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An allelic variant of the PmrB sensor kinase responsible for colistin resistance in an Escherichia coli strain of clinical origin.
Sci Rep. 2017 07 11; 7(1):5071.SR

Abstract

We investigated the colistin resistance mechanism in an Escherichia coli strain (LC711/14) isolated in Italy in 2014, from an urinary tract infection, which was previously shown to express a colistin resistance mechanism different from mcr-1. LC711/14 was found to carry a novel mutation in the pmrB gene, resulting in a leucine to proline amino acid substitution at position 10 of the PmrB sensor kinase component of the PmrAB signal transduction system. The role of this substitution in colistin resistance was documented by expression of the wild-type and mutated alleles in a pmrB deletion derivative of the E. coli reference strain MG1655, in which expression of the mutated allele conferred colistin resistance and upregulation of the endogenous pmrHFIJKLM lipid A modification system. Complementation of LC711/14 with the wild-type pmrB allele restored colistin susceptibility and decreased expression of pmrHFIJKLM, confirming the role of this PmrB mutation. Substitution of leucine at position 10 of PmrB with other amino acids (glycine and glutamine) resulted in loss of function, underscoring a key role of this residue which is located in the cytoplasmic secretion domain of the protein. This work demonstrated that mutation in this domain of the PmrB sensor kinase can be responsible for acquired colistin resistance in E. coli strains of clinical origin.

Authors+Show Affiliations

University of Siena, Department of Medical Biotechnologies, Siena, 53100, Italy.University of Siena, Department of Medical Biotechnologies, Siena, 53100, Italy.University of Siena, Department of Medical Biotechnologies, Siena, 53100, Italy.University of Florence, Department of Surgery and Translational Medicine, Florence, 50134, Italy.Lecco A. Manzoni Hospital, Clinical Microbiology and Virology Unit, Lecco, 23900, Italy.Lecco A. Manzoni Hospital, Clinical Microbiology and Virology Unit, Lecco, 23900, Italy.University of Florence, Department of Experimental and Clinical Medicine, Florence, 50134, Italy.University of Siena, Department of Medical Biotechnologies, Siena, 53100, Italy. gianmaria.rossolini@unifi.it. University of Florence, Department of Experimental and Clinical Medicine, Florence, 50134, Italy. gianmaria.rossolini@unifi.it. Florence Careggi University Hospital, Clinical Microbiology and Virology Unit, Florence, 50134, Italy. gianmaria.rossolini@unifi.it.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28698568

Citation

Cannatelli, Antonio, et al. "An Allelic Variant of the PmrB Sensor Kinase Responsible for Colistin Resistance in an Escherichia Coli Strain of Clinical Origin." Scientific Reports, vol. 7, no. 1, 2017, p. 5071.
Cannatelli A, Giani T, Aiezza N, et al. An allelic variant of the PmrB sensor kinase responsible for colistin resistance in an Escherichia coli strain of clinical origin. Sci Rep. 2017;7(1):5071.
Cannatelli, A., Giani, T., Aiezza, N., Di Pilato, V., Principe, L., Luzzaro, F., Galeotti, C. L., & Rossolini, G. M. (2017). An allelic variant of the PmrB sensor kinase responsible for colistin resistance in an Escherichia coli strain of clinical origin. Scientific Reports, 7(1), 5071. https://doi.org/10.1038/s41598-017-05167-6
Cannatelli A, et al. An Allelic Variant of the PmrB Sensor Kinase Responsible for Colistin Resistance in an Escherichia Coli Strain of Clinical Origin. Sci Rep. 2017 07 11;7(1):5071. PubMed PMID: 28698568.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An allelic variant of the PmrB sensor kinase responsible for colistin resistance in an Escherichia coli strain of clinical origin. AU - Cannatelli,Antonio, AU - Giani,Tommaso, AU - Aiezza,Noemi, AU - Di Pilato,Vincenzo, AU - Principe,Luigi, AU - Luzzaro,Francesco, AU - Galeotti,Cesira L, AU - Rossolini,Gian Maria, Y1 - 2017/07/11/ PY - 2016/10/11/received PY - 2017/05/25/accepted PY - 2017/7/13/entrez PY - 2017/7/13/pubmed PY - 2019/1/29/medline SP - 5071 EP - 5071 JF - Scientific reports JO - Sci Rep VL - 7 IS - 1 N2 - We investigated the colistin resistance mechanism in an Escherichia coli strain (LC711/14) isolated in Italy in 2014, from an urinary tract infection, which was previously shown to express a colistin resistance mechanism different from mcr-1. LC711/14 was found to carry a novel mutation in the pmrB gene, resulting in a leucine to proline amino acid substitution at position 10 of the PmrB sensor kinase component of the PmrAB signal transduction system. The role of this substitution in colistin resistance was documented by expression of the wild-type and mutated alleles in a pmrB deletion derivative of the E. coli reference strain MG1655, in which expression of the mutated allele conferred colistin resistance and upregulation of the endogenous pmrHFIJKLM lipid A modification system. Complementation of LC711/14 with the wild-type pmrB allele restored colistin susceptibility and decreased expression of pmrHFIJKLM, confirming the role of this PmrB mutation. Substitution of leucine at position 10 of PmrB with other amino acids (glycine and glutamine) resulted in loss of function, underscoring a key role of this residue which is located in the cytoplasmic secretion domain of the protein. This work demonstrated that mutation in this domain of the PmrB sensor kinase can be responsible for acquired colistin resistance in E. coli strains of clinical origin. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/28698568/An_allelic_variant_of_the_PmrB_sensor_kinase_responsible_for_colistin_resistance_in_an_Escherichia_coli_strain_of_clinical_origin_ L2 - http://dx.doi.org/10.1038/s41598-017-05167-6 DB - PRIME DP - Unbound Medicine ER -