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The plasmid-mediated Kluyvera-like arnBCADTEF operon confers colistin (hetero) resistance to Escherichia coli

Antimicrobial Agents and Chemotherapy publish this investigation article

April 19th, 2021

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 and by still unknown mechanisms. This work analyzed 74 E. 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% were carried by highly mobile plasmids, followed by four strains lacking previously known resistance determinants or two with mcr-4 (one 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 down-regulation that was also observed in the four isolates lacking known resistance determinants, three of them sharing the same macrorestriction and plasmid profiles. Genomic sequencing of one of these strains, isolated from a bovine in 2015, revealed a IncFII plasmid of 62.1 Kb encoding 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




Gallardo A., Iglesias M., Ugarte-Ruiz M., Hernandez M., Miguela-Villoldo P., Gutierrez G., Rodriguez-Lazaro D., Dominguez L. and Quesada A.




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The plasmid-mediated Kluyvera-like arnBCADTEF operon confers colistin (hetero) resistance to Escherichia coli

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The plasmid-mediated Kluyvera-like arnBCADTEF operon confers colistin (hetero) resistance to Escherichia coli



Participants:

Universidad de ExtremaduraDepartamento de Bioquímica, Biología Molecular y Genética. Facultad de Veterinaria. Universidad de Extremadura (UNEX).

Universidad ComplutenseServicio de Zoonosis de Transmisión Alimentaria y Resistencia a Antimicrobianos (ZTA). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).

Instituto Tecnológico Agrario de Castilla y LeónLaboratorio de Biología Molecular y Microbiología. Instituto Tecnológico Agrario de Castilla y León (ITACyL).

Universidad de BurgosUnidad de Microbiología. Departamento de Biotecnología y Ciencia de los Alimentos. Universidad de Burgos (UBU).

Universidad de ExtremaduraInstituto Universitario de Biotecnología Ganadera y Cinegética (INBIO G+C). Universidad de Extremadura (UNEX).







Antimicrobial Agents and Chemotherapy
FACTOR YEAR Q
4.904 2019

NLMID: 315061

PMID: 33685891

ISSN: 0066-4804



TITLE: The plasmid-mediated Kluyvera-like arnBCADTEF operon confers colistin (hetero) resistance to Escherichia coli


JOURNAL: Antimicrob. Agents Chemother.


NUMERACIÓN: 65(5):e00091-21


AÑO: 2021


PUBLISHER: American Society for Microbiology


AUTHORS: Gallardo A., Iglesias M., Ugarte-Ruiz M., Hernandez M., Miguela-Villoldo P., Gutierrez G., Rodriguez-Lazaro D., Dominguez L. and Quesada A.


VISAVET PARTICIPANTS


3rd
María Ugarte Ruiz
5th
Pedro Miguela Villoldo
8th
Lucas Domínguez Rodríguez

DOI: https://doi.org/ 10.1128/AAC.00091-21


CITE THIS PUBLICATION:

Gallardo A., Iglesias M., Ugarte-Ruiz M., Hernandez M., Miguela-Villoldo P., Gutierrez G., Rodriguez-Lazaro D., Dominguez L. and Quesada A. The plasmid-mediated Kluyvera-like arnBCADTEF operon confers colistin (hetero) resistance to Escherichia coli. Antimicrobial Agents and Chemotherapy. 65(5):e00091-21. 2021. (A). ISSN: 0066-4804. DOI: 10.1128/AAC.00091-21


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