Dissemination dynamics of colistin resistance genes mcr-9 and mcr-10 across diverse Inc plasmid backbones
Odion O. Ikhimiukor, Manuela Montoya-Giraldo, Stephanie S. R. Souza, Ifeoluwa Akintayo, Nicole I. Zac Soligno, Maitiú Marmion, Elissa M. Eckhardt, Nisalda Carreiro, Adrienne A. Workman, Isabella W. Martin, Cheryl P. Andam
Abstract
The polymyxin antibiotic colistin is used as a final line of treatment for life threatening infections caused by multidrug resistant and carbapenem-resistant Gram-negative bacteria. Mobile colistin resistance genes mcr-9 and mcr-10 are increasingly detected in Enterobacteriaceae but their epidemiology is poorly understood. The genetic characteristics of mcr-9 and mcr-10, being the only mobile colistin resistance genes detected in a local population of Enterobacter species isolated from bloodstream infections in Dartmouth Hitchcock Medical Center, USA, were elucidated and contextualized against a global dataset of mcr-9/10-bearing plasmids using genomic and phylogenetic tools. Seven out of 59 Enterobacter isolates carry either an mcr-9 or mcr-10 on a plasmid with distinct single and multiple replicon configurations, including IncFIB(pECLA), IncFIB(K), IncFIA(HI1)—IncFIB(K), IncFIB(pECLA)--IncFII(pECLA) and IncFIB(K)--IncFII(pECLA), whereas two genomes harbor mcr-9 on their chromosome. Global contextualization reveals that allelic variants of mcr-9 and mcr-10 are widely disseminated across diverse Inc-type plasmids, transcending geographic and taxonomic boundaries. Plasmid-borne genes conferring resistance to other antimicrobial agents, such as aminoglycoside, tetracycline and trimethoprim, tend to co-occur with mcr-9.1 and mcr-9.2 alleles. Findings from this study enhance our understanding of the plasmid backgrounds of mcr-9 and mcr-10, their associated antimicrobial resistance gene carriage and co-occurrence. This knowledge may be critical to inform scalable and effective public health interventions aimed at preserving the efficacy of colistin. Multi-drug resistant bacteria are bacteria that cause infections and are not killed by many commonly used antibiotics. Colistin is an antibiotic used to treat serious infections caused by multi-drug resistant bacteria. Several parts of the DNA that encode genes, such as mcr-9 and mcr-10, are linked to colistin resistance in bacteria. We studied bloodstream infection bacteria from a hospital in the United States to see how often they carry these genes and whether they have similar characteristics to other bacteria. We found characteristics of the bacteria that may also enable them to survive treatment with other antibiotics. Understanding why bacteria are resistant to antibiotics is helpful to guide public health efforts against multidrug resistant bacteria and optimize the use of antibiotics such as colistin. Ikhimiukor et al. investigate the plasmid backgrounds of colistin resistance genes mcr-9 and mcr-10 at both hospital-level and global level. Plasmid-borne mcr-9.1 and mcr-9.2 alleles are carried by a variety of Inc plasmids and often co-occur with other resistance genes, suggesting possible co-selection and raising concerns about treatment options.