Clinical evolution of ST11 carbapenem resistant and hypervirulent Klebsiella pneumoniae.
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ABSTRACT:
SUBMITTER: Xie M
PROVIDER: S-EPMC8169677 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has recently aroused increasing attention, especially ST11, the predominant CRKP clone in China. Here, we report a case of hv-CRKP-associated infection and reveal the in-host evolution of its mechanism of resistance to tigecycline and polymyxin under clinical therapy. A total of 11 K. pneumoniae carbapenemase (KPC)-producing CRKP strains were consecutively isolated from a male patient who suffered from continuous and multisite infections. String and antimicrobial susceptibility tests identified seven hypermucoviscous strains and three tigecycline-resistant and four colistin-resistant strains. Galleria mellonella larvae infection model confirmed the hypervirulence. Pulsed-field gel electrophoresis (PFGE) separated three PFGE clusters among all strains, and further Southern blotting detected that blaKPC-2 was located on the same-sized plasmid. Whole-genome sequencing showed that all strains belonged to the hv-CRKP ST11-KL64 clone. Diverse hypervirulence factors and resistance genes were identified. Further sequencing with the Nanopore platform was performed on the CRKP-Urine1 strain, which contained one virulence plasmid (pVi-CRKP-Urine1) and two resistance plasmids (pKPC-CRKP-Urine1 and pqnrS1-CRKP-Urine1). The gene mutations responsible for tigecycline or colistin resistance were then amplified with PCR followed by sequencing, which indicated that mutations of ramR and lon were the potential loci for tigecycline resistance and that the pmrB, phoQ and mgrB genes for colistin resistance. A novel frameshift mutation of lon was identified in the high-level tigecycline-resistant strain (MIC, 128 mg/L). The results indicate that the hypervirulent ST11-KL64 clone is a potential threat to antiinfection treatment and is capable of rapid and diverse evolution of resistance during tigecycline and polymyxin treatment.
| S-EPMC8205050 | biostudies-literature
Project description:Sequence type 36 (ST36) Klebsiella pneumoniae is distributed worldwide. We found an ST36 K. pneumoniae clinical isolate that was carbapenem resistant, carried blaKPC-2, had mucoid regulator gene rmpA, and exhibited high virulence. The finding suggests the emergence of carbapenem-resistant hypervirulent K. pneumoniae of ST36, and surveillance of carbapenem-resistant hypervirulent K. pneumoniae is required.
| S-EPMC6021629 | biostudies-literature
Project description:Background: Multidrug-resistant bacteria, especially those with high virulence, are an emerging problem in clinical settings.Methods: We conducted a multicentre epidemiological and comparative genomic analysis on the evolution, virulence and antimicrobial resistance of carbapenem-resistant Enterobacteriaceae in patients with bacterial liver abscesses from 2012 to 2016.Results: A total of 477 bacterial isolates were collected. Enterobacteriaceae were the main pathogen (89.3%) with K. pneumoniae (52.4%) predominating followed by Escherichia coli (26.8%). All CRKps (3.2%) were of sequence type (ST) 11 and serotypes K47 or K64, and simultaneously possessed acquired blaKPC-2/blaKPC-5 and blaCTX-M-65 together with the multidrug transporter EmrE. Seven Hv-CRKps (five ST11-K47, two ST11-K64) were confirmed by bacteriological test, neutrophil killing assay and Galleria mellonella infection model. Genomic analysis indicated that the emergence of one ST11-K64 Hv-CRKp strain was related to the acquisition of rmpA/rmpA2 genes and siderophore gene clusters, while ST11-K47 Hv-CRKp lacked these traditional virulence genes. Further complete genome analysis of one ST11-K47 Hv-CRKp strain, R16, showed that it acquired a rare plasmid (pR16-Hv-CRKp1) carrying blaKPC-2, blaSHV-12, blaTEM-1, blaCTX-M-65, rmtB and a predicted virulence gene R16_5486 simultaneously.Conclusion: The emergence of the ST11-K47/K64 Hv-CRKps, which are simultaneously multidrug-resistant and hypervirulent, requires urgent control measures to be implemented.
| S-EPMC7034084 | biostudies-literature
Project description:We report an outbreak of carbapenemase-producing hypervirulent Klebsiella pneumoniae in two hospitals that undergo frequent patient transfers. Analysis of 11 completely assembled genomes showed that the bacteria were ST11-K64 strains. Moreover, 12 single nucleotide polymorphisms (SNPs) identified the strains as having originated from the same cluster, and were also indicative of the interhospital transmission of infection. Five plasmids were assembled in each of the strains. One plasmid carried several virulence genes, including the capsular polysaccharide regulators rmpA and rmpA2. Two others carried antimicrobial-resistance genes, including one for carbapenem resistance, bla KPC-2. Comparative genomic analysis indicated the occurrence of frequent and rapid gain and loss of genomic content along transmissions and the co-existence of progeny strains in the same ward. A 10-kbp fragment harboring antimicrobial resistance-conferring genes flanked by insert sequences was missing in a plasmid from strain KP20194c in patient 3, and this strain also likely subsequently infected patient 4. However, strains containing the 10-kbp fragment were also isolated from the ward environment at approximately the same time, and harbored different chromosome indels. Tn1721 and multiple additional insert sequence-mediated transpositions were also seen. These results indicated that there is a rapid reshaping and diversification of the genomic pool of K. pneumoniae facilitated by mobile genetic elements, even a short time after outbreak onset. ST11-K64 CR-hvKP strains have the potential to become new significant superbugs and a threat to public health.
| S-EPMC7688671 | biostudies-literature
Project description:We report the identification of a carbapenem-resistant, hypervirulent Klebsiella pneumoniae (hvKp) strain which produced the carbapenemase VIM-1. Genomic analysis showed that the strain belonged to sequence type ST23 and serotype K1, a major hvKp clone, and harbored three resistance-encoding plasmids. Among them, a bla VIM-1-bearing plasmid was found to possess a mosaic structure presumably generated by multiple gene mobilization events. This finding indicates that hvKp actively acquires mobile resistance-encoding elements, facilitating simultaneous expression of hypervirulence and carbapenem-resistance.
| S-EPMC6709456 | biostudies-literature
Project description:BACKGROUND:Carbapenem-resistant hypervirulent Klebsiella pneumoniae strains have recently come into existence worldwide; however, researchers in northeast China are not aware of their clinical features and molecular characteristics. METHODS:Here, the molecular and virulent characteristics of 44 carbapenem-resistant K. pneumoniae (CRKP) isolates collected from January 2015 to December 2017 were studied. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were carried out to define the clonal relatedness among the isolates. PCR and capsular serotyping of the virulence-associated genes, as well as biofilm formation and serum complement-mediated killing assays, were employed to determine the virulent potential. The genomic features and associated mobile genetic elements of JmsCRE57 were detected by whole genome sequencing. RESULTS:The only positive isolate was JmsCRE57, which belonged to the ST375 serotype K2 that expressed uge, mrkD, fimH, kpn, aerobactin and rmpA virulence-associated genes and showed strong biofilm formation and serum sensitivity. Sequencing results showed that the JmsCRE57 genome mainly consisted of a circular chromosome, three antimicrobial resistant plasmids and a virulent plasmid. The antimicrobial resistant plasmid expressing blaKPC-2, blaCTX-M-15, aph(3″)-Ib, aph(6)-Id, qnrB1, aac(3)-IIa, aac(6')-Ib-cr, blaOXA-1, blaTEM-1B, catB4, sul2, dfrA14 and blaSHV-99. The virulent plasmid belonged to the IncHI1B group, which is mainly composed of mucoid phenotype genes and siderophore-associated genes. The remaining CRKP strains that expressed uge, fimH, mrkD and kpn virulence-associated genes were not successfully typed. CONCLUSION:Our results provide new insights on the epidemiology of carbapenem-resistant K2 hypervirulent K. pneumoniae ST375 and CRKP ST76 strains in northeast China, which may help control their future outbreaks.
| S-EPMC7331116 | biostudies-literature
Project description:Hypervirulent Klebsiella pneumoniae strains have been increasingly reported worldwide, and there is emergence of carbapenem resistance among them. Here, we report the genome sequences of three carbapenem-resistant hypervirulent K. pneumoniae isolates isolated from bacteremic patients at a tertiary-care center in South India.
| S-EPMC5146430 | biostudies-literature
Project description:Objective:The emergence of carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKp) strains poses a significant public threat, and effective antimicrobial therapy is urgently needed. Recent studies indicated that apramycin is a potent antibiotic with good activity against a range of multi-drug resistant pathogens. In this study, we evaluated the in vitro activity of apramycin against clinical CR-hvKp along with carbapenem-resistant non-hvKp (CR-non-hvKp) isolates. Methods:Broth microdilution method was used to evaluate the in vitro activities of apramycin, gentamicin, amikacin, imipenem, meropenem, doripenem, ertapenem and other comparator "last-resort" antimicrobial agents, including ceftazidime-avibactam, colistin and tigecycline, against eighty-four CR-hvKp and forty CR-non-hvKp isolates collected from three Chinese hospitals. Multilocus Sequence typing (MLST), molecular capsule typing (wzi sequencing) and antimicrobial resistance genes were examined by PCR and Sanger sequencing. Pulsed-field gel electrophoresis and next generation sequencing were conducted on selected isolates. Results:Among the 84 CR-hvKp isolates, 97.6, 100, 97.6, and 100% were resistant to imipenem, meropenem, doripenem and ertapenem, respectively. Apramycin demonstrated an MIC50/MIC90 of 4/8 ?g/mL against the CR-hvKp isolates. In contrast, the MIC50/MIC90 for amikacin and gentamicin were >64/>64 ?g/mL. All CR-hvKp isolates were susceptible to ceftazidime-avibactam, colistin and tigecycline with the MIC50/MIC90 values of 0.5/1, 0.25/0.5, 1/1, respectively. For CR-non-hvKp, The MIC50/90 values for apramycin, gentamicin and amikacin were 2/8, >64/>64, and >64/>64 ?g/mL, respectively. There were no statistical significance in the resistance rates of antimicrobial agents between CR-hvKp and CR-non-hvKp groups (p > 0.05). Genetic analysis revealed that all CR-hvKp isolates harbored bla KPC-2, and 94% (n = 79) belong to the ST11 high-risk clone. 93.6% (44/47) of amikacin or gentamicin resistant strains carried 16S rRNA methyltransferases gene rmtB. Conclusion:Apramycin demonstrated potent in vitro activity against CR-hvKp isolates, including those were resistant to amikacin or gentamicin. Further studies are needed to evaluate the applicability of apramycin to be used as a therapeutic antibiotic against CR-hvKp infections.
| S-EPMC7083131 | biostudies-literature
Project description:The recent convergence of genetic elements encoding phenotypic carbapenem-resistance and hypervirulence within a single Klebsiella pneumoniae host strain represents a major public concern. To obtain a better understanding of the genetic characteristic of this emerging 'superbug', the complete genomes of 3 isolates of ST11 carbapenemase-producing hypervirulent K. pneumoniae were generated using the Oxford nanopore MinION platform. Comparative whole-genome analysis identified 13 SNPs and 3 major regions of indels in the chromosomes of the clonally disseminated isolates. ISKpn18-mediated disruption in the mgrB gene, which was associated with colistin resistance, was identified in two later strains, leading to the emergence of hypervirulent K. pneumoniae that was simultaneously colistin- and carbapenem-resistant. Five plasmids were recovered from each isolate, including a 178 Kb IncHI1B/FIB-type rmpA2-bearing virulence plasmid, a 177.5?Kb IncFII/R self-transferable blaKPC-2-bearing MDR plasmid, a 99.7?Kb Incl1 plasmid and two ColRNAI-type plasmids of sizes of 11.9 and 5.6?Kb, respectively. The presence of homologous regions between the non-conjugative virulence plasmid and conjugative blaKPC-2-bearing MDR plasmid suggests that transmission of the virulence plasmid from ST23 K. pneumoniae to ST11 CRKP may be mediated by the co-integrated transfer of these two plasmids. Emergence of colistin-resistant and carbapenemase-producing hypervirulent K. pneumoniae strains further emphasizes the urgency for the establishment of a coordinated global program to eradicate hypervirulent and/or pan-drug-resistant strains of K. pneumoniae from clinical settings and the community.
| S-EPMC6087712 | biostudies-literature
Project description:Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has been increasingly reported worldwide. Here, we report an outbreak caused by sequence type 859-K19 (ST859-K19) CR-hvKP isolates in a teaching hospital in China. Interestingly, K. pneumoniae ST859 was a single-locus variant of ST11 but has never been reported before. A total of 11 nonrepetitive ST859 CR-hvKP isolates were collected from 11 patients, 3 of which died of severe CR-hvKP infection. Antimicrobial susceptibility assay results showed that all the 11 CR-hvKP isolates exhibited high-level resistance to commonly used antibiotics, only remaining susceptible to colistin, tigecycline, and ceftazidime/avibactam. Whole-genome sequencing (WGS) was performed using the Illumina platform for the 11 CR-hvKP isolates, and RJ9299 was further sequenced using the PacBio platform. A phylogram tree using WGS data revealed that all the 11 CR-hvKP isolates were clustered in 1 clade, which probably indicated clone transmission. Determinants of resistance and virulence gene analysis using WGS data confirmed the 11 isolates had almost identical resistance gene profiles (blaKPC-2, blaTEM-1B, blaSHV-187, rmtB, fosA6) and virulence gene (rmpA, rmpA2, iucABCDiutA) profiles, which hint at clone spread again. The complete genome size of RJ9299 was 5,875 kb, including a 5,445-kb chromosome, a 215-kb virulence plasmid (pVir-CR-hvKP-RJ9299), a 109-kb blaKPC-2-harboring plasmid (pKPC-2-RJ9299), and three circular plasmids. Comparative genomics showed pVir-RJ9299 (IncHI1B type) and pKPC-2-RJ9299 (IncFII-IncR) possessed over 99% similarity to pLVPK and pKPC-CR-hvKP-C789, respectively. Serum resistance assays and a Galleria mellonella infection model showed the 11 isolates exhibited different levels of virulence. This is the first report of an outbreak caused by ST859 CR-hvKP isolates. IMPORTANCE The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) in China has posed a great threat to public health, especially in the highly transmissible ST11 clone. With the transmission of virulence and resistance determinants, CR-hvKP isolates have been reported in an increasing number of sequence types (STs), including ST23, ST65, ST1797, ST43, ST231, ST147, ST15, ST383, ST268, ST595, ST375, ST48, and ST307. Here, we report an outbreak caused by ST859-K19 CR-hvKP isolates in a teaching hospital in China. ST859 is a single-locus variant of ST11. There is no literature on ST859 K. pneumoniae in public databases, let alone ST859 CR-hvKP isolates. To our knowledge, this is the first report to depict the molecular and genomic characteristics of ST859 CR-hvKP isolates. Active surveillance approaches should be implemented to promptly find the spread of CR-hvKP isolates in health care settings.
| S-EPMC9239081 | biostudies-literature