scholarly journals The carbapenem resistance gene blaOXA-23 is disseminated by a conjugative plasmid containing the novel transposon Tn6681 in Acinetobacter johnsonii M19

2020 ◽  
Author(s):  
Gongli Zong ◽  
Chuanqing Zhong ◽  
Jiafang Fu ◽  
Yu Zhang ◽  
Peipei Zhang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Resistance Gene ◽  
Carbapenem Resistance ◽  
Conjugative Plasmid ◽  
The Novel ◽  
Illumina Hiseq ◽  
Discovery Studio ◽  
Acinetobacter Johnsonii ◽  
Type Iv ◽  
Carbapenem Resistant

Abstract Background: Carbapenem resistant Acinetobacter species have caused great difficulties in clinical therapy in the worldwide. Here we describe an Acinetobacter johnsonii M19 with a novel blaOXA-23 containing transposon Tn6681 on the conjugative plasmid pFM-M19 and the ability to transfer carbapenem resistance.Methods: A. johnsonii M19 was isolated under selection with 8 mg/L meropenem from hospital sewage, and the minimum inhibitory concentrations (MICs) for the representative carbapenems imipenem, meropenem and ertapenem were determined. The genome of A. johnsonii M19 was sequenced by PacBio RS II and Illumina HiSeq 4000 platforms. A homologous model of OXA-23 was generated, and molecular docking models with imipenem, meropenem and ertapenem were constructed by Discovery Studio 2.0. Type IV secretion system and conjugation elements were identified by the Pathosystems Resource Integration Center (PATRIC) server and the oriTfinder. Mating experiments were performed to evaluate transfer of OXA-23 to Escherichia coli 25DN.Results: MICs of A. johnsonii M19 for imipenem, meropenem and ertapenem were 128 mg/L, 48 mg/L and 24 mg/L, respectively. Genome sequencing identified plasmid pFM-M19, which harbours the carbapenem resistance gene blaOXA-23 within the novel transposon Tn6681. Molecular docking analysis indicated that the elongated hydrophobic tunnel of OXA-23 provides a hydrophobic environment and that Lys-216, Thr-217, Met-221 and Arg-259 were the conserved amino acids bound to imipenem, meropenem and ertapenem. Furthermore, pFM-M19 could transfer blaOXA-23 to E. coli 25DN by conjugation, resulting in carbapenem-resistant transconjugants. Conclusions: Our investigation showed that A. johnsonii M19 is a source and disseminator of blaOXA-23 and carbapenem resistance. The ability to transfer blaOXA-23 to other species by the conjugative plasmid pFM-M19 raises the risk of spread of carbapenem resistance.

scholarly journals The carbapenem resistance gene blaOXA-23 is disseminated by a conjugative plasmid containing the novel transposon Tn6681 in Acinetobacter johnsonii M19

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Gongli Zong ◽  
Chuanqing Zhong ◽  
Jiafang Fu ◽  
Yu Zhang ◽  
Peipei Zhang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Resistance Gene ◽  
Carbapenem Resistance ◽  
Conjugative Plasmid ◽  
The Novel ◽  
Illumina Hiseq ◽  
Discovery Studio ◽  
Acinetobacter Johnsonii ◽  
Type Iv ◽  
Carbapenem Resistant

Abstract Background Carbapenem resistant Acinetobacter species have caused great difficulties in clinical therapy in the worldwide. Here we describe an Acinetobacter johnsonii M19 with a novel blaOXA-23 containing transposon Tn6681 on the conjugative plasmid pFM-M19 and the ability to transferand carbapenem resistance. Methods A. johnsonii M19 was isolated under selection with 8 mg/L meropenem from hospital sewage, and the minimum inhibitory concentrations (MICs) for the representative carbapenems imipenem, meropenem and ertapenem were determined. The genome of A. johnsonii M19 was sequenced by PacBio RS II and Illumina HiSeq 4000 platforms. A homologous model of OXA-23 was generated, and molecular docking models with imipenem, meropenem and ertapenem were constructed by Discovery Studio 2.0. Type IV secretion system and conjugation elements were identified by the Pathosystems Resource Integration Center (PATRIC) server and the oriTfinder. Mating experiments were performed to evaluate transfer of OXA-23 to Escherichia coli 25DN. Results MICs of A. johnsonii M19 for imipenem, meropenem and ertapenem were 128 mg/L, 48 mg/L and 24 mg/L, respectively. Genome sequencing identified plasmid pFM-M19, which harbours the carbapenem resistance gene blaOXA-23 within the novel transposon Tn6681. Molecular docking analysis indicated that the elongated hydrophobic tunnel of OXA-23 provides a hydrophobic environment and that Lys-216, Thr-217, Met-221 and Arg-259 were the conserved amino acids bound to imipenem, meropenem and ertapenem. Furthermore, pFM-M19 could transfer blaOXA-23 to E. coli 25DN by conjugation, resulting in carbapenem-resistant transconjugants. Conclusions Our investigation showed that A. johnsonii M19 is a source and disseminator of blaOXA-23 and carbapenem resistance. The ability to transfer blaOXA-23 to other species by the conjugative plasmid pFM-M19 raises the risk of spread of carbapenem resistance. Graphic abstract The carbapenem resistance gene blaOXA-23 is disseminated by a conjugative plasmid containing the novel transposon Tn6681 in Acinetobacter johnsonii M19.

scholarly journals The carbapenem resistance gene blaOXA-23 is disseminated by a conjugative plasmid containing the novel transposon Tn6681 in Acinetobacter johnsonii M19

2020 ◽  
Author(s):  
Gongli Zong ◽  
Chuanqing Zhong ◽  
Jiafang Fu ◽  
Yu Zhang ◽  
Peipei Zhang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Resistance Gene ◽  
Carbapenem Resistance ◽  
Conjugative Plasmid ◽  
The Novel ◽  
Illumina Hiseq ◽  
Discovery Studio ◽  
Acinetobacter Johnsonii ◽  
Type Iv ◽  
Carbapenem Resistant

Abstract Background Carbapenem resistant Acinetobacter species have caused great difficulties in clinical therapy in the worldwide. Here we describe an Acinetobacter johnsonii M19 with a novel blaOXA−23 containing transposon Tn6681 on the conjugative plasmid pFM-M19 and the ability to transferand carbapenem resistance. Methods A. johnsonii M19 was isolated under selection with 8 mg/L meropenem from hospital sewage, and the minimum inhibitory concentrations (MICs) for the representative carbapenems imipenem, meropenem and ertapenem were determined. The genome of A. johnsonii M19 was sequenced by PacBio RS II and Illumina HiSeq 4000 platforms. A homologous model of OXA-23 was generated, and molecular docking models with imipenem, meropenem and ertapenem were constructed by Discovery Studio 2.0. Type IV secretion system and conjugation elements were identified by the Pathosystems Resource Integration Center (PATRIC) server and the oriTfinder. Mating experiments were performed to evaluate transfer of OXA-23 to Escherichia coli 25DN. Results MICs of A. johnsonii M19 for imipenem, meropenem and ertapenem were 128 mg/L, 48 mg/L and 24 mg/L, respectively. Genome sequencing identified plasmid pFM-M19, which harbours the carbapenem resistance gene blaOXA−23 within the novel transposon Tn6681. Molecular docking analysis indicated that the elongated hydrophobic tunnel of OXA-23 provides a hydrophobic environment and that Lys-216, Thr-217, Met-221 and Arg-259 were the conserved amino acids bound to imipenem, meropenem and ertapenem. Furthermore, pFM-M19 could transfer blaOXA−23 to E. coli 25DN by conjugation, resulting in carbapenem-resistant transconjugants. Conclusions Our investigation showed that A. johnsonii M19 is a source and disseminator of blaOXA−23 and carbapenem resistance. The ability to transfer blaOXA−23 to other species by the conjugative plasmid pFM-M19 raises the risk of spread of carbapenem resistance.

Integration of the blaNDM-1 carbapenemase gene into a novel SXT/R391 integrative and conjugative element in Proteus vulgaris

2020 ◽  
Vol 75 (6) ◽  
pp. 1439-1442
Author(s):  
Ling-Han Kong ◽  
Rong Xiang ◽  
Yu-Long Wang ◽  
Shun-Kang Wu ◽  
Chang-Wei Lei ◽  
...  
Keyword(s):  
Resistance Gene ◽  
Resistance Genes ◽  
Bioinformatics Analysis ◽  
Carbapenem Resistance ◽  
Resistance Determinant ◽  
Proteus Vulgaris ◽  
Genetic Environment ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Integrative And Conjugative Element

Abstract Objectives To characterize the genetic environment of the carbapenem resistance determinant in Proteus vulgaris of swine origin. Methods The carbapenem-resistant P. vulgaris strain BC22 was isolated from a faecal swab from a diseased pig with diarrhoea in Sichuan Province of China in 2018. The presence of carbapenemase genes was screened by PCR. WGS and bioinformatics analysis were performed to analyse the genetic environment of the carbapenem resistance determinant. Results P. vulgaris strain BC22 was found to harbour the carbapenemase gene blaNDM-1. WGS data revealed that blaNDM-1 was located in a truncated ISAba125 composite transposon. The carbapenem resistance gene blaNDM-1 and 20 other resistance genes, including the multiresistance gene cfr and the bifunctional aminoglycoside/quinolone resistance gene aac(6′)-lb-cr, were located in a novel SXT/R391 integrative and conjugative element (ICE). This new SXT/R391 ICE of 148.7 kb was chromosomally located, and could be transferred to Escherichia coli. Conclusions Here, we report a carbapenemase gene, blaNDM-1, integrated into an SXT/R391 ICE. Our study highlights that this SXT/R391 ICE may facilitate the dissemination of clinically important resistance genes such as blaNDM-1, cfr and aac(6′)-lb-cr.

scholarly journals Detection of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae producing NDM-1 in Lebanon

2012 ◽  
Vol 6 (05) ◽  
pp. 457-461 ◽  
Author(s):  
Rima I El-Herte ◽  
George F Araj ◽  
Ghassan M Matar ◽  
Maysa Baroud ◽  
Zeina A Kanafani ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
New Delhi ◽  
Beta Lactamase ◽  
The Novel ◽  
First Report ◽  
Carbapenem Resistant ◽  
Lactamase Gene ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem resistance has been encountered globally with poor outcome of infected patients. NDM-1 (New Delhi metallo-beta-lactamase) gene containing organisms have emerged and are now spreading in all continents. This is the first report of Iraqi patients referred to Lebanon from whom carbapenem resistant Enterobacteriaceae were recovered. The genes involved in carbapenem resistance were bla-OXA-48   and the novel NDM-1. This report highlights the alarming introduction of such resistance among Enterobacteriaecae to this country.

GPC-1, a novel class A carbapenemase detected in a clinical Pseudomonas aeruginosa isolate

2020 ◽  
Vol 75 (4) ◽  
pp. 911-916 ◽  
Author(s):  
Jennifer Schauer ◽  
Sören G Gatermann ◽  
Daniel Hoffmann ◽  
Lars Hupfeld ◽  
Niels Pfennigwerth
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Heterologous Expression ◽  
Biochemical Characterization ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Amino Acid Identity ◽  
The Novel ◽  
Bacterial Strains ◽  
Class A ◽  
Carbapenem Resistant

Abstract Objectives To investigate the carbapenem resistance mechanism of a carbapenem-resistant clinical Pseudomonas aeruginosa isolate. Methods A carbapenem-resistant P. aeruginosa isolate was recovered from a tracheal swab from a patient of a general ward in central Germany. Various phenotypic tests confirmed production of a carbapenemase that could not be identified further by PCR. A novel bla gene was identified by WGS and its carbapenemase activity was verified by heterologous expression in an Escherichia coli cloning strain. Kinetic parameters of the novel β-lactamase were determined by spectrophotometric measurements using purified enzyme. Results WGS confirmed the presence of a novel class A carbapenemase. The novel bla gene was named GPC-1 (GPC standing for German Pseudomonas Carbapenemase) and exhibited 77% amino acid identity to BKC-1. WGS also showed that blaGPC-1 was located on the chromosome surrounded by multiple ISs as part of a 26 kb genetic island. Heterologous expression of GPC-1 in E. coli TOP10 led to increased MICs of penicillins, oxyimino-cephalosporins, aztreonam and imipenem, but not of meropenem or ertapenem. Spectrophotometric measurements supported the MIC studies, but detected a slight hydrolysis of ertapenem and meropenem when using high concentrations of purified enzyme. Conclusions The biochemical characterization of GPC-1 emphasizes the ongoing emergence of novel carbapenemases. Strains expressing a weak carbapenemase like GPC-1 might go unrecognized by routine diagnostics due to low MICs for the bacterial strains producing such enzymes.

scholarly journals Clinical evolution of ST11 carbapenem resistant and hypervirulent Klebsiella pneumoniae

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Miaomiao Xie ◽  
Xuemei Yang ◽  
Qi Xu ◽  
Lianwei Ye ◽  
Kaichao Chen ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
High Mortality ◽  
Genome Analysis ◽  
Direct Evidence ◽  
Carbapenem Resistance ◽  
Conjugative Plasmid ◽  
Evolutionary Mechanisms ◽  
Clinical Evolution ◽  
Carbapenem Resistant

AbstractCarbapenem-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.

scholarly journals Evaluation of Clonality and Carbapenem Resistance Mechanisms among Acinetobacter baumannii-Acinetobacter calcoaceticus Complex and Enterobacteriaceae Isolates Collected in European and Mediterranean Countries and Detection of Two Novel β-Lactamases, GES-22 and VIM-35

2014 ◽  
Vol 58 (12) ◽  
pp. 7358-7366 ◽  
Author(s):  
Mariana Castanheira ◽  
Sarah E. Costello ◽  
Leah N. Woosley ◽  
Lalitagauri M. Deshpande ◽  
Todd A. Davies ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
Acinetobacter Calcoaceticus ◽  
Resistance Mechanisms ◽  
The Novel ◽  
Intrinsic Resistance ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Mediterranean Countries ◽  
Class 1

ABSTRACTWe evaluated doripenem-resistantAcinetobacter baumannii-Acinetobacter calcoaceticuscomplex (ACB;n= 411) andEnterobacteriaceae(n= 92) isolates collected from patients from 14 European and Mediterranean countries during 2009 to 2011 for the presence of carbapenemase-encoding genes and clonality. Following susceptibility testing, carbapenem-resistant (doripenem MIC, >2 μg/ml) isolates were screened for carbapenemases. New β-lactamase genes were expressed in a common background and susceptibility was tested. Class 1 integrons were sequenced. Clonality was evaluated by pulsed-field gel electrophoresis and multilocus sequence typing (Pasteur scheme). Relative expression of β-lactam intrinsic resistance mechanisms was determined for carbapenemase-negativeEnterobacteriaceae. ACB andEnterobacteriaceaedisplayed 58.9 and 0.9% doripenem resistance, respectively.blaOXA-23,blaOXA-58, andblaOXA-24/OXA-40were detected among 277, 77, and 29 ACB, respectively (in 8, 6, and 5 countries). Ten Turkish isolates carriedblaGES-11orblaGES-22. GES-22 (G243A and M169L mutations in GES-1) had an extended-spectrum β-lactamase profile. A total of 33 clusters of ≥2 ACB isolates were observed, and 227 isolates belonged to sequence type 2/international clone II. Other international clones were limited to Turkey and Israel. Doripenem-resistantEnterobacteriaceaeincreased significantly (0.7 to 1.6%), and 15blaKPC-2- and 22blaKPC-3-carrying isolates, mostly belonging to clonal complexes 11 and 258, were observed.Enterobacteriaceaeisolates producing OXA-48 (n= 16; in Turkey and Italy), VIM-1 (n= 10; in Greece, Poland, and Spain), VIM-26 (n= 1; in Greece), and IMP-19, VIM-4, and the novel VIM-35 (n= 1 each from Poland) were detected. VIM-35 had one substitution compared to VIM-1 (A235T) and a similar susceptibility profile. One or more resistance mechanisms were identified in 4/6 carbapenemase-negativeEnterobacteriaceae. This broad evaluation confirms results from country-specific surveys and shows a highly diverse population of carbapenemase-producing ACB andEnterobacteriaceaein Europe and Mediterranean countries.

scholarly journals The Acquisition of Resistance to Carbapenem and Macrolide-mediated Quorum Sensing Inhibition byPseudomonas aeruginosavia a Novel Integrative and Conjugative Element ICETn43716385

2017 ◽  
Author(s):  
Yichen Ding ◽  
Jeanette Teo ◽  
Daniela I. Drautz-Moses ◽  
Stephan Christoph Schuster ◽  
Michael Givskov ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Resistance Gene ◽  
Carbapenem Resistance ◽  
World Health ◽  
Fourth Generation ◽  
Sequencing Analysis ◽  
Quorum Sensing Inhibition ◽  
Carbapenem Resistant ◽  
Integrative And Conjugative Element

AbstractPseudomonas aeruginosacan cause persistant and life-threatening infections in immunocompromised patients. Carbapenems are the first-line agents to treatP. aeruginosainfections; therefore, the emergence of carbapenem-resistantP. aeruginosastrains has greatly challenged effective antibiotic therapy. In this study, we characterised the full-length genomes of two carbapenem resistantP. aeruginosaclinical isolates that produce the carbapebemase New Delhi metallo-β-lactamase-1 (NDM-1). We found that theblaNDM-1gene is encoded by a novel intergrative and conjugative element (ICE) ICETn43716385, which also carries the macrolide resistance genemsr(E)and the florfenicol resistance genefloR. Themsr(E)gene has rarely been described inP. aeruginosagenomes. To investigate the functional roles ofmsr(E)inP. aeruginosa, we exogeneously expressed this gene inP. aeruginosalaboratory strains and found that the acquisition ofmsr(E)could abolish the azithromycin-mediated quorum sensing inhibitionin vitroand the anti-Pseudomonas effect of azithromycinin vivo. In addition, the expression ofmsr(E)almost completely restored the azithromycin-affectedP. aeruginosatranscriptome, as shown by our RNA sequencing analysis. We present the first evidence ofblaNDM-1to be carried by intergrative and conjugative elements, and the first evidence of co-transfer of carbapenem resistance and the resistance to macrolide-mediated quorum sensing inhibition intoP. aeruginosagenomes.ImportanceCarbapenem resistantP. aeruginosahas recently been listed as the top three most dangerous superbugs by World Health Organisation. The transmission ofblaNDM-1gene intoP. aeruginosacan cause extreme resistance to carbapenems and fourth generation cephalosporins, which greatly compromises the effectiveness of these antibiotics against Pseudomonas infections. However, the lack of complete genome sequence of NDM-1-producingP. aeruginosahas limited our understanding of the transmisibility ofblaNDM-1in this organism. Here we showed the co-transfer ofblaNDM-1andmsr(E)intoP. aeruginosagenome by a novel integrative and conjugative element (ICE). The acquisition of these two genes confersP. aeruginosawith resistance to carbapenem and macrolide-mediated quorum sensing inhibition, both of which are important treatment stretagies forP. aeruginosainfections. Our findings highlight the potential of ICEs in transmitting carbapenem resistance, and that the anti-virulence treatment ofP. aeruginosainfections by macrolides can be challenged by horizontal gene transfer.

scholarly journals Insights into the complete genomes of carbapenem-resistant Acinetobacter baumannii harbouring bla OXA-23, bla OXA-420 and bla NDM-1 genes using a hybrid-assembly approach

2020 ◽  
Vol 2 (8) ◽  
Author(s):  
Saranya Vijayakumar ◽  
Chand Wattal ◽  
Oberoi J.K. ◽  
Sanjay Bhattacharya ◽  
Karthick Vasudevan ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Type Species ◽  
Carbapenem Resistance ◽  
Complete Characterization ◽  
Hybrid Assembly ◽  
Content Type ◽  
Link Type ◽  
Type Iv ◽  
Carbapenem Resistant ◽  
Complete Genomes

Carbapenem resistance in Acinetobacter baumannii is due to bla OXA-23, which is endemic in India. Recently, the sporadic presence of bla OXA-58 as well as the occurrence of dual carbapenemases were observed. The mobility as well as the dissemination of these resistance genes were mainly mediated by various mobile genetic elements. The present study was aimed at characterizing the genetic arrangement of bla OXA-23, bla NDM-1 and bla OXA-58 identified in two complete genomes of carbapenem-resistant A. baumannii (CRAB). Complete genomes obtained using a hybrid-assembly approach revealed the accurate arrangement of Tn2006 with bla OXA-23, ISAba125 with bla NDM and ISAba3 with bla OXA-58. In addition, the association of IntI1 integrase with the bla CARB-2 gene and several virulence factors required for type-IV pili assembly, motility and biofilm formation have been identified. The current study provided deeper insight into the complete characterization of insertion sequences and transposons associated with the carbapenem-resistant genes using short reads of IonTorrent PGM and long reads of MinIon in A. baumannii .

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