scholarly journals Carriage of distinct blaKPC-2 and blaOXA-48 plasmids in a single ST11 hypervirulent Klebsiella pneumoniae isolate in Egypt

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yanxian Yang ◽  
Yongqiang Yang ◽  
Mohamed Abd El-Gawad El-Sayed Ahmed ◽  
Mingyang Qin ◽  
Ruowen He ◽  
...  
Keyword(s):  
Galleria Mellonella ◽  
Carbapenem Resistance ◽  
Conjugative Plasmid ◽  
Sequencing Analysis ◽  
Significant Morbidity ◽  
Carbapenem Resistant ◽  
Transmission Mechanisms ◽  
Transfer Genes ◽  
Serious Infections ◽  
Almost All

Abstract Background Carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) causes serious infections with significant morbidity and mortality. However, the epidemiology and transmission mechanisms of CR-hvKP and the corresponding carbapenem-resistant plasmids require further investigation. Herein, we have characterized an ST11 K. pneumoniae strain EBSI041 from the blood sample encoding both hypervirulence and carbapenem resistance phenotypes from a patient in Egypt. Results K. pneumoniae strain EBSI041 showed multidrug-resistance phenotypes, where it was highly resistant to almost all tested antibiotics including carbapenems. And hypervirulence phenotypes of EBSI041 was confirmed by the model of Galleria mellonella infection. Whole-genome sequencing analysis showed that the hybrid plasmid pEBSI041-1 carried a set of virulence factors rmpA, rmpA2, iucABCD and iutA, and six resistance genes aph(3′)-VI, armA, msr(E), mph(E), qnrS, and sul2. Besides, blaOXA-48 and blaSHV-12 were harboured in a novel conjugative IncL-type plasmid pEBSI041-2. The blaKPC-2-carrying plasmid pEBSI041-3, a non-conjugative plasmid lacking the conjugative transfer genes, could be transferred with the help of pEBSI041-2, and the two plasmids could fuse into a new plasmid during co-transfer. Moreover, the emergence of the p16HN-263_KPC-like plasmids is likely due to the integration of pEBSI041-3 and pEBSI041-4 via IS26-mediated rearrangement. Conclusion To the best of our knowledge, this is the first report on the complete genome sequence of KPC-2- and OXA-48-coproducing hypervirulent K. pneumoniae from Egypt. These results give new insights into the adaptation and evolution of K. pneumoniae during nosocomial infections.

scholarly journals Multicity Outbreak of Carbapenem-Resistant Acinetobacter baumannii Isolates Producing the Carbapenemase OXA-40

2006 ◽  
Vol 50 (9) ◽  
pp. 2941-2945 ◽  
Author(s):  
Karen Lolans ◽  
Thomas W. Rice ◽  
L. Silvia Munoz-Price ◽  
John P. Quinn
Keyword(s):  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
The United States ◽  
Nucleotide Sequencing ◽  
Sequencing Analysis ◽  
Carbapenem Resistant ◽  
Extended Care ◽  
Care Facilities ◽  
High Level ◽  
First Time

ABSTRACT During 2005 we detected a multicity outbreak of infections or colonization due to high-level imipenem-resistant Acinetobacter baumannii (MIC, 64 μg/ml). One hundred isolates from diverse sources were obtained from seven acute-care hospitals and two extended-care facilities; 97% of the isolates belonged to one clone. Susceptibility testing of the first 42 isolates (January to April 2005) revealed broad resistance profiles. Half of the isolates were susceptible to ceftazidime, with many isolates susceptible only to colistin. The level of AmpC β-lactamase expression was stronger in isolates resistant to ceftazidime. PCR and subsequent nucleotide sequencing analysis identified bla OXA-40. The presence of an OXA-40 β-lactamase in these isolates correlated with the carbapenem resistance. By Southern blot analysis, a bla OXA-40-specific probe revealed that the gene was both plasmid and chromosomally located. This is the first time in the United States that such carbapenem resistance in A. baumannii has been attributable to a carbapenemase.

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 OmpK26, a Novel Porin Associated with Carbapenem Resistance in Klebsiella pneumoniae

2011 ◽  
Vol 55 (10) ◽  
pp. 4742-4747 ◽  
Author(s):  
Laura García-Sureda ◽  
Antonio Doménech-Sánchez ◽  
Mariette Barbier ◽  
Carlos Juan ◽  
Joan Gascó ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Outer Membrane Proteins ◽  
Systemic Infection ◽  
Carbapenem Resistance ◽  
Resistant Isolate ◽  
Identical Result ◽  
Sequencing Analysis ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACTClinical isolates ofKlebsiella pneumoniaeresistant to carbapenems are being isolated with increasing frequency. Loss of the expression of the major nonspecific porins OmpK35/36 is a frequent feature in these isolates. In this study, we looked for porins that could compensate for the loss of the major porins in carbapenem-resistant organisms. Comparison of the outer membrane proteins from twoK. pneumoniaeclinical isogenic isolates that are susceptible (KpCS-1) and resistant (KpCR-1) to carbapenems revealed the absence of OmpK35/36 and the presence of a new 26-kDa protein in the resistant isolate. An identical result was obtained when another pair of isogenic isolates that are homoresistant (Kpn-3) and heteroresistant (Kpn-17) to carbapenems were compared. Mass spectrometry and DNA sequencing analysis demonstrated that this new protein, designated OmpK26, is a small monomeric oligogalacturonate-specific porin that belongs to the KdgM family of porins. Insertion-duplication mutagenesis of the OmpK26 coding gene,yjhA, in the carbapenem-resistant, porin-deficient isolate KpCR-1 caused the expression of OmpK36 and the reversion to the carbapenem-susceptible phenotype, suggesting that OmpK26 is indispensable for KpCR-1 to lose OmpK36 and become resistant to these antibiotics. Moreover, loss of the major porin and expression of OmpK26 reducedin vitrofitness and attenuated virulence in a murine model of acute systemic infection. Altogether, these results indicate that expression of the oligogalacturonate-specific porin OmpK26 compensates for the absence of OmpK35/36 and allows carbapenem resistance inK. pneumoniaebut cannot restore the fitness of the microorganism.

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 165. Cefiderocol Treatment for Serious Infections Caused by Carbapenem-resistant Bacteria: Post-hoc Analysis of Outcomes by Pathogen in the CREDIBLE-CR Study

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S212-S212
Author(s):  
Yuko Matsunaga ◽  
Mari Ariyasu ◽  
Miki Takemura ◽  
Yoshinori Yamano ◽  
Kiichiro Toyoizumi ◽  
...  
Keyword(s):  
Clinical Cure ◽  
Carbapenem Resistance ◽  
Bloodstream Infections ◽  
Resistant Bacteria ◽  
Open Label ◽  
Gram Negative ◽  
Mitt Population ◽  
Carbapenem Resistant ◽  
Serious Infections ◽  
Tract Infections

Abstract Background The efficacy and safety of cefiderocol (CFDC), a novel siderophore cephalosporin, for the treatment of serious infections due to carbapenem-resistant (CR) Gram-negative pathogens was assessed in the CREDIBLE-CR study. The current analysis evaluated clinical and microbiological outcomes by baseline CR pathogen. Methods An open-label, prospective, randomised 2:1, Phase 3 study (CREDIBLE-CR; NCT02714595) was conducted in adult patients with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, bloodstream infections or sepsis, and complicated urinary tract infections caused by CR Gram-negative pathogens. Patients received either intravenous (IV) CFDC 2g, q8h, 3-h infusion, or IV best available therapy (BAT: up to 3 drugs in combination), for 7–14 days (extendable to 21 days). Clinical and microbiological outcomes were assessed in the CR microbiological intent-to-treat (CR-MITT) population by CR pathogen, baseline MIC and by mechanism of carbapenem resistance at test of cure (TOC). Only summary statistics were collected. Results In the CR-MITT population (CFDC N=80; BAT N=38), Acinetobacter baumannii (46.3% and 44.7%), Klebsiella pneumoniae (33.8% and 31.5%), and Pseudomonas aeruginosa (15% and 26%) were the most frequent pathogens in CFDC and BAT arms, respectively. For all CR pathogens, clinical cure rates were achieved in 52.5% in the CFDC arm and 50.0% in the BAT arm at TOC; rates were similar between treatment arms by baseline CR pathogen (Table 1). Numerically higher clinical cure and microbiological outcomes were observed with CFDC for Enterobacterales (Table 1), especially against NDM-producing bacteria or those with porin-channel mutations (Table 1). CFDC MIC values ranged between ≤0.03 and 4 μg/mL, except for one pathogen (Table 2). Microbiological outcomes for CR A. baumannii, CR K. pneumoniae, and CR P. aeruginosa at TOC by baseline MICs of ≤4 μg/mL ranged between 0–40%, 0–100%, and 0–100%, respectively; at MIC ≤4 μg/mL, clinical and microbiological outcomes were equal (Table 2). Conclusion CFDC, via a novel mechanism of entry and its stability against β-lactamases, was effective against serious infections caused by CR pathogens with various resistance mechanisms or baseline MIC values. Disclosures Yuko Matsunaga, MD, Shionogi Inc. (Employee) Mari Ariyasu, BPharm, Shionogi & Co., Ltd. (Employee) Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Kiichiro Toyoizumi, PhD, Shionogi & Co., Ltd. (Employee) Masahiro Kinoshita, MPharm, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Tsutae Den Nagata, MD, Shionogi & Co., Ltd. (Employee)

scholarly journals Association Between Carbapenem Resistance and Mortality Among Adult, Hospitalized Patients With Serious Infections Due to Enterobacteriaceae: Results of a Systematic Literature Review and Meta-analysis

2018 ◽  
Vol 5 (7) ◽  
Author(s):  
Amber Martin ◽  
Kyle Fahrbach ◽  
Qi Zhao ◽  
Thomas Lodise
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Meta Analysis ◽  
Carbapenem Resistance ◽  
Hospitalized Patients ◽  
Mortality Data ◽  
Carbapenem Resistant ◽  
Serious Infections ◽  
New Antibiotics ◽  
Appropriate Therapy

Abstract This study quantified mortality associated with serious infections caused by carbapenem-resistant (CRE) and carbapenem-susceptible Enterobacteriaceae (CSE). A systematic literature review was conducted, evaluating outcomes in hospitalized patients with CRE infections from a blood, urinary, pulmonary, or intra-abdominal source. A meta-analysis (MA) calculating odds ratios (ORs) for mortality was performed. Twenty-two studies met the criteria for inclusion in the MA: 12 included mortality data for CRE vs CSE populations. Compared with CSE, CRE was associated with a significantly higher risk of overall mortality (OR, 3.39; 95% confidence interval [CI], 2.35–4.89), as was monotherapy (vs combination therapy) treatment of patients with CRE infections (OR, 2.19; 95% CI, 1.00–4.80). These results document the increased mortality associated with serious CRE infections compared with CSE infections among hospitalized adults. It will be important to reevaluate the mortality in CRE and CSE populations, especially among patients who receive early appropriate therapy, as new antibiotics become available.

scholarly journals Current Promising Antibiotics and Future Approaches in Combating Carbapenemase-Producing Enterobacteriaceae

Proceedings ◽  
2021 ◽  
Vol 66 (1) ◽  
pp. 25
Author(s):  
Corneliu Ovidiu Vrancianu ◽  
Elena Georgiana Dobre ◽  
Irina Gheorghe ◽  
Ilda Barbu ◽  
Roxana Elena Cristian ◽  
...  
Keyword(s):  
Carbapenem Resistance ◽  
Healthcare Associated Infections ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
High Incidence ◽  
Low Probability ◽  
Almost All ◽  
Healthcare Associated ◽  
Review Current ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem-resistant (CR) Gram-negative bacilli, including Enterobacteriaceae and the non-fermenters, represent the most notorious pathogens due to the high incidence of morbidity and mortality, especially in immunocompromised patients in intensive care units. Carbapenem resistance is mainly associated with the production of carbapenemases, which are β-lactamases belonging to different Ambler classes (A, B, D) that can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent β-lactamases, hydrolyzing a wide variety of β-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major issues associated with carbapenemase production are both clinical, posing significant challenges in the treatment of healthcare-associated infections by compromising the activity of the last-resort antibiotics, and epidemiological, due to their dissemination across almost all geographic regions. An important advancement is a handful of newly launched antibiotics targeting some of the current most problematic Gram-negative pathogens, namely carbapenem-resistant Enterobacteriaceae (CRE). The most appropriate antimicrobial therapy to treat CRE infections is still controversial. Combination therapy is preferred over monotherapy due to its broad-spectrum coverage, synergic activity, and low probability of selecting resistance. In this mini-review, current and future promising antibiotics that are currently under investigation for winning the war against the emerging CRE are discussed.

scholarly journals Rapid Increase in Prevalence of Carbapenem-ResistantEnterobacteriaceae(CRE) and Emergence of Colistin Resistance Genemcr-1in CRE in a Hospital in Henan, China

2018 ◽  
Vol 56 (4) ◽  
Author(s):  
Yi Li ◽  
Qiao-ling Sun ◽  
Yingbo Shen ◽  
Yangjunna Zhang ◽  
Jun-wen Yang ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Clinical Samples ◽  
New Delhi ◽  
Colistin Resistance ◽  
Large Hospital ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Recent Emergence ◽  
Almost All

ABSTRACTThe global spread of carbapenem-resistantEnterobacteriaceae(CRE) is one of the most severe threats to human health in a clinical setting. The recent emergence of plasmid-mediated colistin resistance genemcr-1among CRE strains greatly compromises the use of colistin as a last resort for the treatment of infections caused by CRE. This study aimed to understand the current epidemiological trends and characteristics of CRE from a large hospital in Henan, the most populous province in China. From 2014 to 2016, a total of 7,249Enterobacteriaceaeisolates were collected from clinical samples, among which 18.1% (1,311/7,249) were carbapenem resistant. Carbapenem-resistantKlebsiella pneumoniaeand carbapenem-resistantEscherichia coliwere the two most common CRE species, withKlebsiella pneumoniaecarbapenemases (KPC) and New Delhi metallo-β-lactamases (NDM), respectively, responsible for the carbapenem resistance of the two species. Notably, >57.0% (n= 589) of theK. pneumoniaeisolates from the intensive care unit were carbapenem resistant. Furthermore,blaNDM-5andmcr-1were found to coexist in oneE. coliisolate, which exhibited resistance to almost all tested antibiotics. Overall, we observed a significant increase in the prevalence of CRE isolates during the study period and suggest that carbapenems may no longer be considered to be an effective treatment for infections caused byK. pneumoniaein the studied hospital.

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 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.

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