Emergence of mcr-9.1 in extended-spectrum-β-lactamase-producing clinical Enterobacteriaceae in Pretoria, South Africa : global evolutionary phylogenomics, resistome, and mobilome

dc.contributor.authorOsei Sekyere, John
dc.contributor.authorManingi, Nontuthuko Excellent
dc.contributor.authorModipane, Lesedi
dc.contributor.authorMbelle, Nontombi Marylucy
dc.date.accessioned2020-12-23T09:13:21Z
dc.date.available2020-12-23T09:13:21Z
dc.date.issued2020-05
dc.descriptionSupplemental material: FIG S1. A dendrogram showing the phylogenetic relationship between mcr gene variants from different Gram-negative bacteria (chromosomes and plasmids). The bootstrap values are shown in red and represent the bootstrap values in Fig. 1B. TABLE S1. Antimicrobial sensitivity results and resistome of the isolates. The sensitivity of the isolates to the various antibiotics tested using MicroScan is shown, with those colored green being resistant according to the CLSI breakpoints. Those colored blue are resistant according to the EUCAST breakpoints. Those not colored are susceptible. The various antibiotic classes to which the antibiotic agents belong are shown above each antibiotic in unique colors, and the resistance genes per isolate are shown in the last column. DATA SET S1. General data of demographic, phenotypic, and genomic results used for this study. DATA SET S2. Sequences and alignment of contigs harboring the mcr-9.1 genes DATA SET S3. Sequences of mcr gene variants.en_ZA
dc.description.abstractExtended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae are critical-priority pathogens that cause substantial fatalities. With the emergence of mobile mcr genes mediating resistance to colistin in Enterobacteriaceae, clinicians are now left with few therapeutic options. Eleven clinical Enterobacteriaceae strains with resistance to cephems and/or colistin were genomically analyzed to determine their resistomes, mobilomes, and evolutionary relationships to global strains. The global phylogenomics of mcr genes and mcr-9.1-bearing genomes were further analyzed. Ten isolates were ESBL positive. The isolates were multidrug resistant and phylogenetically related to global clones but distant from local strains. Multiple resistance genes, including blaCTX-M-15 blaTEM-1, and mcr-9.1, were found in single isolates; ISEc9, IS19, and Tn3 transposons bracketed blaCTX-M-15 and blaTEM-1. Common plasmid types included IncF, IncH, and ColRNAI. mcr-9 was of close sequence identity to mcr-3, mcr-5, mcr-7, mcr-8, and mcr-10. Genomes bearing mcr-9.1 clustered into six main phyletic groups (A to F), with those of this study belonging to clade B. Enterobacter species and Salmonella species are the main hosts of mcr-9.1 globally, although diverse promiscuous plasmids disseminate mcr-9.1 across different bacterial species. Emergence of mcr-9.1 in ESBL-producing Enterobacteriaceae in South Africa is worrying, due to the restricted therapeutic options. Intensive One Health molecular surveillance might discover other mcr alleles and inform infection management and antibiotic choices. IMPORTANCE: Colistin is currently the last-resort antibiotic for difficult-to-treat bacterial infections. However, colistin resistance genes that can move from bacteria to bacteria have emerged, threatening the safe treatment of many bacterial infections. One of these genes, mcr-9.1, has emerged in South Africa in bacteria that are multidrug resistant, further limiting treatment options for clinicians. In this work, we show that this new gene is disseminating worldwide through Enterobacter and Salmonella species through multiple plasmids. This worrying observation requires urgent action to prevent further escalation of this gene in South Africa and Africa.en_ZA
dc.description.departmentMedical Microbiologyen_ZA
dc.description.librarianpm2020en_ZA
dc.description.urihttp://msystems.asm.orgen_ZA
dc.identifier.citationSekyere, J.O., Maningi, N.E., Modipane, L. et al. 2020, 'Emergence of mcr-9.1 in extended-spectrum-β-lactamase-producing clinical Enterobacteriaceae in Pretoria, South Africa : global evolutionary phylogenomics, resistome, and mobilome', mSystems, vol. 5, no. 3, art. e00148-20, pp. 1-23.en_ZA
dc.identifier.issn2379-5077 (online)
dc.identifier.other10.1128/mSystems.00148-20
dc.identifier.urihttp://hdl.handle.net/2263/77496
dc.language.isoenen_ZA
dc.publisherAmerican Society for Microbiologyen_ZA
dc.rights© 2020 Osei Sekyere et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.en_ZA
dc.subjectEnterobacteriaceaeen_ZA
dc.subjectCritical pathogensen_ZA
dc.subjectColistin resistanceen_ZA
dc.subjectExtended-spectrum-β-lactamase (ESBL)en_ZA
dc.subjectSouth Africa (SA)en_ZA
dc.subjectMobilomeen_ZA
dc.subjectPhylogenomicsen_ZA
dc.subjectResistomeen_ZA
dc.subjectMcr-9.1en_ZA
dc.titleEmergence of mcr-9.1 in extended-spectrum-β-lactamase-producing clinical Enterobacteriaceae in Pretoria, South Africa : global evolutionary phylogenomics, resistome, and mobilomeen_ZA
dc.typeArticleen_ZA

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