scholarly journals Transmission Dynamics of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 Strains Carrying Capsular Loci KL64 and rmpA/rmpA2 Genes

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingying Kong ◽  
Qingyang Sun ◽  
Hangfei Chen ◽  
Mohamed S. Draz ◽  
Xinyou Xie ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Antimicrobial Agents ◽  
Therapeutic Option ◽  
Sequence Type ◽  
Transmission Dynamics ◽  
Virulence Plasmid ◽  
Virulence Determinants ◽  
Resistance Level ◽  
Carbapenem Resistant ◽  
Epidemiological Characteristics

The presence and dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP) often cause life-threatening infections worldwide, but the therapeutic option is limited. In this study, whole-genome sequencing (WGS) was applied to assess the epidemiological characteristics and transmission dynamics of CRKP isolates recovered from two fetal outbreaks of nosocomial infections. Between April 2016 and March 2018, a total of 70 isolates of K. pneumoniae were collected from sterile samples in a tertiary hospital in Hangzhou, China. The minimal inhibitory concentrations (MICs) of 21 antimicrobial agents were determined using the broth microdilution methods. Pulsed-field gel electrophoresis (PFGE) was performed on 47 CRKP isolates, and 16 clonally related isolates were further characterized by Illumina sequencing. In addition, the complete genome sequences of three representative isolates (KP12, KP36, and KP37) were determined by Oxford Nanopore sequencing. The K. pneumoniae isolates were recovered from patients diagnosed with pulmonary infection, cancer, or encephalopathy. For all CRKP isolates, PFGE separated three clusters among all strains. The most predominant PFGE cluster contained 16 isolates collected from patients who shared close hospital units and represented a potential outbreak. All 16 isolates showed an extremely high resistance level (≥87.5%) to 18 antimicrobials tested but remain susceptible to colistin (CST). Multiple antimicrobial resistance and virulence determinants, such as the carbapenem resistance gene blaKPC-2, and genes encoding the virulence factor aerobactin and the regulator of the mucoid phenotype (rmpA and rmpA2), were observed in the 16 CRKP isolates. These isolates belonged to sequence type 11 (ST11) and capsular serotype KL64. A core genome single nucleotide polymorphism (cgSNP)-based phylogenetic analysis indicated that the 16 CRKP isolates could be partitioned into two separate clades (≤15 SNPs), suggesting the two independent transmission scenarios co-occurred. Moreover, a high prevalence of IncFIB/IncHI1B type virulence plasmid with the iroBCDN locus deleted, and an IncFII/IncR type blaKPC-2-bearing plasmid was co-harbored in ST11-KL64 CRKP isolates. In conclusion, our data indicated that the nosocomial dissemination of ST11-KL64 CRKP clone is a potential threat to anti-infective therapy. The development of novel strategies for surveillance, diagnosis, and treatment of this high-risk CRKP clone is urgently needed.

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.

scholarly journals Aerobactin Seems To Be a Promising Marker Compared With Unstable RmpA2 for the Identification of Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae: In Silico and In Vitro Evidence

2021 ◽  
Vol 11 ◽  
Author(s):  
Chaitra Shankar ◽  
Soumya Basu ◽  
Binesh Lal ◽  
Sathiya Shanmugam ◽  
Karthick Vasudevan ◽  
...  
Keyword(s):  
High Risk ◽  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
In Silico ◽  
Fitness Cost ◽  
Virulence Plasmid ◽  
Virulence Determinants ◽  
Carbapenem Resistant ◽  
Antimicrobial Resistance Genes

BackgroundThe incidence of hypervirulent (hv) carbapenem-resistant (CR) Klebsiella pneumoniae (Kp) is increasing globally among various clones and is also responsible for nosocomial infections. The CR-hvKp is formed by the uptake of a virulence plasmid by endemic high-risk clones or by the uptake of plasmids carrying antimicrobial resistance genes by the virulent clones. Here, we describe CR-hvKp from India belonging to high-risk clones that have acquired a virulence plasmid and are phenotypically unidentified due to lack of hypermucoviscosity.MethodsTwenty-seven CRKp isolates were identified to possess rmpA2 by whole-genome sequencing; and resistance and virulence determinants were characterized. By in silico protein modeling (and validation), protein backbone stability analysis, and coarse dynamics study, the fitness of RmpA, RmpA2, and aerobactin-associated proteins-IucA and IutA, were determined to establish a reliable marker for clinical identification of CR-hvKp.ResultsThe CR-hvKp belonged to multidrug-resistant (MDR) high-risk clones such as CG11, CG43, ST15, and ST231 and carried OXA-232 as the predominant carbapenemase followed by NDM. The virulence plasmid belonged to IncHI1B replicon type and carried frameshifted and truncated rmpA and rmpA2. This resulted in a lack of hypermucoviscous phenotype. However, functional aerobactin was expressed in all high-risk clones. In silico analysis portrayed that IucA and IutA were more stable than classical RmpA. Furthermore, IucA and IutA had lower conformational fluctuations in the functional domains than the non-functional RmpA2, which increases the fitness cost of the latter for its maintenance and expression among CR-hvKp. Hence, RmpA and RmpA2 are likely to be lost among CR-hvKp owing to the increased fitness cost while coding for essential antimicrobial resistance and virulence factors.ConclusionIncreasing incidence of convergence of AMR and virulence is observed among K. pneumoniae globally, which warrants the need for reliable markers for identifying CR-hvKp. The presence of non-functional RmpA2 among high-risk clones highlights the significance of molecular identification of CR-hvKp. The negative string test due to non-functional RmpA2 among CR-hvKp isolates challenges phenotypic screening and faster identification of this pathotype. This can potentially be counteracted by projecting aerobactin as a stable, constitutively expressed, and functional marker for rapidly evolving CR-hvKp.

scholarly journals Genome-Based Analysis of a Sequence Type 1049 Hypervirulent Klebsiella pneumoniae Causing Bacteremic Neck Abscess

2021 ◽  
Vol 11 ◽  
Author(s):  
Peng Lan ◽  
Dongdong Zhao ◽  
Jiong Gu ◽  
Qiucheng Shi ◽  
Rushuang Yan ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genetic Background ◽  
Antimicrobial Agents ◽  
Allelic Diversity ◽  
Genomic Analysis ◽  
Sequence Type ◽  
Virulence Plasmid ◽  
Neck Abscess ◽  
Anatomic Locations

Hypervirulent Klebsiella pneumoniae (hvKP) has raised grave concerns in recent years and can cause severe infections with diverse anatomic locations including liver abscess, meningitis, and endophthalmitis. However, there is limited data about neck abscess caused by hvKP. A K. pneumoniae strain Kp_whw was isolated from neck abscess. We characterized the genetic background, virulence determinates of the strain by genomic analysis and dertermined the virulence level by serum resistance assay. Kp_whw belonged to sequence type (ST) 1049 K locus (KL) 5. Kp_whw showed hypermucoviscosity phenotype and was resistant to ampicillin but susceptible to the majority of the other antimicrobial agents. A pLVPK-like virulence plasmid and a chromosomal ICEKp5-like mobile genetic element were carried by Kp_whw, resulting in the risk of dissemination of hypervirulence. The strain exhibited relative higher level of core genome allelic diversity than accessory genome profile, in comparison to hvKP of K1/K2 serotype. Kp_whw was finally demonstrated as virulent as the ST23 K1 serotype hvKP strain NTUH-K2044 in vitro. In conclusion, this work elaborates the genetic background of a clinical hvKP strain with an uncommon ST, reinforcing our understanding of virulence mechanisms of hvKP.

scholarly journals Epidemiology and Clinical Significance of pLVPK-Like Virulence Plasmid in KPC-2-Producing Klebsiella Pneumoniae Infections in A Tertiary Hospital in Eastern China

2020 ◽  
Author(s):  
Min Xu ◽  
Qing Yang ◽  
Yanchao Liu ◽  
Xiao Chen ◽  
Haishen Kong ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Outcomes ◽  
Susceptibility Testing ◽  
Eastern China ◽  
Multivariable Analysis ◽  
Tertiary Hospital ◽  
Sequence Type ◽  
Virulence Plasmid ◽  
Carbapenem Resistant ◽  
Wide Dissemination

Abstract Background: By acquiring a pLVPK-like virulence plasmid (pVir), Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-kp) evolves to a hypervirulent variant, however, controversies exist. The aim of present study was to determine the prevalence, risk factors and clinical outcomes of patients infected with pVir+-KPC-kp.Methods: Between 2014 and 2018, 662 carbapenem-resistant K. pneumoniae (CRKP) were collected from a tertiary hospital in eastern China. The isolates were subjected to antimicrobial susceptibility testing, multilocus sequence typing and detection of blaKPC, pLVPK-related genetic loci (rmpA, rmpA2, iucA and iroN) to identify pVir+-KPC-kp. The clinical characteristics of pVir+-KPC-kp were retrospectively evaluated.Results: Of the 662 CRKP, 86.6% (573/662) were KPC-kp including 285 (49.7%) pVir+-KPC-kp and 288 (50.3%) pVir--KPC-kp. Notably, the prevalence of pVir+-KPC-kp by year increased remarkably from 2014 (19.5%, 8/41) to 2018 (60.0%, 90/150). Sequence type (ST) 11 was the most predominant ST, accounting for 88.9% of all pVir+-KPC-kp. For the 352 KPC-kp infection cases (186 with pVir+-KPC-kp and 166 with pVir--KPC-kp), multivariable analysis indicated neurosurgery (P =0.002) was independently associated with pVir+-KPC-kp infections. Although patients with pVir+-KPC-kp infections had higher incidence of septic shock (P =0.03), the two groups showed no significant differences in 7-day mortality (P =0.24) or 28-day mortality (P =0.75). Conclusions: A wide dissemination of pVir in ST11 KPC-kp has emerged in our region. Neurosurgery is an independent risk factor for acquisition of pVir+-KPC-kp infections. The mortality rates were similar between patients infected with pVir+-KPC-kp or pVir--KPC-kp, suggesting uncertain impact of pVir in clinical outcomes.

scholarly journals Emergence of OXA-232 Carbapenemase-Producing Klebsiella pneumoniae That Carries a pLVPK-Like Virulence Plasmid among Elderly Patients in China

2018 ◽  
Vol 63 (3) ◽  
Author(s):  
Lingbin Shu ◽  
Ning Dong ◽  
Jun Lu ◽  
Zhiwei Zheng ◽  
Jie Hu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Klebsiella Pneumoniae ◽  
Elderly Patients ◽  
Active Surveillance ◽  
Antimicrobial Therapy ◽  
Sequence Type ◽  
Virulence Plasmid ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Underlying Diseases

ABSTRACT This study reported the clonal dissemination of OXA-232-producing sequence type 15 (ST15) carbapenem-resistant Klebsiella pneumoniae among elderly patients in China. All patients were immunocompromised, suffered from multiple underlying diseases, and were hospitalized for a prolonged period; however, they slowly recovered on antimicrobial therapy. The blaOXA-232 gene was in a 6.1-kb ColKP3-type nonconjugative plasmid. The strains displayed a multidrug resistance phenotype and were not hypervirulent despite harboring a virulence plasmid. Active surveillance should be enforced to control further transmission.

Modeling of the transmission dynamics of carbapenem resistant Klebsiella pneumoniae in hospitals and design of control strategies

2021 ◽  
Author(s):  
Suttikiat Changruenngam ◽  
Charin Modchang ◽  
Dominique J. Bicout
Keyword(s):  
Klebsiella Pneumoniae ◽  
Antibiotic Treatment ◽  
Control Strategies ◽  
Transmission Dynamics ◽  
Global Public Health ◽  
Factors Affecting ◽  
Carbapenem Resistant ◽  
Number Of Treatment ◽  
Epidemiological Characteristics ◽  
The Impact

Abstract Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a major threat to global public health. Epidemiological and infection controls associated with CRKP are very challenging owing to several potential elements involved in a complicated cycle of transmission. Here, we proposed a comprehensive mathematical model to investigate the transmission dynamics of CRKP, determine factors affecting the prevalence, and evaluate the impact of interventions on the transmission. The model includes the essential compartments, which are uncolonized, asymptomatic colonized, symptomatic colonized, and relapsed patients. Moreover, the symptomatic colonized and relapsed patients are further classified into subpopulations according to their number of treatment failures or relapses. We found that the admission of colonized patients and the use of antibiotics have a significant influence on the endemic transmission. The proposed treatment efficacy, which is defined as a combination of the treatment duration and the probability of successful treatment, could also describe the effects of antibiotic treatment on the transmission. A high efficacy of the antibiotic treatment could significantly reduce the likelihood of readmission of a patient in the health care unit. In addition, our findings demonstrate that the CRKP transmission with different epidemiological characteristics needs to be controlled with distinct interventions.

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 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 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.

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