Emergence of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae

AbstractColistin represents one of the very few available drugs for treating infections caused by carbapenem resistant Enterobacteriaceae (CRE). As such, the recent plasmid-mediated spread of the mobilized colistin resistance gene mcr-1 poses a significant public health threat requiring global monitoring and surveillance. In this work, we characterize the global distribution of mcr-1 using a dataset of 457 mcr-1 positive sequenced isolates consisting of currently publicly available mcr-1 carrying sequences combined with an additional 110 newly sequenced mcr-1 positive isolates from China. We find mcr-1 in a diversity of plasmid backgrounds but identify an immediate background common to all mcr-1 sequences. Our analyses establish that all mcr-1 elements in circulation descend from the same initial mobilization of mcr-1 by an ISApl1 transposon in the mid 2000s (2002-2008; 95% higher posterior density), followed by a dramatic demographic expansion, which led to its current global distribution. Our results provide the first systematic phylogenetic analysis of the origin and spread of mcr-1, and emphasize the importance of understanding the movement of mobile elements carrying antibiotic resistance genes across multiple levels of genomic organization.

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Colistin-resistance gene mcr in clinical carbapenem-resistant Enterobacteriaceae strains in China, 2014–2019

Emerging Microbes & Infections ◽

10.1080/22221751.2020.1717380 ◽

2020 ◽

Vol 9 (1) ◽

pp. 237-245 ◽

Cited By ~ 6

Author(s):

Hong Huang ◽

Ning Dong ◽

Lingbin Shu ◽

Jiayue Lu ◽

Qiaoling Sun ◽

...

Keyword(s):

Resistance Gene ◽

Colistin Resistance ◽

Carbapenem Resistant ◽

Carbapenem Resistant Enterobacteriaceae

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Detection of themcr-1Colistin Resistance Gene in Carbapenem-Resistant Enterobacteriaceae from Different Hospitals in China

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00440-16 ◽

2016 ◽

Vol 60 (8) ◽

pp. 5033-5035 ◽

Cited By ~ 60

Author(s):

Hua Yu ◽

Fen Qu ◽

Bin Shan ◽

Bin Huang ◽

Wei Jia ◽

...

Keyword(s):

Escherichia Coli ◽

Global Health ◽

Resistance Gene ◽

Clinical Isolates ◽

Chromosomal Integration ◽

Colistin Resistance ◽

Content Type ◽

E Coli ◽

Carbapenem Resistant ◽

Carbapenem Resistant Enterobacteriaceae

ABSTRACTThe spread of the plasmid-mediated colistin resistance gene,mcr-1, into carbapenem-resistantEnterobacteriaceae(CRE) clinical isolates poses a significant threat to global health. Here we report the identification of threemcr-1-harboring carbapenem-resistantEscherichia colistrains, collected from three patients in two provinces in China. Our results show thatmcr-1-harboring CRE strains have started to spread in different hospitals in China. In addition, this report presents the first description of chromosomal integration ofmcr-1into a carbapenem-resistantE. colistrain.

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A Bibliometric Meta-Analysis of Colistin Resistance in Klebsiella pneumoniae

Diseases ◽

10.3390/diseases9020044 ◽

2021 ◽

Vol 9 (2) ◽

pp. 44

Author(s):

Ozioma Forstinus Nwabor ◽

Pawarisa Terbtothakun ◽

Supayang P. Voravuthikunchai ◽

Sarunyou Chusri

Keyword(s):

Klebsiella Pneumoniae ◽

Research Collaboration ◽

Research Output ◽

Meta Analysis ◽

Research Articles ◽

Colistin Resistance ◽

Carbapenem Resistant ◽

The Usa ◽

Carbapenem Resistant Enterobacteriaceae ◽

Linkage Strength

Colistin is a last resort antibiotic medication for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae. In recent years, various mechanisms have been reported to mediate colistin resistance in K. pneumoniae. This study reports a bibliometric analysis of published articles retrieved from the Scopus database relating to colistin resistance in K. pneumoniae. The research trends in colistin resistance and mechanisms of resistance were considered. A total of 1819 research articles published between 1995 and 2019 were retrieved, and the results indicated that 50.19% of the documents were published within 2017–2019. The USA had the highest participation with 340 (14.31%) articles and 14087 (17.61%) citations. Classification based on the WHO global epidemiological regions showed that the European Region contributed 42% of the articles while the American Region contributed 21%. The result further indicated that 45 countries had published at least 10 documents with strong international collaborations amounting to 272 links and a total linkage strength of 735. A total of 2282 keywords were retrieved; however, 57 keywords had ≥15 occurrences with 764 links and a total linkage strength of 2388. Furthermore, mcr-1, colistin resistance, NDM, mgrB, ceftazidime-avibactam, MDR, combination therapy, and carbapenem-resistant Enterobacteriaceae were the trending keywords. Concerning funders, the USA National Institute of Health funded 9.1% of the total research articles, topping the list. The analysis indicated poor research output, collaboration, and funding from Africa and South-East Asia and demands for improvement in international research collaboration.

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Emergence of Colistin Resistance Gene mcr-1 in Cronobacter sakazakii Producing NDM-9 and in Escherichia coli from the Same Animal

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01444-16 ◽

2016 ◽

Vol 61 (2) ◽

Cited By ~ 29

Author(s):

Bao-Tao Liu ◽

Feng-Jing Song ◽

Ming Zou ◽

Zhi-Hui Hao ◽

Hu Shan

Keyword(s):

Escherichia Coli ◽

Resistance Gene ◽

Resistance Genes ◽

Cronobacter Sakazakii ◽

Colistin Resistance ◽

Content Type ◽

E Coli ◽

Carbapenem Resistant

ABSTRACT We report the presence of mcr-1 in Escherichia coli and carbapenem-resistant Cronobacter sakazakii from the same diseased chicken. The mcr-1 gene linked with ISApl1 was located on two different IncI2 plasmids, including one multidrug plasmid in E. coli, whereas fosA3-bla NDM-9 was on an IncB/O plasmid in C. sakazakii. The development of the fosA3-bla NDM-9 resistance region was mediated by IS26. The colocation of mcr-1 or bla NDM-9 with other resistance genes will accelerate the dissemination of the two genes.

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IS26 mediate the acquisition of tigecycline resistance gene cluster tmexCD1-toprJ1 by IncHI1B-FIB plasmids in Klebsiella pneumoniae and Klebsiella quasipneumoniae from food market sewage

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02178-20 ◽

2020 ◽

Author(s):

Miao Wan ◽

Xun Gao ◽

Luchao Lv ◽

Zhongpeng Cai ◽

Jian-Hua Liu

Keyword(s):

Klebsiella Pneumoniae ◽

Gene Cluster ◽

Resistance Gene ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Resistance Gene Cluster ◽

Carbapenem Resistant ◽

Food Market ◽

Carbapenem Resistant Enterobacteriaceae

Tigecycline and colistin are considered 20 as the final options for the treatment of infections caused by multidrug-resistant (MDR) gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae (1).…

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Detection of mobile colistin resistance gene mcr-9 in carbapenem-resistant Klebsiella pneumoniae strains of human origin in Europe

Journal of Infection ◽

10.1016/j.jinf.2019.12.016 ◽

2020 ◽

Vol 80 (5) ◽

pp. 578-606 ◽

Cited By ~ 13

Author(s):

Yanan Wang ◽

Fei Liu ◽

Yongfei Hu ◽

Gaiping Zhang ◽

Baoli Zhu ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Resistance Gene ◽

Human Origin ◽

Colistin Resistance ◽

Carbapenem Resistant

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Silent spread of mobile colistin resistance gene mcr-9.1 on IncHI2 ‘superplasmids’ in clinical carbapenem-resistant Enterobacterales

Clinical Microbiology and Infection ◽

10.1016/j.cmi.2021.04.020 ◽

2021 ◽

Author(s):

Nenad Macesic ◽

Luke V. Blakeway ◽

James D. Stewart ◽

Jane Hawkey ◽

Kelly L. Wyres ◽

...

Keyword(s):

Resistance Gene ◽

Colistin Resistance ◽

Carbapenem Resistant

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First Report of the mcr-1 colistin Resistance Gene Identified in Escherichia coli Isolated from a Clinical Sample in Naples in 2020

10.21203/rs.3.rs-135159/v1 ◽

2020 ◽

Author(s):

BIAGIO SANTELLA ◽

CARLA ZANNELLA ◽

CHIARA DEL VECCHIO ◽

ANNALISA CHIANESE ◽

VERONICA FOLLIERO ◽

...

Keyword(s):

Escherichia Coli ◽

Resistance Gene ◽

Clinical Sample ◽

Resistance Mechanism ◽

Multidrug Resistant ◽

Health Concern ◽

Colistin Resistance ◽

Gram Negative ◽

E Coli ◽

Carbapenem Resistant

Abstract Background: The emergence of a novel plasmid-mediated colistin resistance mechanism, encoded by the mcr-1 gene, represents a major public health concern. The mechanism of resistance to colistin, mediated by plasmids, is a serious problem, both for its ability to be transferred to other species, and for infections caused by carbapenem-resistant Gram-negative, in which colistin is used as an antimicrobial drug of last line for the treatment of these infections. The present study highlights the first isolation and genetic evaluation of detecting plasmid-mediated resistance to colistin in a multidrug-resistant (MDR) Escherichia coli (E. coli) isolated from a clinical sample in the metropolitan city of Naples, Italy. Results: Colistin-resistant E. coli isolate was identified in August 2020 from the blood culture of a male patient with multiple comorbidities. The minimum inhibitory concentration (MIC) of colistin was 8 mg/L. In addition to colistin, the isolate was resistant to third-generation cephalosporins (cefotaxime and ceftazidime), penicillin (amoxicillin and piperacillin), aminoglycosides (gentamicin and tobramycin), and fluoroquinolones (ciprofloxacin and levofloxacin). However, it showed susceptibility to carbapenems (ertapenem, imipenem, and meropenem), tetracyclines (tigecycline), and piperacillin-tazobactam. The results of the PCR confirmed the presence of the mcr-1 resistance gene. Conclusion: This study confirms the presence of resistance to colistin mediated by the mcr-1 gene in a clinical isolate of E. coli. Although resistance to colistin caused by the mcr-1 gene is not common in our region, it should not be ignored. Therefore, further surveillance studies are recommended to monitor the spread of plasmid-mediated colistin resistance genes in Gram-negative MDR bacteria.

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