of nosocomial infections. The emergence of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) strains has further increased the threat posed by this bacterium. Here, we described an outbreak of 32 CR-hvKP isolates from the emergency intensive care unit (EICU) of a teaching hospital in China. Methods: From January 29, 2019 to March 11, 2019, 32 CRKp isolates were collected from 6 patients and their surrounding environment in EICU. Patient information including age, gender, length of EICU stay, diagnosis, treatment, and outcomes were obtained from electronic medical records. The isolates were identified using Vitek-MS system. The hypermucoviscosity phenotype was determined by the “string test”. Antimicrobial susceptibility testing was performed using VITEK 2 compact system, E-test or the broth microdilution method. All isolates were serotyped for K1, K2, K5, K20, K54, and K57 serotypes, antimicrobial resistance genes and twelve virulence-associated genes were screened using PCR and DNA sequencing. Multilocus sequence typing (MLST) and pulse-field gel electrophoresis (PFGE) were employed to characterize the genetic relationships among the CPKP isolates. The virulence capability of 11 CRKp isolates from 6 patients was evaluated through Galleria mellonella larva infection assay. Results: This outbreak involved 6 patients and lasted for 40 days. All 32 CR-hvKp isolates were obtained from 6 patients and their surrounding environment. PFGE showed that all 32 isolates belonged to one cluster, and MLST revealed that belonged to ST11. All isolates exhibited high resistance to β-lactam antibiotics, quinolones, and aminoglycosides. They were susceptible to ceftazidime/averbatan, tigecycline, and colistin. All 32 isolates harbored multiple resistance determinants, including blaKPC-2, blaSHV-11, blaTEM-1, rmtB, and qnrD. The serotype of all 32 isolates was K57 that was rarely reported. In the virulence gene analysis, all 32 isolates contained 6 virulence genes, namely, fimH, iucB, mrkD, rmpA, uge, and wabG. Infection assays demonstrated high mortality in the Galleria mellonella model. Following measures implemented by the hospital, the outbreak was controlled. The mortality rate was 83.3%.Conclusions: The epidemiology of CR-hvKP should be monitored closely to detect early indications of this emerging public health threat.

scholarly journals Carbapenemase Production and Epidemiological Characteristics of Carbapenem-Resistant Klebsiella pneumoniae in Western Chongqing, China

2022 ◽  
Vol 11 ◽  
Author(s):  
Wan Huang ◽  
Jisheng Zhang ◽  
Lingyi Zeng ◽  
Chengru Yang ◽  
Lining Yin ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Klebsiella Pneumoniae ◽  
Virulence Genes ◽  
Resistance Rate ◽  
Molecular Characteristics ◽  
Chain Reaction ◽  
Detection Rates ◽  
Carbapenem Resistant ◽  
Polymerase Chain ◽  
Epidemiological Characteristics

BackgroundThis study aimed to determine the molecular characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in a hospital in western Chongqing, southwestern China.MethodsA total of 127 unique CRKP isolates were collected from the Yongchuan Hospital of Chongqing Medical University, identified using a VITEK-2 compact system, and subjected to microbroth dilution to determine the minimal inhibitory concentration. Enterobacteriaceae intergenic repeat consensus polymerase chain reaction and multilocus sequence typing were used to analyze the homology among the isolates. Genetic information, including resistance and virulence genes, was assessed using polymerase chain reaction. The genomic features of the CRKP carrying gene blaKPC-2 were detected using whole-genome sequencing.ResultsST11 was the dominant sequence type in the homology comparison. The resistance rate to ceftazidime-avibactam in children was much higher than that in adults as was the detection rate of the resistance gene blaNDM (p < 0.0001). Virulence genes such as mrkD (97.6%), uge (96.9%), kpn (96.9%), and fim-H (84.3%) had high detection rates. IncF (57.5%) was the major replicon plasmid detected, and sequencing showed that the CRKP063 genome contained two plasmids. The plasmid carrying blaKPC-2, which mediates carbapenem resistance, was located on the 359,625 base pair plasmid IncFII, together with virulence factors, plasmid replication protein (rep B), stabilizing protein (par A), and type IV secretion system (T4SS) proteins that mediate plasmid conjugation transfer.ConclusionOur study aids in understanding the prevalence of CRKP in this hospital and the significant differences between children and adults, thus providing new ideas for clinical empirical use of antibiotics.

scholarly journals Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United States

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Victor I. Band ◽  
Sarah W. Satola ◽  
Richard D. Smith ◽  
David A. Hufnagel ◽  
Chris Bower ◽  
...  
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
Diagnostic Testing ◽  
Cladistic Analysis ◽  
The United States ◽  
Clinical Diagnostics ◽  
Infection Model ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Clinical Diagnostic

ABSTRACT Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States. IMPORTANCE Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy. Heteroresistance to colistin was more common than conventional resistance and was overwhelmingly misclassified as susceptibility by clinical diagnostic testing. Higher proportions of colistin heteroresistance observed in certain Enterobacter species and clustering among heteroresistant Klebsiella pneumoniae strains may inform colistin treatment recommendations. Overall, the rate of colistin nonsusceptibility was more than double the level detected by clinical diagnostics, suggesting that the prevalence of colistin nonsusceptibility among CRE may be higher than currently appreciated in the United States.

A Study of the Virulence Traits of Carbapenem-Resistant Klebsiella pneumoniae Isolates in a Galleria mellonella Model

2019 ◽  
Vol 25 (7) ◽  
pp. 1063-1071 ◽  
Author(s):  
Mahmoud A.F. Khalil ◽  
Raghda Hager ◽  
Fadwa Abd-El Reheem ◽  
Eman E. Mahmoud ◽  
Tamer Samir ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Galleria Mellonella ◽  
Carbapenem Resistant ◽  
Virulence Traits

scholarly journals A Sequence Type 23 Hypervirulent Klebsiella pneumoniae Strain Presenting Carbapenem Resistance by Acquiring an IncP1 blaKPC-2 Plasmid

2021 ◽  
Vol 11 ◽  
Author(s):  
Rushuang Yan ◽  
Ye Lu ◽  
Yiwei Zhu ◽  
Peng Lan ◽  
Shengnan Jiang ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Antimicrobial Agents ◽  
Carbapenem Resistance ◽  
High Serum ◽  
Sequence Type ◽  
Infection Model ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Molecular Features ◽  
Carbapenem Resistant

Hypervirulent Klebsiella pneumoniae strains are typically associated with severe infections and susceptible to most antimicrobial agents. In 2017, a carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) strain was isolated from the sputum of a chronic obstructive pulmonary disease (COPD) patient in Zhejiang, China. The goal of the present study was to characterize the molecular features of the CR-hvKP isolate ZJ27003 and its blaKPC-2-harboring plasmid p27003_KPC. Antimicrobial susceptibility was evaluated using the broth microdilution and agar dilution methods. String tests, serum-killing and mouse survival assays were performed to assess virulence, and plasmid conjugation was performed by filter mating. The complete genome sequence of ZJ27003 was acquired using a hybrid assembly of Illumina and Nanopore platform data. The sequence type (ST) of this CR-hvKP isolate was identified as ST23, which exhibits hypervirulence with high serum resistance and murine infection model. The strain is also resistant to carbapenems (imipenem, meropenem and ertapenem), aztreonam and cephalosporins. Additionally, the CR-hvKP isolate carries a 36,708-bp blaKPC-2-harboring plasmid, named p27003_KPC, belonging to the P1 incompatibility (Inc) group. The backbone of p27003_KPC is similar to that of a blaGES-5-harboring Pseudomonas aeruginosa plasmid, in which the blaGES-5 and its surrounding regions were replaced by a blaKPC-2-containing translocatable unit derived from Enterobacteriaceae. The results of a conjugation assay revealed that p27003_KPC can be transferred from K. pneumoniae to P. aeruginosa PAO1 and make the recipient resistant against carbapenem. The identification of a carbapenem-resistant hypervirulent K. pneumoniae isolate carrying and disseminating the blaKPC-2 gene highlights a severe threat to public health.

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