Identification of a novel conjugative mcr-8.2-bearing plasmid in an almost pan-resistant hypermucoviscous Klebsiella pneumoniae ST11 isolate with enhanced virulence

Qin, Shangshang; Zhang, Chunli; Schwarz, Štefan; Li, Leyuan; Dong, Huiyue; Yao, Hong; Du, Xiang-Dang

doi:10.1093/jac/dkaa226

Cited by 11 publications

(5 citation statements)

References 9 publications

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“… 6 A novel conjugative mcr-8.2 -bearing plasmid was identified in an almost pan-resistant hypermucoviscous Klebsiella pneumoniae ST11 isolate in Henan. 7 However, overall, the report about mcr in human-derived E. coli and K. pneumoniae isolates was primarily focused outside Henan.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism of Polymyxin Resistance in Multidrug-Resistant Klebsiella pneumoniae and Escherichia coli Isolates from Henan Province, China: A Multicenter Study

Yan¹,

Qi²,

Zhu³

et al. 2021

IDR

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To evaluate polymyxin-resistant Klebsiella pneumoniae and Escherichia coli prevalence and characteristics in the Henan province, China. Materials and Methods: A total of 2301 bacterial isolates collected at six hospitals were assessed. Their response to polymyxin was evaluated by minimum inhibitory concentration (MIC) analysis, and the mobilized colistin resistance (mcr) and carbapenemase gene were explored. Mutations on mgrB, phoPQ, pmrAB, and crrAB in polymyxin-resistant K. pneumoniae were detected by PCR. phoP, phoQ, pmrK, pmrA, pmrB, and pmrC transcriptional levels were quantified by RT-qPCR. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing were performed to determine the phylogenetic relationship between the polymyxin-resistant isolates. Results: Of the E. coli and K. pneumoniae isolates identified, 0.3% and 1.4% were polymyxin-resistant, respectively, with MICs of 4-64 μg/mL. All polymyxin-resistant isolates were susceptible to tigecycline. Four E. coli isolates were mcr-1-positive and one was carbapenem-resistant, carrying bla NDM-5 and mcr-1. One K. pneumoniae isolate was mcr-1-positive and nine were carbapenem-resistant (PRCRKP), carrying bla KPC-2 but not mcr-1.The five E. coli isolates belonged to four sequence types (ST2, ST132, ST632, and ST983). All PRCRKP isolates belonged to ST11. However, all 16 isolates belonged to different PFGE types with <95% genetic similarity. Insertion sequences in mgrB were detected in nine (81.8%) polymyxin-resistant K. pneumoniae samples. Colistin resistance was linked with pmrHFIJKLM operon upregulation, with phoP, phoQ, and pmrK being overexpressed in all but one of the polymyxin-resistant K. pneumoniae samples. Furthermore, 33.3% of patients carrying polymyxin-resistant isolates had previously used polymyxin, and 66.7% patients displayed good clinical outcomes. Conclusion:The K. pneumoniae polymyxin resistance rate was slightly higher than that of E. coli and mcr-1 was more common in E. coli than in K. pneumoniae. Moreover, the insertion of ISkpn14 into mgrB may be the main contributor to polymyxin-resistance in K. pneumoniae in Henan.

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Section: Introductionmentioning

confidence: 99%

Molecular Mechanism of Polymyxin Resistance in Multidrug-Resistant Klebsiella pneumoniae and Escherichia coli Isolates from Henan Province, China: A Multicenter Study

Yan¹,

Qi²,

Zhu³

et al. 2021

IDR

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“…The mouse bacteremia infection model was used to assess the virulence of various K. pneumoniae strains as described previously (Yang et al, 2019 ). The non-hypermucoviscous ST1-K19 K. pneumoniae strain, KP18-208, was used as the control for low virulence (Qin et al, 2020 ), while an ST268-K20 K. penumoniae strain, KP19-2065, served as the control for hypervirulence. Mice in each group were infected intravenously with 5.0 × 10 5 CFU and 5.0 × 10 6 CFU of each K. pneumoniae strain tested.…”

Section: Methodsmentioning

confidence: 99%

Molecular characterization of hybrid virulence plasmids in ST11-KL64 KPC-2-producing multidrug-resistant hypervirulent Klebsiella pneumoniae from China

Zhang,

Li,

Zhao

et al. 2024

Front. Microbiol.

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IntroductionCarbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) strains combining virulence and multidrug resistance (MDR) features pose a great public health concern. The aim of this study is to explore the evolutionary characteristics of virulence in CR-HvKP by investigating the genetic features of resistance and virulence hybrid plasmids.MethodsThe resistance and virulence phenotypes were determined by using antimicrobial susceptibility testing and the mouse bacteremia infection model, respectively. Plasmid profiles were investigated by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting, conjugation assay, and whole genome sequencing (WGS). Bioinformatics tools were used to uncover the genetic features of the resistance and virulence hybrid plasmids.ResultsTwo ST11-KL64 CRKP clinical isolates (KP18-3-8 and KP18-2079), which exhibited enhanced virulence compared with the classic CRKP, were detected positive for blaKPC−2 and rmpA2. The virulence level of the hypermucoviscous strain KP18-3-8 was higher than that of KP18-2079. S1-PFGE, Southern hybridization and WGS analysis identified two novel hybrid virulence plasmids in KP18-3-8 (pKP1838-KPC-vir, 228,158 bp) and KP18-2079 (pKP1838-KPC-vir, 182,326 bp), respectively. The IncHI1B/repB-type plasmid pKP1838-KPC-vir co-harboring blaKPC−2 and virulence genes (rmpA2, iucABCD and iutA) but lacking type IV secretion system could transfer into non-hypervirulent ST11 K. pneumoniae with the assistance of a helper plasmid in conjugation. The IncFII/IncR-type virulence plasmid pKP18-2079-vir may have been generated as a result of recombination between a typical pLVPK-like virulence plasmid and an MDR plasmid.ConclusionOur studies further highlight co-evolution of the virulence and resistance plasmids in ST11-CRKP isolates. Close surveillance of such hybrid virulence plasmids in clinical K. pneumoniae should be performed.

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“…Of note, mcr-1-positive strains have also emerged in the Henan province, including in pigderived Escherichia coli isolates [5]. In fact, clinical E. coli isolates co-producing bla NDM and mcr-1 were previously reported by our laboratory [6], and a novel conjugative mcr-8.2-bearing plasmid was identi ed in an almost pan-resistant hypermucoviscous Klebsiella pneumoniae ST11 isolate [7]. However, overall, the reports of mcr in human-derived E. coli and K. pneumoniae isolates are mainly centred outside of Henan.…”

Section: Introductionmentioning

confidence: 90%

Emergence of mobilized colistin resistance-1 in multidrug-resistant Klebsiella pneumoniae and Escherichia coli isolates from the Henan province in China: a multicentre study

Yan

et al. 2021

Preprint

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Background The increased clinical use of polymyxin led to the emergence of polymyxin-resistant strains, especially those carrying plasmid-borne mobilized colistin resistance (mcr) gene variants. In this study, we aimed to evaluate the prevalence and characteristics of polymyxin-resistant Klebsiella pneumoniae and Escherichia coli isolates from the Henan province, China. Methods A total of 16 polymyxin-resistant isolates among 2301 E. coli and K. pneumoniae isolates collected in 6 local hospitals in the Henan province were studied. The isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the minimum inhibitory concentrations (MICs) were determined using the microbroth dilution technique. Polymyxin-resistant isolates were further analysed for mcr-1 and carbapenemase-mediated resistance using the modified carbapenem inactivation method, the ethylenediaminetetraacetic acid-modified carbapenem inactivation method, and polymerase chain reaction. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed to disclose the phylogenetic relationships of the polymyxin-resistant isolates. The clinical characteristics of patients infected with the polymyxin-resistant isolates were also retrospectively analysed. Results 5/1499 (0.3%) and 11/802 (1.4%) E. coli and K. pneumoniae isolates, respectively, were polymyxin-resistant. The MICs of polymyxin were in the range of 4–64 µg/mL and all of the 16 polymyxin-resistant isolates were susceptible to tigecycline. Additionally, four of the five E. coli polymyxin-resistant isolates were mcr-1 positive; one of them was also carbapenem-resistant, carrying blaNDM−5. Conversely, only 1/11 K. pneumoniae isolates was mcr-1 positive, while 9 polymyxin-resistant isolates were also carbapenem-resistant (PRCRKP), carrying blaKPC−2 but not mcr-1. MLST results showed that the five E. coli isolates belonged to four sequence types (STs), including ST2, ST132, ST632, and ST983, while all PRCRKP isolates belonged to ST11. However, all 16 isolates showed different PFGE types using a genetic similarity of ≥ 95%. Furthermore, 33.3% (5/15) of the patients carrying polymyxin-resistant K. pneumoniae isolates showed a history of polymyxin use, and 10/15 (66.7%) patients displayed good clinical outcomes. Conclusion The polymyxin resistance rate of K. pneumoniae was slightly higher than that of E. coli in the Henan province; however, mcr-1 was only detected in one K. pneumoniae isolate. Thus, close monitoring is needed to prevent and control the spread of PRCRKP.

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Identification of a novel conjugative mcr-8.2-bearing plasmid in an almost pan-resistant hypermucoviscous Klebsiella pneumoniae ST11 isolate with enhanced virulence

Cited by 11 publications

References 9 publications

Molecular Mechanism of Polymyxin Resistance in Multidrug-Resistant Klebsiella pneumoniae and Escherichia coli Isolates from Henan Province, China: A Multicenter Study

Molecular Mechanism of Polymyxin Resistance in Multidrug-Resistant Klebsiella pneumoniae and Escherichia coli Isolates from Henan Province, China: A Multicenter Study

Molecular characterization of hybrid virulence plasmids in ST11-KL64 KPC-2-producing multidrug-resistant hypervirulent Klebsiella pneumoniae from China

Emergence of mobilized colistin resistance-1 in multidrug-resistant Klebsiella pneumoniae and Escherichia coli isolates from the Henan province in China: a multicentre study

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