Identification of Novel Mobilized Colistin Resistance Gene <italic toggle="yes">mcr-9</italic> in a Multidrug-Resistant, Colistin-Susceptible <named-content content-type="genus-species">Salmonella enterica</named-content> Serotype Typhimurium Isolate

ABSTRACT Mobilized colistin resistance (mcr) genes are plasmid-borne genes that confer resistance to colistin, an antibiotic used to treat severe bacterial infections. To date, eight known mcr homologues have been described (mcr-1 to -8). Here, we describe mcr-9, a novel mcr homologue detected durin...

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Autores principales:	Laura M. Carroll, Ahmed Gaballa, Claudia Guldimann, Genevieve Sullivan, Lory O. Henderson, Martin Wiedmann
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Salmonella enterica antibiotic resistance colistin mcr genes mcr-9 mobilized colistin resistance Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5f93cf4e5f9c476c864aafeaad662cc9
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spelling	oai:doaj.org-article:5f93cf4e5f9c476c864aafeaad662cc92021-11-15T15:55:25ZIdentification of Novel Mobilized Colistin Resistance Gene <italic toggle="yes">mcr-9</italic> in a Multidrug-Resistant, Colistin-Susceptible <named-content content-type="genus-species">Salmonella enterica</named-content> Serotype Typhimurium Isolate10.1128/mBio.00853-192150-7511https://doaj.org/article/5f93cf4e5f9c476c864aafeaad662cc92019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00853-19https://doaj.org/toc/2150-7511ABSTRACT Mobilized colistin resistance (mcr) genes are plasmid-borne genes that confer resistance to colistin, an antibiotic used to treat severe bacterial infections. To date, eight known mcr homologues have been described (mcr-1 to -8). Here, we describe mcr-9, a novel mcr homologue detected during routine in silico screening of sequenced Salmonella genomes for antimicrobial resistance genes. The amino acid sequence of mcr-9, detected in a multidrug-resistant (MDR) Salmonella enterica serotype Typhimurium (S. Typhimurium) strain isolated from a human patient in Washington State in 2010, most closely resembled mcr-3, aligning with 64.5% amino acid identity and 99.5% coverage using Translated Nucleotide BLAST (tblastn). The S. Typhimurium strain was tested for phenotypic resistance to colistin and was found to be sensitive at the 2-mg/liter European Committee on Antimicrobial Susceptibility Testing breakpoint under the tested conditions. mcr-9 was cloned in colistin-susceptible Escherichia coli NEB5α under an IPTG (isopropyl-β-d-thiogalactopyranoside)-induced promoter to determine whether it was capable of conferring resistance to colistin when expressed in a heterologous host. Expression of mcr-9 conferred resistance to colistin in E. coli NEB5α at 1, 2, and 2.5 mg/liter colistin, albeit at a lower level than mcr-3. Pairwise comparisons of the predicted protein structures associated with all nine mcr homologues (Mcr-1 to -9) revealed that Mcr-9, Mcr-3, Mcr-4, and Mcr-7 share a high degree of similarity at the structural level. Our results indicate that mcr-9 is capable of conferring phenotypic resistance to colistin in Enterobacteriaceae and should be immediately considered when monitoring plasmid-mediated colistin resistance. IMPORTANCE Colistin is a last-resort antibiotic that is used to treat severe infections caused by MDR and extensively drug-resistant (XDR) bacteria. The World Health Organization (WHO) has designated colistin as a “highest priority critically important antimicrobial for human medicine” (WHO, Critically Important Antimicrobials for Human Medicine, 5th revision, 2017, https://www.who.int/foodsafety/publications/antimicrobials-fifth/en/), as it is often one of the only therapies available for treating serious bacterial infections in critically ill patients. Plasmid-borne mcr genes that confer resistance to colistin pose a threat to public health at an international scale, as they can be transmitted via horizontal gene transfer and have the potential to spread globally. Therefore, the establishment of a complete reference of mcr genes that can be used to screen for plasmid-mediated colistin resistance is essential for developing effective control strategies.Laura M. CarrollAhmed GaballaClaudia GuldimannGenevieve SullivanLory O. HendersonMartin WiedmannAmerican Society for MicrobiologyarticleSalmonella entericaantibiotic resistancecolistinmcr genesmcr-9mobilized colistin resistanceMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Salmonella enterica antibiotic resistance colistin mcr genes mcr-9 mobilized colistin resistance Microbiology QR1-502
spellingShingle	Salmonella enterica antibiotic resistance colistin mcr genes mcr-9 mobilized colistin resistance Microbiology QR1-502 Laura M. Carroll Ahmed Gaballa Claudia Guldimann Genevieve Sullivan Lory O. Henderson Martin Wiedmann Identification of Novel Mobilized Colistin Resistance Gene <italic toggle="yes">mcr-9</italic> in a Multidrug-Resistant, Colistin-Susceptible <named-content content-type="genus-species">Salmonella enterica</named-content> Serotype Typhimurium Isolate
description	ABSTRACT Mobilized colistin resistance (mcr) genes are plasmid-borne genes that confer resistance to colistin, an antibiotic used to treat severe bacterial infections. To date, eight known mcr homologues have been described (mcr-1 to -8). Here, we describe mcr-9, a novel mcr homologue detected during routine in silico screening of sequenced Salmonella genomes for antimicrobial resistance genes. The amino acid sequence of mcr-9, detected in a multidrug-resistant (MDR) Salmonella enterica serotype Typhimurium (S. Typhimurium) strain isolated from a human patient in Washington State in 2010, most closely resembled mcr-3, aligning with 64.5% amino acid identity and 99.5% coverage using Translated Nucleotide BLAST (tblastn). The S. Typhimurium strain was tested for phenotypic resistance to colistin and was found to be sensitive at the 2-mg/liter European Committee on Antimicrobial Susceptibility Testing breakpoint under the tested conditions. mcr-9 was cloned in colistin-susceptible Escherichia coli NEB5α under an IPTG (isopropyl-β-d-thiogalactopyranoside)-induced promoter to determine whether it was capable of conferring resistance to colistin when expressed in a heterologous host. Expression of mcr-9 conferred resistance to colistin in E. coli NEB5α at 1, 2, and 2.5 mg/liter colistin, albeit at a lower level than mcr-3. Pairwise comparisons of the predicted protein structures associated with all nine mcr homologues (Mcr-1 to -9) revealed that Mcr-9, Mcr-3, Mcr-4, and Mcr-7 share a high degree of similarity at the structural level. Our results indicate that mcr-9 is capable of conferring phenotypic resistance to colistin in Enterobacteriaceae and should be immediately considered when monitoring plasmid-mediated colistin resistance. IMPORTANCE Colistin is a last-resort antibiotic that is used to treat severe infections caused by MDR and extensively drug-resistant (XDR) bacteria. The World Health Organization (WHO) has designated colistin as a “highest priority critically important antimicrobial for human medicine” (WHO, Critically Important Antimicrobials for Human Medicine, 5th revision, 2017, https://www.who.int/foodsafety/publications/antimicrobials-fifth/en/), as it is often one of the only therapies available for treating serious bacterial infections in critically ill patients. Plasmid-borne mcr genes that confer resistance to colistin pose a threat to public health at an international scale, as they can be transmitted via horizontal gene transfer and have the potential to spread globally. Therefore, the establishment of a complete reference of mcr genes that can be used to screen for plasmid-mediated colistin resistance is essential for developing effective control strategies.
format	article
author	Laura M. Carroll Ahmed Gaballa Claudia Guldimann Genevieve Sullivan Lory O. Henderson Martin Wiedmann
author_facet	Laura M. Carroll Ahmed Gaballa Claudia Guldimann Genevieve Sullivan Lory O. Henderson Martin Wiedmann
author_sort	Laura M. Carroll
title	Identification of Novel Mobilized Colistin Resistance Gene <italic toggle="yes">mcr-9</italic> in a Multidrug-Resistant, Colistin-Susceptible <named-content content-type="genus-species">Salmonella enterica</named-content> Serotype Typhimurium Isolate
title_short	Identification of Novel Mobilized Colistin Resistance Gene <italic toggle="yes">mcr-9</italic> in a Multidrug-Resistant, Colistin-Susceptible <named-content content-type="genus-species">Salmonella enterica</named-content> Serotype Typhimurium Isolate
title_full	Identification of Novel Mobilized Colistin Resistance Gene <italic toggle="yes">mcr-9</italic> in a Multidrug-Resistant, Colistin-Susceptible <named-content content-type="genus-species">Salmonella enterica</named-content> Serotype Typhimurium Isolate
title_fullStr	Identification of Novel Mobilized Colistin Resistance Gene <italic toggle="yes">mcr-9</italic> in a Multidrug-Resistant, Colistin-Susceptible <named-content content-type="genus-species">Salmonella enterica</named-content> Serotype Typhimurium Isolate
title_full_unstemmed	Identification of Novel Mobilized Colistin Resistance Gene <italic toggle="yes">mcr-9</italic> in a Multidrug-Resistant, Colistin-Susceptible <named-content content-type="genus-species">Salmonella enterica</named-content> Serotype Typhimurium Isolate
title_sort	identification of novel mobilized colistin resistance gene <italic toggle="yes">mcr-9</italic> in a multidrug-resistant, colistin-susceptible <named-content content-type="genus-species">salmonella enterica</named-content> serotype typhimurium isolate
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/5f93cf4e5f9c476c864aafeaad662cc9
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Identification of Novel Mobilized Colistin Resistance Gene <italic toggle="yes">mcr-9</italic> in a Multidrug-Resistant, Colistin-Susceptible <named-content content-type="genus-species">Salmonella enterica</named-content> Serotype Typhimurium Isolate

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