{"id":"doi:10.1128/mbio.00853-19","kind":"article","title":"Identification of Novel Mobilized Colistin Resistance Gene mcr-9 in a Multidrug-Resistant, Colistin-Susceptible Salmonella enterica Serotype Typhimurium Isolate","authors":["Carroll LM","Gaballa A","Guldimann C","Sullivan G","Henderson LO","Wiedmann M"],"author_count":6,"year":2019,"published":"2019-05-07","venue":"mBio","cited_by":417,"doi":"10.1128/mbio.00853-19","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1128/mbio.00853-19","archive_url":"https://space-kitty.com/papers/doi:10.1128/mbio.00853-19","updated":null,"pmid":"31064835","pmcid":"PMC6509194","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6509194/pdf","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.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Identification of Novel Mobilized Colistin Resistance Gene mcr-9 in a Multidrug-Resistant, Colistin-Susceptible Salmonella enterica Serotype Typhimurium Isolate\" by Carroll LM, Gaballa A, Guldimann C et al., https://doi.org/10.1128/mbio.00853-19, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"infectious-disease-amr","name":"Infectious Disease, Vaccines & Antimicrobial Resistance","domain_slug":"medicine"}],"cited_in_dossiers":[]}