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

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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Heterogeneous and Flexible Transmission ofmcr-1in Hospital-AssociatedEscherichia coli

mBio ◽

10.1128/mbio.00943-18 ◽

2018 ◽

Vol 9 (4) ◽

Cited By ~ 23

Author(s):

Yingbo Shen ◽

Zuowei Wu ◽

Yang Wang ◽

Rong Zhang ◽

Hong-Wei Zhou ◽

...

Keyword(s):

Escherichia Coli ◽

Genomic Analysis ◽

Multidrug Resistant ◽

Fluoroquinolone Resistance ◽

Gram Negative Bacteria ◽

Colistin Resistance ◽

Gram Negative ◽

Content Type ◽

E Coli ◽

Genes Encoding

ABSTRACTThe recent emergence of a transferable colistin resistance mechanism, MCR-1, has gained global attention because of its threat to clinical treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, the possible transmission route ofmcr-1amongEnterobacteriaceaespecies in clinical settings is largely unknown. Here, we present a comprehensive genomic analysis ofEscherichia coliisolates collected in a hospital in Hangzhou, China. We found thatmcr-1-carrying isolates from clinical infections and feces of inpatients and healthy volunteers were genetically diverse and were not closely related phylogenetically, suggesting that clonal expansion is not involved in the spread ofmcr-1. Themcr-1gene was found on either chromosomes or plasmids, but in most of theE. coliisolates,mcr-1was carried on plasmids. The genetic context of the plasmids showed considerable diversity as evidenced by the different functional insertion sequence (IS) elements, toxin-antitoxin (TA) systems, heavy metal resistance determinants, and Rep proteins of broad-host-range plasmids. Additionally, the genomic analysis revealed nosocomial transmission ofmcr-1and the coexistence ofmcr-1with other genes encoding β-lactamases and fluoroquinolone resistance in theE. coliisolates. These findings indicate thatmcr-1is heterogeneously disseminated in both commensal and pathogenic strains ofE. coli, suggest the high flexibility of this gene in its association with diverse genetic backgrounds of the hosts, and provide new insights into the genome epidemiology ofmcr-1among hospital-associatedE. colistrains.IMPORTANCEColistin represents one of the very few available drugs for treating infections caused by extensively multidrug-resistant Gram-negative bacteria. The recently emergentmcr-1colistin resistance gene threatens the clinical utility of colistin and has gained global attention. Howmcr-1spreads in hospital settings remains unknown and was investigated by whole-genome sequencing ofmcr-1-carryingEscherichia coliin this study. The findings revealed extraordinary flexibility ofmcr-1in its spread among genetically diverseE. colihosts and plasmids, nosocomial transmission ofmcr-1-carryingE. coli, and the continuous emergence of novel Inc types of plasmids carryingmcr-1and newmcr-1variants. Additionally,mcr-1was found to be frequently associated with other genes encoding β-lactams and fluoroquinolone resistance. These findings provide important information on the transmission and epidemiology ofmcr-1and are of significant public health importance as the information is expected to facilitate the control of this significant antibiotic resistance threat.

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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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Colistin-resistant Escherichia coli clinical isolate harbouring the mcr-1 gene in Ecuador

Epidemiology and Infection ◽

10.1017/s0950268816001369 ◽

2016 ◽

Vol 144 (14) ◽

pp. 2967-2970 ◽

Cited By ~ 27

Author(s):

D. ORTEGA-PAREDES ◽

P. BARBA ◽

J. ZURITA

Keyword(s):

Escherichia Coli ◽

Minimum Inhibitory Concentration ◽

Clinical Isolate ◽

Inhibitory Concentration ◽

Resistance Mechanism ◽

Sequence Type ◽

Colistin Resistance ◽

Gram Negative ◽

E Coli ◽

Commensal Strain

SUMMARYColistin resistance mediated by the mcr-1 gene has been reported worldwide, but to date not from the Andean region, South America. We report the first clinical isolate of Escherichia coli harbouring the mcr-1 gene in Ecuador. The strain was isolated from peritoneal fluid from a 14-year-old male with acute appendicitis, and subjected to molecular analysis. The minimum inhibitory concentration of colistin for the strain was 8 mg/ml and it was susceptible to carbapenems but resistant to tigecycline. The strain harboured mcr-1 and blaCTX-M-55 genes and was of sequence type 609. The recognition of an apparently commensal strain of E. coli harbouring mcr-1 serves as an alert to the presence in the region of this recently described resistance mechanism to one of the last line of drugs available for the treatment of multi-resistant Gram-negative infections.

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Identification of a novel plasmid-mediated colistin-resistance gene, mcr-2, in Escherichia coli, Belgium, June 2016

Eurosurveillance ◽

10.2807/1560-7917.es.2016.21.27.30280 ◽

2016 ◽

Vol 21 (27) ◽

Cited By ~ 382

Author(s):

Basil Britto Xavier ◽

Christine Lammens ◽

Rohit Ruhal ◽

Samir Kumar-Singh ◽

Patrick Butaye ◽

...

Keyword(s):

Escherichia Coli ◽

Resistance Gene ◽

Epidemiological Surveillance ◽

Nucleotide Identity ◽

Colistin Resistance ◽

Gram Negative ◽

E Coli ◽

Data Call

We identified a novel plasmid-mediated colistin-resistance gene in porcine and bovine colistin-resistant Escherichia coli that did not contain mcr-1. The gene, termed mcr-2, a 1,617 bp phosphoethanolamine transferase harboured on an IncX4 plasmid, has 76.7% nucleotide identity to mcr-1. Prevalence of mcr-2 in porcine colistin-resistant E. coli (11/53) in Belgium was higher than that of mcr-1 (7/53). These data call for an immediate introduction of mcr-2 screening in ongoing molecular epidemiological surveillance of colistin-resistant Gram-negative pathogens.

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Emerging Opportunity and Destiny of mcr-1 - and tet (X4)-Coharboring Plasmids in Escherichia coli

Microbiology Spectrum ◽

10.1128/spectrum.01520-21 ◽

2021 ◽

Author(s):

Xiaoyu Lu ◽

Xia Xiao ◽

Yuan Liu ◽

Ruichao Li ◽

Zhiqiang Wang

Keyword(s):

Escherichia Coli ◽

Human Health ◽

Resistance Gene ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Colistin Resistance ◽

Gram Negative

Tigecycline and colistin are used as last-resort therapies to treat infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, the emergence of the plasmid-mediated tigecycline resistance gene tet (X4) and the plasmid-mediated colistin resistance gene mcr-1 represents a significant threat to human health.

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Plasmid Mediated mcr-1.1 Colistin-Resistance in Clinical Extraintestinal Escherichia coli Strains Isolated in Poland

Frontiers in Microbiology ◽

10.3389/fmicb.2021.547020 ◽

2021 ◽

Vol 12 ◽

Author(s):

Piotr Majewski ◽

Anna Gutowska ◽

David G. E. Smith ◽

Tomasz Hauschild ◽

Paulina Majewska ◽

...

Keyword(s):

Escherichia Coli ◽

Bacterial Pathogens ◽

Multidrug Resistant ◽

Modern Medicine ◽

University Hospital ◽

Great Effort ◽

Colistin Resistance ◽

Livestock Farming ◽

Gram Negative ◽

E Coli

Objectives: The growing incidence of multidrug-resistant (MDR) bacteria is an inexorable and fatal challenge in modern medicine. Colistin is a cationic polypeptide considered a “last-resort” antimicrobial for treating infections caused by MDR Gram-negative bacterial pathogens. Plasmid-borne mcr colistin resistance emerged recently, and could potentially lead to essentially untreatable infections, particularly in hospital and veterinary (livestock farming) settings. In this study, we sought to establish the molecular basis of colistin-resistance in six extraintestinal Escherichia coli strains.Methods: Molecular investigation of colistin-resistance was performed in six extraintestinal E. coli strains isolated from patients hospitalized in Medical University Hospital, Bialystok, Poland. Complete structures of bacterial chromosomes and plasmids were recovered with use of both short- and long-read sequencing technologies and Unicycler hybrid assembly. Moreover, an electrotransformation assay was performed in order to confirm IncX4 plasmid influence on colistin-resistance phenotype in clinical E. coli strains.Results: Here we report on the emergence of six mcr-1.1-producing extraintestinal E. coli isolates with a number of virulence factors. Mobile pEtN transferase-encoding gene, mcr-1.1, has been proved to be encoded within a type IV secretion system (T4SS)-containing 33.3 kbp IncX4 plasmid pMUB-MCR, next to the PAP2-like membrane-associated lipid phosphatase gene.Conclusion: IncX4 mcr-containing plasmids are reported as increasingly disseminated among E. coli isolates, making it an “epidemic” plasmid, responsible for (i) dissemination of colistin-resistance determinants between different E. coli clones, and (ii) circulation between environmental, industrial, and clinical settings. Great effort needs to be taken to avoid further dissemination of plasmid-mediated colistin resistance among clinically relevant Gram-negative bacterial pathogens.

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

10.21203/rs.3.rs-285784/v1 ◽

2021 ◽

Author(s):

Yi Li ◽

Wenjuan Yan ◽

Qi Zhang ◽

Nan Jing ◽

Youhua Yuan ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Ethylenediaminetetraacetic Acid ◽

Multidrug Resistant ◽

Resistance Rate ◽

Henan Province ◽

Close Monitoring ◽

Colistin Resistance ◽

E Coli ◽

Carbapenem Resistant

Abstract 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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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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Insights into the Environmental Resistance Gene Pool from the Genome Sequence of the Multidrug-Resistant Environmental Isolate Escherichia coli SMS-3-5

Journal of Bacteriology ◽

10.1128/jb.00661-08 ◽

2008 ◽

Vol 190 (20) ◽

pp. 6779-6794 ◽

Cited By ~ 63

Author(s):

W. Florian Fricke ◽

Meredith S. Wright ◽

Angela H. Lindell ◽

Derek M. Harkins ◽

Craig Baker-Austin ◽

...

Keyword(s):

Escherichia Coli ◽

Antimicrobial Resistance ◽

Resistance Gene ◽

Gene Pool ◽

Multidrug Resistant ◽

Health Concern ◽

Transport Systems ◽

Global Public Health ◽

E Coli ◽

The Impact

ABSTRACT The increasing occurrence of multidrug-resistant pathogens of clinical and agricultural importance is a global public health concern. While antimicrobial use in human and veterinary medicine is known to contribute to the dissemination of antimicrobial resistance, the impact of microbial communities and mobile resistance genes from the environment in this process is not well understood. Isolated from an industrially polluted aquatic environment, Escherichia coli SMS-3-5 is resistant to a record number of antimicrobial compounds from all major classes, including two front-line fluoroquinolones (ciprofloxacin and moxifloxacin), and in many cases at record-high concentrations. To gain insights into antimicrobial resistance in environmental bacterial populations, the genome of E. coli SMS-3-5 was sequenced and compared to the genome sequences of other E. coli strains. In addition, selected genetic loci from E. coli SMS-3-5 predicted to be involved in antimicrobial resistance were phenotypically characterized. Using recombinant vector clones from shotgun sequencing libraries, resistance to tetracycline, streptomycin, and sulfonamide/trimethoprim was assigned to a single mosaic region on a 130-kb plasmid (pSMS35_130). The remaining plasmid backbone showed similarity to virulence plasmids from avian-pathogenic E. coli (APEC) strains. Individual resistance gene cassettes from pSMS35_130 are conserved among resistant bacterial isolates from multiple phylogenetic and geographic sources. Resistance to quinolones was assigned to several chromosomal loci, mostly encoding transport systems that are also present in susceptible E. coli isolates. Antimicrobial resistance in E. coli SMS-3-5 is therefore dependent both on determinants acquired from a mobile gene pool that is likely available to clinical and agricultural pathogens, as well, and on specifically adapted multidrug efflux systems. The association of antimicrobial resistance with APEC virulence genes on pSMS35_130 highlights the risk of promoting the spread of virulence through the extensive use of antibiotics.

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Emergence of carbapenem-resistant ST131 Escherichia coli carrying blaOXA-244 in Germany, 2019 to 2020

Eurosurveillance ◽

10.2807/1560-7917.es.2020.25.46.2001815 ◽

2020 ◽

Vol 25 (46) ◽

Author(s):

Sybille Welker ◽

Sébastien Boutin ◽

Thomas Miethke ◽

Klaus Heeg ◽

Dennis Nurjadi

Keyword(s):

Escherichia Coli ◽

Carbapenem Resistance ◽

Health Concern ◽

Gram Negative Bacteria ◽

Public Health Concern ◽

Gram Negative ◽

E Coli ◽

Carbapenem Resistant ◽

South West ◽

Tertiary Hospitals

The dissemination of carbapenem-producing Gram-negative bacteria is a major public health concern. We report the first detection of OXA-244-producing ST131 O16:H5 Escherichia coli in three patients from two tertiary hospitals in the south-west of Germany. OXA-244 is emerging in Europe. Because of detection challenges, OXA-244-producing E. coli may be under-reported. The emergence of carbapenem resistance in a globally circulating high-risk clone, such as ST131 E. coli is of clinical relevance and should be monitored closely.

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