Genetic and Functional Characterization of an MCR-3-Like Enzyme-Producing Escherichia coli Isolate Recovered from Swine in Brazil

Kieffer, Nicolas; Nordmann, Patrice; Moreno, Andréa Micke; Moreno, Luisa Zanolli; Chaby, Richard; Breton, Aude; Tissières, Pierre; Poirel, Laurent

doi:10.1128/aac.00278-18

Cited by 42 publications

(37 citation statements)

References 38 publications

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“…2). This modification corresponded to the addition of a phosphoethanolamine (PEtN) group to lipid A, as previously reported for MCR-1 to MCR-3 producers (27)(28)(29) (Fig. 2).…”

Section: Resultssupporting

confidence: 76%

“…Analysis of the LPS modification. The LPS of E. coli TOP10 (unmodified lipid A), of isolate E. coli 68A (mcr-9 positive) grown in the presence or absence of colistin, of the E. coli(pBAD-mcr-9) clone carrying the mcr-9 gene in the pBAD vector, grown in the presence or absence of L-arabinose, of B. gaviniae, and of the E. coli(pBAD-mcr-3.12) clone carrying the mcr-3.12 gene as a control were analyzed by mass spectrometry (29). Lipid A was extracted using an acetic acid-based procedure as previously described (40,41).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

mcr-9 , an Inducible Gene Encoding an Acquired Phosphoethanolamine Transferase in Escherichia coli, and Its Origin

Kieffer

Royer

Decousser

et al. 2019

Antimicrob Agents Chemother

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146

199

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The plasmid-located mcr-9 gene, encoding a putative phosphoethanolamine transferase, was identified in a colistin-resistant human fecal Escherichia coli strain belonging to a very rare phylogroup, the D-ST69-O15:H6 clone. This MCR-9 protein shares 33% to 65% identity with the other plasmid-encoded MCR-type enzymes identified (MCR-1 to -8) that have been found as sources of acquired resistance to polymyxins in Enterobacteriaceae. Analysis of the lipopolysaccharide of the MCR-9-producing isolate revealed a function similar to that of MCR-1 by adding a phosphoethanolamine group to lipid A and subsequently modifying the structure of the lipopolysaccharide. However, a minor impact on susceptibility to polymyxins was noticed once the mcr-9 gene was cloned and produced in an E. coli K-12-derived strain. Nevertheless, we showed here that subinhibitory concentrations of colistin induced the expression of the mcr-9 gene, leading to increased MIC levels. This inducible expression was mediated by a two-component regulatory system encoded by the qseC and qseB genes located downstream of mcr-9. Genetic analysis showed that the mcr-9 gene was carried by an IncHI2 plasmid. In silico analysis revealed that the plasmid-encoded MCR-9 shared significant amino acid identity (ca. 80%) with the chromosomally encoded MCR-like proteins from Buttiauxella spp. In particular, Buttiauxella gaviniae was found to harbor a gene encoding MCR-BG, sharing 84% identity with MCR-9. That gene was neither expressed nor inducible in its original host, which was fully susceptible to polymyxins. This work showed that mcr genes may circulate silently and remain undetected unless induced by colistin.

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“…2). This modification corresponded to the addition of a phosphoethanolamine (PEtN) group to lipid A, as previously reported for MCR-1 to MCR-3 producers (27)(28)(29) (Fig. 2).…”

Section: Resultssupporting

confidence: 76%

Section: Methodsmentioning

confidence: 99%

mcr-9 , an Inducible Gene Encoding an Acquired Phosphoethanolamine Transferase in Escherichia coli, and Its Origin

Kieffer

Royer

Decousser

et al. 2019

Antimicrob Agents Chemother

Self Cite

146

199

View full text Add to dashboard Cite

show abstract

“…Among them, a single isolate was positive by PCR for the mcr gene. This isolate was also resistant to broad-spectrum cephalosporins, tetracycline, chloramphenicol, florfenicol, nalidixic acid, sulfonamides, sulfamethoxazole-trimethoprim, and kanamycin [89].…”

Section: E Colimentioning

confidence: 99%

“…The isolate had colistin MIC of 4 µg/mL, and biochemical analysis demonstrated that the enzyme acts similarly to MCR-1. The mcr-3.12 gene was located between two insertion sequences belonging to the IS66 and IS30 families embedded into an IncA/C 2 plasmid [89] 6.4. Quinolones Resistance-Qnr In Brazil, the plasmid-mediated fluoroquinolones resistance qnr genes have been reported in samples from animals or animal-derived foods mainly after 2013.…”

Section: Colistin Resistance-mcrmentioning

confidence: 99%

Antimicrobial Resistance in Farm Animals in Brazil: An Update Overview

Rabello

Bonelli

Penna

et al. 2020

Animals

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In animal husbandry, antimicrobial agents have been administered as supplements to increase production over the last 60 years. Large-scale animal production has increased the importance of antibiotic management because it may favor the evolution of antimicrobial resistance and select resistant strains. Brazil is a significant producer and exporter of animal-derived food. Although Brazil is still preparing a national surveillance plan, several changes in legislation and timely programs have been implemented. Thus, Brazilian data on antimicrobial resistance in bacteria associated with animals come from official programs and the scientific community. This review aims to update and discuss the available Brazilian data on this topic, emphasizing legal aspects, incidence, and genetics of the resistance reported by studies published since 2009, focusing on farm animals and derived foods with the most global public health impact. Studies are related to poultry, cattle, and pigs, and mainly concentrate on non-typhoid Salmonella, Escherichia coli, and Staphylococcus aureus. We also describe legal aspects of antimicrobial use in this context; and the current occurrence of genetic elements associated with resistance to beta-lactams, colistin, and fluoroquinolones, among other antimicrobial agents. Data here presented may be useful to provide a better understanding of the Brazilian status on antimicrobial resistance related to farm animals and animal-derived food products.

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“…The entire mcr-3.19 region including the insertion was flanked by eamA and dgkA. These genes encode a metabolite transporter and a diacylglycerol kinase, respectively [12]. The mcr-3.19 genetic environment also had other insertional elements such as ISAs19, ISAs20, IS630, ISKpn15, IS5 and IS3 transposase.…”

Section: Discussionmentioning

confidence: 99%

First hybrid complete genome ofAeromonas veroniireveals chromosome-mediated novel structural variantmcr-3.19from human clinical specimen

Nkd¹,

Dpm²,

Anandan³

et al. 2019

Preprint

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BackgroundRecent findings substantiate the origin of plasmid-mediated colistin resistance gene mcr-3 from Aeromonads. The present study aimed to screen the plasmid-mediated colistin resistance among 30 clinical multidrug resistant (MDR) Aeromonas spp. ResultsThe presence of mcr-1, mcr-2, mcr-3, and mcr-4 were screened by PCR, which revealed mcr-3 in a colistin susceptible isolate (FC951). All other isolates were negative for mcr genes.Sequencing of FC951 revealed that mcr-3 (mcr-3.19) identified was different from previously reported variants and had 95.62 and 95.28% nucleotide similarity with mcr-3.3 and mcr-3.10 gene. A hybrid assembly using IonTorrent and MinION reads revealed structural genetic information of mcr-3.19 with an insertion of ISAs18 within the gene. Due to this, mcr-3.19was non-expressive which makes FC951 susceptible to colistin. Further, in silico sequence and protein structural analysis confirmed the new variant. To the best of our knowledge, this is the first report on novel mcr-3 variant (mcr-3.19). ConclusionsThe significant role of mcr-like genes in different Aeromonas species remains unknown and needs additional investigation to understand the insights on colistin resistance mechanism.

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Genetic and Functional Characterization of an MCR-3-Like Enzyme-Producing Escherichia coli Isolate Recovered from Swine in Brazil

Cited by 42 publications

References 38 publications

mcr-9 , an Inducible Gene Encoding an Acquired Phosphoethanolamine Transferase in Escherichia coli, and Its Origin

mcr-9 , an Inducible Gene Encoding an Acquired Phosphoethanolamine Transferase in Escherichia coli, and Its Origin

Antimicrobial Resistance in Farm Animals in Brazil: An Update Overview

First hybrid complete genome ofAeromonas veroniireveals chromosome-mediated novel structural variantmcr-3.19from human clinical specimen

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