MCR-1 Confers Cross-Resistance to Bacitracin, a Widely Used In-Feed Antibiotic

ABSTRACT Extensive use of colistin in food animals is deemed a major driving force for the emergence and transmission of mcr-1. However, a non-colistin usage factor(s) contributing to mobile colistin resistance may also exist in animal production systems. Given that polymyxin, a bacterium-derived peptide antibiotic, has been successfully used as a surrogate to study bacterial resistance to antimicrobial peptides (AMPs), acquisition of MCR-1 may confer cross-resistance to the unrelated AMPs implicated in practical applications. To test this, we first constructed Escherichia coli recombinant strains differing only in the presence or absence of functional MCR-1. Among diverse tested AMPs, MCR-1 was observed to confer cross-resistance to bacitracin, an in-feed antibiotic widely used in animal industry. The significantly (2-fold) increased bacitracin MIC was confirmed by using different bacitracin products, broth media, and laboratory host strains for susceptibility tests. Subsequently, an original mcr-1 gene-bearing plasmid, pSLy21, was conjugatively transferred to eight clinical E. coli recipient strains isolated from diarrheic pigs, which also led to significantly increased MICs of both colistin (4-fold to 8-fold) and bacitracin (2-fold). Growth curve examination further demonstrated that MCR-1 provides a growth advantage to various E. coli strains in the presence of bacitracin. Given that bacitracin, a feed additive displaying low absorption in the intestine, can be used in food animals with no withdrawal required, imprudent use of bacitracin in food animals may serve as a risk factor to enhance the ecological fitness of MCR-1-positive E. coli strains, consequently facilitating the persistence and transmission of plasmid-mediated colistin resistance in agricultural ecosystem. IMPORTANCE Polymyxins (e.g., colistin) are the drugs of last resort to treat multidrug-resistant infections in humans. To control mobile colistin resistance, there is a worldwide trend to limit colistin use in animal production. However, simply limiting colistin use in animal production may still not effectively mitigate colistin resistance due to an overlooked non-colistin usage factor(s). Using controlled systems, in this study, we observed that MCR-1 confers cross-resistance to bacitracin, a popular in-feed antibiotic used in food animals. Thus, imprudent and extensive usage of bacitracin in food animals may serve as a non-colistin usage risk factor for the transmissible colistin resistance. Further comprehensive in vitro and in vivo studies are highly warranted to generate science-based information for risk assessment and risk management of colistin resistance, consequently facilitating the development of proactive and effective strategies to mitigate colistin resistance in animal production system and protect public health.

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Plasmid-mediated colistin resistance in animals: current status and future directions

Animal Health Research Reviews ◽

10.1017/s1466252317000111 ◽

2017 ◽

Vol 18 (2) ◽

pp. 136-152 ◽

Cited By ~ 14

Author(s):

Jian Sun ◽

Ximin Zeng ◽

Xing-Ping Li ◽

Xiao-Ping Liao ◽

Ya-Hong Liu ◽

...

Keyword(s):

Production Systems ◽

Multidrug Resistant ◽

Animal Production ◽

Health Concern ◽

Current Status ◽

Peptide Antibiotic ◽

Colistin Resistance ◽

Significant Public Health ◽

The Usa ◽

Food Animals

AbstractColistin, a peptide antibiotic belonging to the polymyxin family, is one of the last effective drugs for the treatment of multidrug resistant Gram-negative infections. Recent discovery of a novel mobile colistin resistance gene,mcr-1, from people and food animals has caused a significant public health concern and drawn worldwide attention. Extensive usage of colistin in food animals has been proposed as a major driving force for the emergence and transmission ofmcr-1; thus, there is a worldwide trend to limit colistin usage in animal production. However, despite lack of colistin usage in food animals in the USA,mcr-1-positiveEscherichia coliisolates were still isolated from swine. In this paper, we provided an overview of colistin usage and epidemiology ofmcr-1in food animals, and summarized the current status of mechanistic and evolutionary studies of the plasmid-mediated colistin resistance. Based on published information, we further discussed several non-colistin usage risk factors that may contribute to the persistence, transmission, and emergence of colistin resistance in an animal production system. Filling the knowledge gaps identified in this review is critical for risk assessment and risk management of colistin resistance, which will facilitate proactive and effective strategies to mitigate colistin resistance in future animal production systems.

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Activity of Ceftazidime-Avibactam against Fluoroquinolone-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05136-14 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3059-3065 ◽

Cited By ~ 14

Author(s):

C. Pitart ◽

F. Marco ◽

T. A. Keating ◽

W. W. Nichols ◽

J. Vila

Keyword(s):

Pseudomonas Aeruginosa ◽

Resistant Mutant ◽

Fluoroquinolone Resistance ◽

Cross Resistance ◽

Content Type ◽

E Coli ◽

Microdilution Method ◽

Broth Microdilution Method ◽

The Impact

ABSTRACTCeftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200Enterobacteriaceaeand 25Pseudomonas aeruginosastrains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistantEnterobacteriaceaestrains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBLEscherichia coli(MIC90of 0.25 mg/liter), ESBLKlebsiella pneumoniae(MIC90of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90of 1 mg/liter), non-ESBLE. coli(MIC90of ≤0.125 mg/liter), non-ESBLK. pneumoniae(MIC90of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistantP. aeruginosastrains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtainedin vitrofrom two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains ofEnterobacteriaceaeandP. aeruginosawere ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affectEnterobacteriaceaeandP. aeruginosasusceptibility to ceftazidime-avibactam; that is, there is no cross-resistance.

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An Improved Medium for Colistin Susceptibility Testing

Journal of Clinical Microbiology ◽

10.1128/jcm.01950-17 ◽

2018 ◽

Vol 56 (5) ◽

Cited By ~ 10

Author(s):

Konrad Gwozdzinski ◽

Saina Azarderakhsh ◽

Can Imirzalioglu ◽

Linda Falgenhauer ◽

Trinad Chakraborty

Keyword(s):

Susceptibility Testing ◽

Acquired Resistance ◽

Multidrug Resistant ◽

Colistin Resistance ◽

Reliable Determination ◽

Content Type ◽

E Coli ◽

Resistant Species ◽

Mueller Hinton ◽

Serovar Typhimurium

ABSTRACTThe plasmid-located colistin resistance genemcr-1confers low-level resistance to colistin, a last-line antibiotic against multidrug-resistant Gram-negative bacteria. Current CLSI-EUCAST recommendations require the use of a broth microdilution (BMD) method with cation-adjusted Mueller-Hinton (CA-MH) medium for colistin susceptibility testing, but approximately 15% of all MCR-1 producers are classified as sensitive in that broth. Here we report on an improved calcium-enhanced Mueller-Hinton (CE-MH) medium that permits simple and reliable determination ofmcr-1-containingEnterobacteriaceae. Colistin susceptibility testing was performed for 50mcr-1-containingEscherichia coliandKlebsiella pneumoniaeisolates, 7 intrinsically polymyxin-resistant species,K. pneumoniaeandE. coliisolates with acquired resistance to polymyxins due tomgrBandpmrBmutations, respectively, and 32mcr-1-negative, colistin-susceptible isolates ofAcinetobacter baumannii,Citrobacter freundii,Enterobacter cloacae,E. coli,K. pneumoniae, andSalmonella entericaserovar Typhimurium. A comparison of the colistin MICs determined in CA-MH medium and those obtained in CE-MH medium was performed using both the BMD and strip-based susceptibility test formats. We validated the data using an isogenic IncX4 plasmid lackingmcr-1. Use of the CE-MH broth provides clear separation between resistant and susceptible isolates in both BMD and gradient diffusion assays; this is true for bothmcr-1-containingEnterobacteriaceaeisolates and those exhibiting either intrinsic or acquired colistin resistance. CE-MH medium is simple to prepare and overcomes current problems associated with BMD and strip-based colistin susceptibility testing, and use of the medium is easy to implement in routine diagnostic laboratories, even in resource-poor settings.

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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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Phenotypic Detection of Plasmid-Mediated Colistin Resistance in Enterobacteriaceae

Journal of Clinical Microbiology ◽

10.1128/jcm.01555-19 ◽

2019 ◽

Vol 58 (3) ◽

Cited By ~ 3

Author(s):

Edgar Gonzales Escalante ◽

Katherine Yauri Condor ◽

Jose A. Di Conza ◽

Gabriel O. Gutkind

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Serratia Marcescens ◽

Bacterial Growth ◽

Screening Test ◽

Colistin Resistance ◽

Content Type ◽

E Coli

ABSTRACT The aim of this work was to evaluate an easy-to-perform assay based upon inhibition of mobile colistin resistance (MCR) activity by EDTA. We included 92 nonrelated isolates of Enterobacteriaceae (74 Escherichia coli, 17 Klebsiella pneumoniae, and 1 Serratia marcescens). Our proposed method is based on a modification of the colistin agar-spot screening test (CAST), a plate containing 3 μg/ml colistin, by adding an extra plate of colistin agar-spot supplemented with EDTA (eCAST). Bacterial growth was evaluated after 24 h of incubation at 35°C. All the colistin-resistant isolates showed development on the CAST plates. Colistin-resistant K. pneumoniae without mcr-1 and S. marcescens also grew on the eCAST plates. In contrast, colistin-resistant MCR-producing E. coli was not able to grow in eCAST plates. The combined CAST/eCAST test could provide a simple and easy-to-perform method to differentiate MCR-producing Enterobacteriaceae from those in which colistin resistance is mediated by chromosomal mechanisms.

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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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Structural Modification of Lipopolysaccharide Conferred by mcr-1 in Gram-Negative ESKAPE Pathogens

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00580-17 ◽

2017 ◽

Vol 61 (6) ◽

Cited By ~ 49

Author(s):

Yi-Yun Liu ◽

Courtney E. Chandler ◽

Lisa M. Leung ◽

Christi L. McElheny ◽

Roberta T. Mettus ◽

...

Keyword(s):

Structural Changes ◽

Lipid A ◽

Colistin Resistance ◽

Gram Negative ◽

Content Type ◽

Clinical Strains ◽

E Coli ◽

The Family ◽

Phosphoethanolamine Transferases ◽

Eskape Pathogens

ABSTRACT mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceae. mcr-1 encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-acylated lipid A in E. coli. Here, we investigated the effects of mcr-1 on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens, which are often treated clinically by colistin. The effects of mcr-1 on colistin resistance were determined using MIC assays of laboratory and clinical strains of E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa. Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of mcr-1 led to colistin resistance in E. coli, K. pneumoniae, and A. baumannii but only moderately reduced susceptibility in P. aeruginosa. Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of mcr-1 expression among ESKAPE pathogens, especially in K. pneumoniae and A. baumannii. Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of mcr-1 or plasmid-mediated phosphoethanolamine transferases in general.

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The Plasmid-Mediated Kluyvera-Like arnBCADTEF Operon Confers Colistin (Hetero)Resistance to Escherichia coli

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00091-21 ◽

2021 ◽

Vol 65 (5) ◽

Author(s):

Alejandro Gallardo ◽

María-Rocío Iglesias ◽

María Ugarte-Ruiz ◽

Marta Hernández ◽

Pedro Miguela-Villoldo ◽

...

Keyword(s):

Escherichia Coli ◽

Genomic Sequencing ◽

Colistin Resistance ◽

Extra Copy ◽

Main Determinant ◽

Content Type ◽

E Coli ◽

Constitutive Activation ◽

Resistance Determinants ◽

Kluyvera Ascorbata

ABSTRACT The use of colistin as a last-resort antimicrobial is compromised by the emergence of resistant enterobacteria with acquired determinants like mcr genes, mutations that activate the PmrAB system, or still unknown mechanisms. This work analyzed 74 Escherichia coli isolates from healthy swine, turkey, or bovine, characterizing their colistin resistance determinants. The mcr-1 gene, detected in 69 isolates, was the main determinant found, among which 45% carried this gene on highly mobile plasmids, followed by 4 strains lacking previously known resistance determinants or 2 with mcr-4 (1 in addition to mcr-1), whose phenotypes were not transferred by conjugation. Although a fraction of isolates carrying mcr-1 or mcr-4 genes also presented missense polymorphisms in pmrA or pmrB, constitutive activation of PmrAB was not detected, in contrast to strains with mutations that confer colistin resistance. The expression of mcr genes negatively controls the transcription of the arnBCADTEF operon itself, a downregulation that was also observed in the four isolates lacking known resistance determinants, with three of them sharing the same macrorestriction and plasmid profiles. Genomic sequencing of one of these strains, isolated from a bovine in 2015, revealed an IncFII plasmid of 62.1 kb carrying an extra copy of the arnBCADTEF operon closely related to Kluyvera ascorbata homologs. This element, called pArnT1, was cured by ethidium bromide, and the cells lost resistance to colistin in parallel. Furthermore, a susceptible E. coli strain acquired heteroresistance after transformation with pArnT1 or pBAD24 carrying the Kluyvera-like arnBCADTEF operon, revealing it as a new colistin resistance determinant.

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Acquisition of mcr-1 and Cocarriage of Virulence Genes in Avian Pathogenic Escherichia coli Isolates from Municipal Wastewater Influents in Japan

Applied and Environmental Microbiology ◽

10.1128/aem.01661-19 ◽

2019 ◽

Vol 85 (22) ◽

Cited By ~ 6

Author(s):

Wataru Hayashi ◽

Hayato Tanaka ◽

Yui Taniguchi ◽

Masaki Iimura ◽

Eiji Soga ◽

...

Keyword(s):

Escherichia Coli ◽

Virulence Genes ◽

Sequence Similarity ◽

Multidrug Resistant ◽

Common Source ◽

High Sequence Similarity ◽

Content Type ◽

E Coli ◽

Query Coverage ◽

Food Animals

ABSTRACT This study focused on the detection of the plasmid-mediated mcr colistin resistance gene in Escherichia coli isolates from wastewater treatment plants (WWTPs). Seven influent samples were collected from three WWTPs in Nagano Prefecture, Japan, during August and December 2018. Colistin-resistant E. coli isolates were selected on colistin-supplemented CHROMagar ECC plates. mcr-1-positive isolates were subjected to whole-genome sequencing (WGS) analysis. From six influent samples, seven mcr-1-positive but extended-spectrum β-lactamase (ESBL)-negative isolates belonging to different genetic lineages, namely, B2-O25:H4-ST131-fimH22, B2-O2:H1-ST135-fimH2, B1-O8:H9-ST764-fimH32, B1-O23:H16-ST453-fimH31, A-O81:H27-ST10-fimH54, A-O16:H5-ST871-fimH25, and F-O11:H6-ST457-fimH145, were detected. The MICs of colistin for these isolates ranged from 4 to 16 mg/liter. The mcr-1 genes were located on plasmids belonging to IncX4 and IncI2 in five and two isolates, respectively. Four IncX4 plasmids with the same size (33,309 bp) showed high sequence similarity (4 single-nucleotide variations). The remaining one IncX4 plasmid, with a size of 33,858 bp, carried the mcr-1 gene with the single synonymous nucleic substitution T27C. Two IncI2 plasmids with sizes of 60,710 bp and 60,733 bp had high sequence similarity (99.9% identity; 100% query coverage). Two of five isolates carrying IncX4 plasmids and both of the isolates carrying IncI2 plasmids harbored ColV plasmids carrying virulence-associated genes of avian pathogenic E. coli (APEC). In addition, another isolate of the B2-O25:H4-ST131-fimH22 lineage had those APEC-associated virulence genes on its chromosome. In conclusion, mcr-1-positive E. coli environmental isolates were mostly characterized as positive for APEC-associated virulence genes. The copresence of those genes may suggest the existence of a common source in animals and/or their associated environments. IMPORTANCE Colistin is considered a last-line therapeutic option in severe infections due to multidrug-resistant Gram-negative bacteria, in particular carbapenemase-producing Enterobacteriaceae and multidrug-resistant Acinetobacter baumannii. An increasing prevalence of mcr genes in diverse Enterobacteriaceae species, mainly Escherichia coli and Klebsiella pneumoniae from humans and food animals, has become a significant concern to public health all over the world. In Japan, mcr genes have so far been detected in food animals, raw meat, wastewater, and human clinical samples. This study reports the copresence of mcr-1 and avian pathogenic E. coli (APEC)-associated virulence genes in five of seven E. coli isolates recovered from aquatic environments in Japan. Our study highlights the importance and urgency of action to reduce environmental contamination by mcr genes that may likely occur due to exposure to untreated wastewater through combined sewer overflow by recent unusual weather.

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Discovery ofmcr-1-Mediated Colistin Resistance in a Highly VirulentEscherichia coliLineage

mSphere ◽

10.1128/msphere.00486-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 12

Author(s):

Brian M. Forde ◽

Hosam M. Zowawi ◽

Patrick N. A. Harris ◽

Leah Roberts ◽

Emad Ibrahim ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Neonatal Meningitis ◽

Colistin Resistance ◽

Content Type ◽

E Coli ◽

Virulence Potential ◽

High Virulence

ABSTRACTResistance to last-line polymyxins mediated by the plasmid-borne mobile colistin resistance gene (mcr-1) represents a new threat to global human health. Here we present the complete genome sequence of anmcr-1-positive multidrug-resistantEscherichia colistrain (MS8345). We show that MS8345 belongs to serotype O2:K1:H4, has a large 241,164-bp IncHI2 plasmid that carries 15 other antibiotic resistance genes (including the extended-spectrum β-lactamaseblaCTX-M-1) and 3 putative multidrug efflux systems, and contains 14 chromosomally encoded antibiotic resistance genes. MS8345 also carries a large ColV-like virulence plasmid that has been associated withE. colibacteremia. Whole-genome phylogeny revealed that MS8345 clusters within a discrete clade in the sequence type 95 (ST95) lineage, and MS8345 is very closely related to the highly virulent O45:K1:H4 clone associated with neonatal meningitis. Overall, the acquisition of a plasmid carrying resistance to colistin and multiple other antibiotics in this virulentE. colilineage is concerning and might herald an era where the empirical treatment of ST95 infections becomes increasingly more difficult.IMPORTANCEEscherichia coliST95 is a globally disseminated clone frequently associated with bloodstream infections and neonatal meningitis. However, the ST95 lineage is defined by low levels of drug resistance amongst clinical isolates, which normally provides for uncomplicated treatment options. Here, we provide the first detailed genomic analysis of anE. coliST95 isolate that has both high virulence potential and resistance to multiple antibiotics. Using the genome, we predicted its virulence and antibiotic resistance mechanisms, which include resistance to last-line antibiotics mediated by the plasmid-bornemcr-1gene. Finding an ST95 isolate resistant to nearly all antibiotics that also has a high virulence potential is of major clinical importance and underscores the need to monitor new and emerging trends in antibiotic resistance development in this important global lineage.

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