Two ST11 Klebsiella pneumoniae strains exacerbate colorectal tumorigenesis in a colitis-associated mouse model.
Ontology highlight
ABSTRACT:
SUBMITTER: Chiang MK
PROVIDER: S-EPMC8496539 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
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 and hypervirulent K. pneumoniae (CR-HvKP) strains that have emerged recently have caused infections of extremely high mortality in various countries. In this study, we discovered a conjugative plasmid that encodes carbapenem resistance and hypervirulence in a clinical ST86 K2 CR-HvKP, namely 17ZR-91. The conjugative plasmid (p17ZR-91-Vir-KPC) was formed by fusion of a non-conjugative pLVPK-like plasmid and a conjugative blaKPC-2-bearing plasmid and is present dynamically with two other non-fusion plasmids. Conjugation of p17ZR-91-Vir-KPC to other K. pneumoniae enabled them to rapidly express the carbapenem resistance and hypervirulence phenotypes. More importantly, genome analysis provided direct evidence that p17ZR-91-Vir-KPC could be directly transmitted from K2 CR-HvKP strain, 17ZR-91, to ST11 clinical K. pneumoniae strains to convert them into ST11 CR-HvKP strains, which explains the evolutionary mechanisms of recently emerged ST11 CR-HvKP strains.
| S-EPMC8169677 | biostudies-literature
Project description:Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major severe threat for human health, and its spread is largely driven by a few dominant lineages defined by sequence types (ST) and capsular (KL) types. ST11-KL64 is one such dominant lineage that is particularly common in China but also has a worldwide distribution. However, the population structure and origin of ST11-KL64 K. pneumoniae remain to be determined. We retrieved all K. pneumoniae genomes (n = 13,625, as of June 2022) from NCBI, comprising 730 ST11-KL64 strains. Phylogenomic analysis of core-genome single-nucleotide polymorphisms identified two major clades (I and II) plus an additional singleton of ST11-KL64. We performed dated ancestral reconstruction analysis using BactDating and found that clade I likely emerged in 1989 in Brazil, while clade II emerged around 2008 in eastern China. We then investigated the origin of the two clades and the singleton using a phylogenomic approach combined with analysis of potential recombination regions. We found that ST11-KL64 clade I is likely a hybrid with 91.2% (ca. 4.98 Mb) of the chromosome derived from the ST11-KL15 lineage and 8.8% (483 kb) acquired from ST147-KL64. In contrast, ST11-KL64 clade II was derived from ST11-KL47 with swapping of a 157-kb region (3% of the chromosome) containing the capsule gene cluster with clonal complex 1764 (CC1764)-KL64. The singleton also evolved from ST11-KL47 but with swapping of a 126-kb region with ST11-KL64 clade I. In conclusion, ST11-KL64 is a heterogenous lineage comprising two major clades and a singleton with different origins that emerged in different countries at different time points. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a severe threat globally and is associated with increased lengths of hospital stay and high mortality in affected patients. The spread of CRKP is largely driven by a few dominant lineages, including ST11-KL64, the dominant type in China with a worldwide distribution. Here, we tested the hypothesis that ST11-KL64 K. pneumoniae is a single genomic lineage by performing a genome-based study. However, we found that ST11-KL64 comprises a singleton and two major clades, which emerged in different countries in different years. In particular, the two clades and the singleton have different origins and acquired the KL64 capsule gene cluster from various sources. Our study underscores that the chromosomal region containing the capsule gene cluster is a hot spot of recombination in K. pneumoniae. This represents a major evolutionary mechanism employed by some bacteria for rapid evolution with novel clades that accommodate stress for survival.
| S-EPMC10101065 | biostudies-literature
Project description:Carbapenem-resistant ST11_KL64 Klebsiella pneumoniae emerged as a significant public health concern in Taiwan, peaking between 2013 and 2015, with the majority of isolates exhibiting OXA-48 as the sole carbapenemase. In this study, we employed whole-genome sequencing to investigate the molecular underpinnings of ST11_KL64 isolates collected from 2013 to 2021. Phylogenomic analysis revealed a notable genetic divergence between the ST11_KL64 strains in Taiwan and those in China, suggesting an independent evolutionary trajectory. Our findings indicated that the ST11_KL64_Taiwan lineage originated from the ST11_KL64 lineage in Brazil, with recombination events leading to the integration of ICEKp11 and a 27-kb fragment at the tRNAASN sites, shaping its unique genomic landscape. To further elucidate this unique sublineage, we examined the plasmid contents. In contrast to ST11_KL64_Brazil strains, which predominantly carried blaKPC-2, ST11_KL64_Taiwan strains exhibited the acquisition of an epidemic blaOXA-48-carrying IncL plasmid. Additionally, ST11_KL64_Taiwan strains consistently harbored a multi-drug resistance IncC plasmid, along with a collection of gene clusters that conferred resistance to heavy metals and the phage shock protein system via various Inc-type plasmids. Although few, there were still rare ST11_KL64_Taiwan strains that have evolved into hypervirulent CRKP through the horizontal acquisition of pLVPK variants. Comprehensive characterization of the high-risk ST11_KL64 lineage in Taiwan not only sheds light on its epidemic success but also provides essential data for ongoing surveillance efforts aimed at tracking the spread and evolution of ST11_KL64 across different geographical regions. Understanding the molecular underpinnings of CRKP evolution is crucial for developing effective strategies to combat its emergence and dissemination.
| S-EPMC10748404 | biostudies-literature
Project description:Multidrug-resistant Klebsiella pneumoniae and hypervirulent K. pneumoniae (hvKP) have traditionally been considered two individual populations; however, strains displaying both phenotypes have emerged during the recent decade. Understanding the genotypic and phenotypic basis of the convergence could be of clinical importance. In this study, we aimed to evaluate the pathogenicity associated with different combinations of genotypes (i.e., sequence types, virulence factors, and capsular serotypes) and phenotypes (i.e., hypermucoviscosity and drug susceptibility) in K. pneumoniae. A total of 11 K. pneumoniae isolates causing bloodstream infections were included in the study, and they were assigned to seven STs (ST23, ST15, ST268, ST660, ST86, ST65, and ST1660) and carried various K-loci (KL1, KL2, KL16, KL20, and KL24). Hypermucoviscosity was observed for six isolates. bla KPC-2 was detected in six carbapenem-resistant isolates, and the remaining ones were either multidrug-resistant or resistant to two types of antibiotics. Aerobactin- and yersiniabactin-encoding genes were detected in all isolates. Although rmpA2 was detected in all isolates, most contained frameshift mutations (82%). Genes encoding salmochelin, RmpA, and PEG344 were detected in seven isolates. Colibactin-encoding genes were carried by six isolates. Discrepancies among measured virulence in Galleria mellonella and the serum-killing assay, and genotypes and phenotypes were detected. The results illustrate the complexity and difficulty with the current knowledge of hypervirulence to predict the phenotype by using genetic and phenotypic markers. Additionally, the emergence of carbapenem resistance in two isolates of KPC-2-producing hvKP of different sequence types emphasizes the urgency with which reliable clinical diagnostics for hvKP is needed.
| S-EPMC7314899 | biostudies-literature
Project description:Background: Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) poses distinct clinical challenges due to extensively drug resistant (XDR) phenotype, and sequence type (ST) 11 is the most dominant blaKPC-2-bearing CP-Kp clone in China. The purpose of this current retrospective study was to explore the genetic factors associated with the success of XDR CP-Kp ST11 strains circulated in the intensive care unit (ICU) of a Chinese tertiary hospital.Methods: Six ST11 XDR CP-Kp strains were identified between May and December 2014 and validated by minimum inhibitory concentration examination, polymerase chain reaction, and pyrosequencing. The six ST11 XDR CP-Kp, as well as three multi-drug resistant (MDR) and four susceptible strains, were sequenced using single-molecule real-time method. Comprehensively structural and functional analysis based on comparative genomics was performed to identify genomic characteristics of the XDR ST11 CP-Kp strains.Results: We found that ST11 XDR blaKPC-2-bearing CP-Kp strains isolated from inpatients spread in the ICU of the hospital. Functionally, genes associated with information storage and processing of the ST11 XDR CP-Kp strains were more abundant than those of MDR and susceptible strains, especially genes correlative with mobile genetic elements (MGEs) such as transposons and prophages. Structurally, eleven large-scale genetic regions taken for the unique genome in these ST11 XDR CP-Kp strains were identified as MGEs including transposons, integrons, prophages, genomic islands, and integrative and conjugative elements. Three of them were located on plasmids and eight on chromosomes; five of them were with antimicrobial resistance genes and eight with adaptation associated genes. Notably, a new blaKPC-2-bearing ??Tn1721-blaKPC-2 transposon, probably transposed and truncated from ?Tn1721-blaKPC-2 by IS903D and ISKpn8, was identified in all six ST11 XDR CP-Kp strains.Conclusion: Our findings suggested that together with clonal spread, MGEs identified uniquely in the ST11 XDR CP-Kp strains might contribute to their formidable adaptability, which facilitated their widespread dissemination in hospital.
| S-EPMC7722564 | biostudies-literature
Project description:A novel Klebsiella pneumoniae carbapenemase (KPC) variant, KPC-93, was identified in two Klebsiella pneumoniae clinical isolates from a patient from China treated with ceftazidime-avibactam. KPC-93 possessed a five-amino-acids insertion (Pro-Asn-Asn-Arg-Ala) between Ambler positions 267 and 268 in KPC-2. Cloning and expression of the blaKPC-93 gene in Escherichia coli, followed by determination of minimum inhibitory concentration (MIC) values and kinetic parameters, showed that KPC-93 exhibited increased resistance to ceftazidime-avibactam, but a drastic decrease in carbapenemase activity. Our data highlight that a KPC variant conferring resistance to ceftazidime-avibactam could be easily induced by ceftazidime-avibactam treatment and that actions are required to control dissemination of these determinants. IMPORTANCE Ceftazidime-avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor combination with activity against serine β-lactamases, including the Ambler class A enzyme KPC. However, during recent years, there have been increasing reports of emergence of new KPC variants that could confer resistance to CZA. This has limited its clinical application. Here, we reported a new KPC variant, KPC-93, that could confer CZA resistance. KPC-93 possessed a five-amino-acids insertion (Pro-Asn-Asn-Arg-Ala) between Ambler positions 267 and 268 in KPC-2. Our findings have revealed the potential risk of blaKPC gene mutations associated with CZA exposure over a short period of time.
| S-EPMC9045388 | biostudies-literature
Project description:The bacterial pathogen Klebsiella pneumoniae causes urinary tract infections in immunocompromised patients. Generally, the overuse of antibiotics contributes to the potential development and the spread of antibiotic resistance. In fact, certain strains of K. pneumoniae are becoming increasingly resistant to antibiotics, making infection by these strains more difficult to treat. The use of bacteriophages to control pathogens may offer a non-antibiotic-based approach to treat multidrug-resistant (MDR) infections. However, a detailed understanding of phage-host interactions is crucial in order to explore the potential success of phage-therapy for treatment. In this study, we investigated the molecular epidemiology of nine carbapenemase-producing K. pneumoniae isolates from a local hospital in Shanghai, China. All strain isolates belong to sequence type 11 (ST11) and harbor the blaKPC-2 gene. The S1-PFGE (S1 nuclease pulsed field gel electrophoresis) pattern of the isolates did not show any relationship to the multilocus sequence typing (MLST) profiles. In addition, we characterized phage 117 and phage 31 and assessed the potential application of phage therapy in treating K. pneumoniae infections in vitro. The results of morphological and genomic analyses suggested that both phages are affiliated to the T7 virus genus of the Podoviridae family. We also explored phage-host interactions during growth in both planktonic cells and biofilms. The phages' heterogeneous lytic capacities against K. pneumoniae strains were demonstrated experimentally. Subsequent culture and urine experiments with phage 117 and host Kp36 initially demonstrated a strong lytic activity of the phages. However, rapid regrowth was observed following the initial lysis which suggests that phage resistant mutants were selected in the host populations. Additionally, a phage cocktail (117 + 31) was prepared and investigated for antimicrobial activity. In Luria Broth (LB) cultures, we observed that the cocktail showed significantly higher antimicrobial activity than phage 117 alone, but this was not observed in urine samples. Together, the results demonstrate the potential therapeutic value of phages in treating K. pneumoniae urinary tract infections.
| S-EPMC6893751 | biostudies-literature
Project description:In this study, we investigate the characteristics of two main clones of carbapenemase-producing Klebsiella pneumoniae isolates from South Korea, ST11 and ST307, including carbapenem-susceptible isolates. Antibiotic susceptibility, serotype or wzi allelic type, the presence of virulence genes, and virulence with respect to serum resistance and macrophage internalization were determined for ST11 and ST307 isolates. ST11 isolates had a wide range of characteristics, including serotype and virulence, compared with those of homogeneous ST307 isolates. The wzi14 or K14 type had higher virulence than that of other serotypes among the ST11 isolates, and the homogeneous ST307 isolates showed similar virulence level as that of the wzi14-type ST11 isolates. Our data suggest that it is necessary to monitor not only the introduction and spread of a specific clone, but also its detailed serotype.
| S-EPMC9504348 | biostudies-literature
Project description:ObjectivesST11 KPC-producing Klebsiella pneumoniae (Kp) is highly prevalent in China. We investigated the inter- and intra- host transmission and evolution characteristics of ST11 KPC-producing Kp.MethodsA retrospective study was conducted in a hospital. The clinical data and antimicrobial resistance (AMR) phenotypes were collected. Whole genome sequencing was performed. The transmission route was reconstructed by combining single nucleotide polymorphisms (SNPs) with the clinical information. Hypervirulent Kp (HvKp) was defined as the presence of some combination of peg-344, iroB, iucA, rmpA, or rmpA2.ResultsFifty-eight Kp strains isolated from thirty-five patients were enrolled. The information of one isolate was missing. The mean age of the patients was 74.3 ± 18.0 years, and 18 (50.0%) were female. Fifteen patients (41.7%, 15/36) presented with poor prognosis. All the strains were identified as ST11, and 57 strains harbored blaKPC-2. Two distinguished clades were identified based on the 1,325 high quality SNPs. In clade 1, carbapenem-resistant (CR)-hvKp accounted for 48.3% of the strains (28/58), which mostly presented as KL64 subclones, whereas CR-classical Klebsiella pneumoniae (cKp) commonly possessing KL47 were clustered in Clade 2. One CR-hvKp strain might have originated from the CR-cKp strain from within-host evolution. Even worse, a prolonged transmission of CR-hvKp has led to its spread into healthcare institutes.ConclusionTwo endemic subclones of ST11 KPC-producing Kp, KL64-CR-hvKp and KL47-CR-cKp, were transmitted in parallel within the hospital and/or the healthcare institute, suggesting that the ongoing genomic surveillance should be enhanced.
| S-EPMC9540996 | biostudies-literature