Dataset Information

Emergence of a Multidrug-Resistant Hypervirulent Klebsiella pneumoniae Sequence Type 23 Strain with a Rare bla CTX-M-24-Harboring Virulence Plasmid.

ABSTRACT: Here, we report a multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-HvKP) strain of sequence type 23 (ST23) with a rare hybrid plasmid harboring virulence genes and bla CTX-M-24, and we analyze the genetic basis for relationship between genotypes and MDR-hypervirulence phenotypes. Further analysis indicates that the hybrid plasmid is formed by IS903D-mediated intermolecular transposition of the bla CTX-M-24 gene into the virulence plasmid. The emergence of MDR-HvKP strains, especially those carrying drug-resistant virulent plasmids, poses unprecedented threats/challenges to public health. This is a dangerous trend and should be closely monitored.

SUBMITTER: Shen D

PROVIDER: S-EPMC6395898 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Emergence of a Multidrug-Resistant Hypervirulent Klebsiella pneumoniae Sequence Type 23 Strain with a Rare blaCTX-M-24-Harboring Virulence Plasmid.

Shen Dingxia D Ma Guannan G Li Cuidan C Jia Xinmiao X Qin Chuan C Yang Tingting T Wang Lifeng L Jiang Xiaoyuan X Ding Nan N Zhang Xiuli X Yue Liya L Yin Zhe Z Zeng Lijun L Zhao Yongliang Y Zhou Dongsheng D Chen Fei F

Antimicrobial agents and chemotherapy 20190226 3

Here, we report a multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-HvKP) strain of sequence type 23 (ST23) with a rare hybrid plasmid harboring virulence genes and blaCTX-M-24, and we analyze the genetic basis for relationship between genotypes and MDR-hypervirulence phenotypes. Further analysis indicates that the hybrid plasmid is formed by IS903D-mediated intermolecular transposition of the blaCTX-M-24 gene into the virulence plasmi ...[more]

PMID: 30602516

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Project description:Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKp) has been emerging worldwide. However, the clinical, microbiological, and genomic characteristics of newly emerged MDR sequence type 65 (ST65) hvKp are unclear. We conducted active longitudinal genomic surveillance of K. pneumoniae in the hospital starting in 2017. Clinical characteristics, including demographic data, infection type, and outcomes, were collected. Whole-genome sequencing was performed to clarify phylogenetic and plasmid features, and phenotype determined by growth curves, plasmid transferability and stability, hypermucoviscosity, biofilm formation, and serum survival were analyzed to microbiologically characterize ST65 in depth. Ten ST65 (1.4%, 10/720) isolates were detected from 720 K. pneumoniae isolates in total. Nine patients (90%, 9/10) were older than 60 years and had multiple underlying diseases. All ST65 K. pneumoniae isolates harbored iucA, rmpA, rmpA2, iroB, and peg344 and were identified as hvKp. Surprisingly, two MDR-hvKp isolates that grew slowly were observed. Isolate PEKP4222 harbored a pLVPK-like plasmid and a conjunctive MDR plasmid. Isolate P1 harbored blaKPC-3 in a new plasmid, pP1-54, resulting in an extensively drug-resistant (XDR) phenotype; this isolate, which might have evolved from a strain harboring blaKPC-2, resulted in fatal infection. The pP1-54 plasmid could not be transferred to Escherichia coli by conjugation but could be stably inherited vertically. Interestingly, P1 also carried the pLVPK-like plasmid and acquired various antimicrobial resistance genes, and blaCTX-M-3 was detected in the IncB/O/K/Z plasmid. The convergence of XDR and hypervirulence within classical ST65 hvKp is emerging, highlighting the need for enhanced genomic surveillance. IMPORTANCE XDR-hvKp poses a great challenge to public health. ST65, a classical hvKp subtype, mostly presented with hypermucoviscosity, which restricts antimicrobial resistance acquisition. However, few studies have demonstrated the clinical, microbiological, and genomic characteristics of ST65, especially MDR-ST65 hvKp. Here, we first reported that ST65 hvKp acquired blaKPC-3 and then conferred the XDR-hvKp phenotype. Genomic context analysis concluded that the blaKPC-3 gene might have evolved from blaKPC-2. Additionally, the pLVPK-like plasmid seemed to acquire more resistance genes, and blaCTX-M-3 located in the IncB/O/K/Z plasmid was observed. The XDR-hvKp phenotype could be stably inherited vertically, indicating that strains harboring blaKPC-3 and pLVPK-like plasmids could persistently exist in hospital settings. These data suggest that genomic adaptation is rapid and that enhanced surveillance is essential.

Project description:The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates in Egyptian hospitals has been reported. However, the genetic basis and analysis of the plasmids associated with carbapenem-resistant hypervirulent K. pneumoniae (CR-HvKP) in Egypt have not been presented. Therefore, we attempted to decipher the plasmid sequences that are responsible for transferring the determinants of carbapenem resistance, particularly bla NDM-1 and bla KPC-2 Out of 34 K. pneumoniae isolates collected from two tertiary hospitals in Egypt, 31 were CRKP. Whole-genome sequencing revealed that our isolates were related to 13 different sequence types (STs). The most prevalent ST was ST101, followed by ST383 and ST11. Among the CRKP isolates, one isolate named EBSI036 has been reassessed by Nanopore sequencing. Genetic environment analysis showed that EBSI036 carried 20 antibiotic resistance genes and was identified as a CR-HvKP strain: it harbored four plasmids, namely, pEBSI036-1-NDM-VIR, pEBSI036-2-KPC, pEBSI036-3, and pEBSI036-4. The two carbapenemase genes bla NDM-1 and bla KPC-2 were located on plasmids pEBSI036-1-NDM-VIR and pEBSI036-2-KPC, respectively. The IncFIB:IncHI1B hybrid plasmid pEBSI036-1-NDM-VIR also carried some virulence factors, including the regulator of the mucoid phenotype (rmpA), the regulator of mucoid phenotype 2 (rmpA2), and aerobactin (iucABCD and iutA). Thus, we set out in this study to analyze in depth the genetic basis of the pEBSI036-1-NDM-VIR and pEBSI036-2-KPC plasmids. We report a high-risk clone ST11 KL47 serotype of a CR-HvKP strain isolated from the blood of a 60-year-old hospitalized female patient from the intensive care unit (ICU) in a tertiary care hospital in Egypt, which showed the cohabitation of a novel hybrid plasmid coharboring the bla NDM-1 and virulence genes and a bla KPC-2-carrying plasmid.IMPORTANCE CRKP has been registered in the critical priority tier by the World Health Organization and has become a significant menace to public health. The emergence of CR-HvKP is of great concern in terms of both disease and treatment. In-depth analysis of the carbapenemase-encoding and virulence plasmids may provide insight into ongoing recombination and evolution of virulence and multidrug resistance in K. pneumoniae Thus, this study serves to alert contagious disease clinicians to the presence of hypervirulence in CRKP isolates in Egyptian hospitals.

Project description:Since the discovery of blaNDM-1, NDM β-lactamases have become one of the most widespread carbapenemases worldwide. To date, 43 different NDM variants have been reported but some, such as blaNDM-23, have not been characterized in detail yet. Here, we describe the emergence of a novel blaNDM-23 allele from a blaNDM-1 ancestor and the multidrug resistance plasmid that has disseminated it through a Klebsiella pneumoniae ST437 clone in several Spanish hospitals. Between 2016 and 2019, 1,972 isolates were collected in an epidemiological survey for extended-spectrum-β-lactamase (ESBL)-producing Klebsiella pneumoniae in the Comunitat Valenciana (Spain). Three carbapenem-resistant strains failed to be detected by carbapenemase-producing Enterobacteriaceae (CPE) screening tests. These isolates carried a blaNDM-23 gene. To characterize this gene, its emergence, and its dissemination, we performed antimicrobial susceptibility tests, hybrid sequencing with Illumina and Nanopore technologies, and phylogenetic analyses. The MICs of the blaNDM-23 allele were identical to those of the blaNDM-1 allele. The blaNDM-23 allele was found in 14 isolates on a 97-kb nonmobilizable, multidrug-resistant plasmid carrying 19 resistance genes for 9 different antimicrobial families. In this plasmid, the blaNDM-23 gene is in the variable region of a complex class 1 integron with a singular genetic environment. The small genetic distance between blaNDM-23-producing isolates reflects a 5-year-long clonal dispersion involving several hospitals and interregional spread. We have characterized the genomic and epidemiological contexts in the emergence and community spread of a new blaNDM-23 allele in a multidrug resistance (MDR) plasmid of Klebsiella pneumoniae. IMPORTANCE At a time when antimicrobial resistance has become one of the biggest concerns worldwide, the emergence of novel alleles and extremely drug-resistant plasmids is a threat to public health worldwide, especially when they produce carbapenem resistance in one of the most problematic pathogens, such as Klebsiella pneumoniae. We used genomic epidemiology to describe the emergence of a novel NDM-23 allele and identify it in a MDR plasmid that has disseminated through a K. pneumoniae ST437 clone in several hospitals in Spain. Using bioinformatic and phylogenetic analyses, we have traced the evolutionary and epidemiological route of the new allele, the hosting plasmid, and the strain that carried both of them from Pakistan to Spain. A better understanding of the NDM-producing K. pneumoniae populations and plasmids has made evident the spread of this clone through the region, enhancing the importance of genomic surveillance in the control of antimicrobial resistance.

Project description:Although the prevalence of carbapenem-resistant Enterobacterales remains low in Japan, these bacteria are a growing problem worldwide, owing to their multidrug resistance phenotype. We isolated a multidrug-resistant Providencia rettgeri strain, NR1418, harboring a rare blaIMP variant, blaIMP-70, a novel blaCTX-M variant, designated blaCTX-M-253, and blaMOX-1. This strain is resistant to β-lactams, amikacin, levofloxacin, and colistin. Genomic analysis revealed that NR1418 carries two plasmids, designated pNR1418-1 and pNR1418-2. The pNR1418-1 plasmid harbors blaCTX-M-253, blaTEM-1, and blaMOX-1, while the pNR1418-2 plasmid harbors blaIMP-70, which is located in a class 1 integron. Both plasmids exhibit high similarities with the plasmid of the P. rettgeri isolate BML2526, which also harbors blaIMP-70 and was identified in the same region of Japan as NR1418 at a different point in time. This indicates the possibility of the emergence and evolution of IMP-70-producing P. rettgeri and suggests that the plasmid of BML2526 may have occurred following recombination of the two plasmids harbored by NR1418. Further, blaIMP-70 and blaCTX-M-253 were found on unique plasmids, indicating that they likely evolved through mutations and recombination. IMPORTANCE Although Providencia rettgeri is an opportunistic pathogen, its intrinsic resistance to colistin and tigecycline makes the treatment of carbapenem-resistant P. rettgeri challenging. We isolated a multidrug-resistant P. rettgeri strain which harbored a rare blaIMP variant, blaIMP-70, a novel blaCTX-M variant, blaCTX-M-253, and blaMOX-1 from a urinary sample obtained in Osaka, Japan. We investigated its genetic structure and evaluated the evolution of the plasmids carrying these genes. We show that blaIMP-70, blaCTX-M-253, and blaMOX-1 are present on unique plasmids and that they have high similarities to the plasmid of another IMP-70-producing P. rettgeri isolate that was identified as being from the same location. The evolution of plasmids through mutations and recombination may play a role in the development and spread of multidrug resistance.

Dataset Information

Emergence of a Multidrug-Resistant Hypervirulent Klebsiella pneumoniae Sequence Type 23 Strain with a Rare bla CTX-M-24-Harboring Virulence Plasmid.

Publications

Emergence of a Multidrug-Resistant Hypervirulent Klebsiella pneumoniae Sequence Type 23 Strain with a Rare <i>bla</i><sub>CTX-M-24</sub>-Harboring Virulence Plasmid.

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