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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-06-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00853-19 |
| _version_ | 1818740336513515520 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T01:39:07Z |
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| publishDate | 2019-06-01 |
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| spelling | doaj.art-5f93cf4e5f9c476c864aafeaad662cc92022-12-21T21:25:24ZengAmerican Society for MicrobiologymBio2150-75112019-06-0110310.1128/mBio.00853-19Identification 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 IsolateLaura M. Carroll0Ahmed Gaballa1Claudia Guldimann2Genevieve Sullivan3Lory O. Henderson4Martin Wiedmann5Department of Food Science, Cornell University, Ithaca, New York, USADepartment of Food Science, Cornell University, Ithaca, New York, USAInstitute for Food Safety and Hygiene, University of Zurich, Zurich, SwitzerlandDepartment of Food Science, Cornell University, Ithaca, New York, USADepartment of Food Science, Cornell University, Ithaca, New York, USADepartment of Food Science, Cornell University, Ithaca, New York, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.00853-19Salmonella entericaantibiotic resistancecolistinmcr genesmcr-9mobilized colistin resistance |
| spellingShingle | 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 mBio Salmonella enterica antibiotic resistance colistin mcr genes mcr-9 mobilized colistin resistance |
| 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_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_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_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 |
| topic | Salmonella enterica antibiotic resistance colistin mcr genes mcr-9 mobilized colistin resistance |
| url | https://journals.asm.org/doi/10.1128/mBio.00853-19 |
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