Dataset Information

In silico characterization of bla _NDM-harboring plasmids in Klebsiella pneumoniae.

ABSTRACT: Klebsiella pneumoniae is a primary culprit of antibiotic-resistant nosocomial infections worldwide, and infections caused by NDM-producing strains are a major threat due to limited therapeutic options. The majority of bla _NDM cases occur on plasmids; therefore, we explored the relationships between plasmids and bla _NDM genes in K. pneumoniae by analyzing the variants of bla _NDM, replicon types, conjugative transfer regions of 171 bla _NDM-harboring plasmids from 4,451 K. pneumoniae plasmids. Of the nine identified bla _NDM variants, bla _NDM-1 (73.68%) and bla _NDM-5 (16.37%) were the most dominant. Over half of the bla _NDM-harboring plasmids of K. pneumoniae were classified into IncF plasmids. IncX3 single-replicon plasmids (46-57 kb) carried genes encoding relaxases of the MOB_P family, T4CP genes of the VirD4/TraG subfamily, and VirB-like T4SS gene clusters, which were mainly geographically distributed in China. We found 10 bla _NDM-harboring IncN plasmids (38.38-63.05 kb) carrying the NW-type origin of transfer (oriT) regions, genes coding for relaxases of MOB_F family, genes encoding T4CPs of the TrwB/TraD subfamily, and Trw-like T4SS gene clusters, which were also mainly geographically distributed in China. Moreover, we identified 21 IncC plasmids carrying bla _NDM-1 (140.1-329.2 kb), containing the A/C-type oriTs, genes encoding relaxases of MOB_H family, genes encoding T4CPs belonging to TrwB/TraD subfamily, and Tra_F-like T4SS gene clusters. The bla _NDM-harboring IncC plasmids were widely geographically distributed all over the world, mainly in the United States, China and Viet Nam. These findings enhance our understanding of the diversity of bla _NDM-harboring plasmids in K. pneumoniae.

SUBMITTER: Zeng Z

PROVIDER: S-EPMC9727287 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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In silico characterization of bla NDM-harboring plasmids in Klebsiella pneumoniae.

Zeng Zhu Z Lei Lei L Li Linman L Hua Shengni S Li Wenting W Zhang Limei L Lin Qiuping Q Zheng Zhixiong Z Yang Jing J Dou Xiaohui X Li Luan L Li Xiaobin X

Frontiers in microbiology 20221123

Klebsiella pneumoniae is a primary culprit of antibiotic-resistant nosocomial infections worldwide, and infections caused by NDM-producing strains are a major threat due to limited therapeutic options. The majority of bla NDM cases occur on plasmids; therefore, we explored the relationships between plasmids and bla NDM genes in K. pneumoniae by analyzing the variants of bla NDM, replicon types, conjugative transfer regions of 17 ...[more]

PMID: 36504778

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Project description:Carbapenem-resistant Klebsiella pneumoniae (CRKP), which harbors the bla NDM plasmid, has been reported extensively and is considered a global threat clinically. However, characterization and comparisons of bla NDM-1-carrying and bla NDM-5-harboring IncX3-type plasmids in CRKP are lacking. Here, we systematically compared the differences in the characteristics, genetic backgrounds, transferability, and fitness costs between bla NDM-1-carrying and bla NDM-5-carrying plasmids in K. pneumoniae isolates. Fifteen NDM-producing CRKP isolates were recovered from 1376 CRKP isolates between 2019 and 2021, of which 4 were positive for bla NDM-1 and 11 were positive for bla NDM-5. All strains were highly resistant to carbapenem but remained susceptible to tigecycline and colistin. Core-genome-based phylogenetic analyses revealed that these strains were not clonally related. Whole-genome sequencing showed that bla NDM-1 and bla NDM-5 were located on ~54 kb and ~46 kb IncX3-type plasmids, respectively. The backbone, genetic context, and fitness cost of the bla NDM-1-bearing plasmid were highly similar to those of the bla NDM-5-carrying plasmid, but the transferability of the bla NDM-1-positive plasmid was greater than that of the bla NDM-5-positive plasmid. In conclusion, the transmission of bla NDM-1 or bla NDM-5 is mainly disseminated by plasmids rather than clonal spread. The high transfer frequency of the IncX3 plasmid facilitates the prevalence and dissemination of NDM-KP among Enterobacteriaceae. IMPORTANCE The emergence of NDM-producing Klebsiella pneumoniae is a severe challenge to public health. The widespread presence of bla NDM-1 and bla NDM-5 in Enterobacteriaceae has aroused broad concern. In this study, we performed molecular characterization of bla NDM-1-carrying and bla NDM-5-harboring IncX3-type plasmids in carbapenem-resistant Klebsiella pneumoniae (CRKP) and compared their phenotypes between strains with different bla NDM subtype. Our findings highlight the importance of IncX3-type plasmids in the transfer of the bla NDM-1 and bla NDM-5 genes and demonstrate that the bla NDM-1 plasmid possesses higher transfer ability. These data will provide important insights into carbapenem resistance gene transfer via plasmids and their further spread in clinical settings.

Project description:New Delhi metallo-β-lactamase (NDM)-producing clinical strains in Acinetobacter spp. have been recently reported in many countries and have received considerable attention. The vast majority of blaNDM cases occur on conjugative plasmids, which play a vital role in disseminating blaNDM. To characterize the conjugative plasmids bearing blaNDM genes in Acinetobacter spp., we analyzed the variants of blaNDM, conjugative transfer regions, genetic contexts of blaNDM, and the phylogenetic pattern of the 62 predicted blaNDM-positive plasmids, which were selected from 1,191 plasmids of Acinetobacter species from GenBank. We identified 30 conjugative plasmids from the 62 blaNDM-harboring plasmids in Acinetobacter species, with the oriT sites similar to plasmid pNDM-YR7 in our study, genes coding for relaxases of the MOBQ family, genes encoding type IV coupling proteins (T4CPs) of the TrwB/TraD subfamily, and VirB-like type IV secretion system (T4SS) gene clusters. The genome sizes of all 30 pNDM-YR7-like plasmids ranged from 39.36 kb to 49.65 kb, with a median size of 44.56 kb. The most common species of Acinetobacter containing the blaNDM-positive conjugative plasmids was A. baumannii, followed by Acinetobacter lwoffii and Acinetobacter indicus. Notably, pNDM-YR7 is the first report on a blaNDM-positive conjugative plasmid in Acinetobacter junii. Moreover, all 30 blaNDM-positive conjugative plasmids in Acinetobacter species were found to contain genetic contexts with the structure ISAba14-aph(3')-VI-ISAba125-blaNDM-ble. Our findings provide important insights into the phylogeny and evolution of blaNDM-positive plasmids of Acinetobacter species and further address their role in acquiring and spreading blaNDM genes in Acinetobacter species. IMPORTANCE Conjugative plasmids harboring the blaNDM gene play a vital role in disseminating carbapenem resistance. In this study, we first report a conjugative plasmid, pNDM-YR7, in Acinetobacter junii. Based on the genomic characteristics of the blaNDM-positive pNDM-YR7, we performed in silico typing and comparative analysis of blaNDM-positive plasmids using the 1,191 plasmids of Acinetobacter species available in the NCBI RefSeq database. We analyzed the characteristics of blaNDM-positive plasmids, including the variants of blaNDM, genetic features associated with blaNDM, conjugative transfer regions, and the phylogenetic pattern of the blaNDM-positive plasmids. All 30 blaNDM-positive conjugative plasmids were found to contain an ISAba14-aph(3')-VI-ISAba125-blaNDM-ble region. This study provides novel insights into the phylogeny and evolution of blaNDM-harboring conjugative plasmids and contributes to the repertoire of knowledge surrounding blaNDM-positive plasmids in the genus Acinetobacter.

Project description:The emergence and spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a serious medical problem worldwide. Acquired OXA-48-like carbapenemases encoded by plasmids are important causes of carbapenem resistance in K. pneumoniae. To explore the links between plasmids and bla OXA-48-like genes in K. pneumoniae, we systematically analyzed the variants of bla OXA-48-like plasmid replicon types, phylogenetic patterns, geographic distribution, conjugative transfer regions, and the genetic environments surrounding bla OXA-48-like of 191 bla OXA-48-like-harboring plasmids, which were identified from 4451 plasmids of K. pneumoniae downloaded from GenBank. Our results showed that seven different variants of bla OXA-48-like genes were identified from the 191 bla OXA-48-like-harboring plasmids in K. pneumoniae, with bla OXA-48, bla OXA-232, and bla OXA-181 being highly prevalent. In K. pneumoniae, bla OXA-48 was mainly carried by the composite transposon Tn1999.2 located on IncL/M-type conjugative plasmids, which were mainly geographically distributed in Switzerland, Germany, and China. In K. pneumoniae, the blaOXA-232 gene was mainly carried by 6.1-kb ColKP3-type mobilizable plasmids, which were mainly isolated in India. In K. pneumoniae, bla OXA-181 was mainly carried by a group of 50-kb ColKP3-IncX3 hybrid conjugative plasmids and a group of small ColKP3-type mobilizable plasmids with lengths of 5.9-9.3 kb, the former was sporadically discovered in China, South Korea, India, and Czech Republic, while the latter was almost all isolated in India. In addition, five bla OXA-245-harboring 65.9-kb IncL plasmids of K. pneumoniae isolated in Spain were found to have the genetic context of bla OXA-245 more complicated than that of bla OXA-48-harboring IncL/M-type plasmids, with two copies of IS1R inserted both upstream and downstream of bla OXA-245-lysR. These findings enhance our understanding of the genetic diversity of bla OXA-48-like-harboring plasmids in K. pneumoniae.

Project description:Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global public health threat, and CRKP strains carrying blaNDM plasmids are of particular concern. Here, the antimicrobial resistance and molecular epidemiological characteristics of 59 CRKP strains isolated from patients receiving care at a tertiary hospital in China from 2019 to 2021 were determined through antimicrobial resistance testing and genomic sequence analysis. We analyzed the genetic characteristics and transmissibility of blaNDM-harboring plasmids through S1-digested pulsed field gel electrophoresis, Southern blotting, and conjugation assays. The virulence levels of the strains were evaluated using a Galleria mellonella larvae infection model. All the CRKP strains were multidrug resistant, but none were resistant to colistin or tigecycline. A total of eight sequence types (STs) were detected in these CRKPs, with ST11 (39/59) and ST15 (12/59) being the most common. Among the carbapenemase genes, blaKPC (39/59) and blaNDM (18/59) were the most common, with blaKPC-2 transmitted mainly through ST11 clones and blaNDM-5 transmitted through ST15 clones. The blaNDM-harboring plasmids primarily belong to the incompatibility type IncX3 (14/18). IS26-mediated gene recombination, sequence insertion, and plasmid integration were observed to occur during the dissemination process. The resistance gene profile mediated by blaNDM-harboring plasmids can be transferred through conjugation, which have almost no fitness cost and is extremely stable after passage. Six of these strains presented carbapenem resistance combined with hypervirulence (CR-hvKP), including ST23-KL1, ST218-KL57, ST17-KL112, and ST147-KL64. Additionally, blaNDM-harboring plasmids can disseminate rapidly over large surface areas and persist for a long time in medical institutions, leading to outbreaks of highly resistant clones associated with CR-hvKP.IMPORTANCEThe appearance of plasmids carrying blaNDM and the rise of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have significantly escalated the public health risk associated with Carbapenem-resistant Klebsiella pneumoniae (CRKP). In this study, we described the resistance rates, virulence factors, and molecular epidemiology of 59 CRKP isolated from patients at a tertiary hospital in China from 2019 to 2021. Beyond this, we also assessed the characteristics of blaNDM-harboring plasmids and their dissemination patterns among CRKP, especially some CR-hvKP. Our research contributes to the field of blaNDM dissemination studies, prompting researchers to formulate strict measures to prevent and control the development of blaNDM-harboring plasmids, which is instrumental in the clinical development of targeted treatment plans.

Dataset Information

In silico characterization of bla _NDM-harboring plasmids in Klebsiella pneumoniae.

Publications

<i>In silico</i> characterization of <i>bla</i> <sub>NDM</sub>-harboring plasmids in <i>Klebsiella pneumoniae</i>.

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