Emergence of mcr-9.1 in ESBL-producing Clinical Enterobacteriaceae in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome and Mobilome

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Abstract Background Extended-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 little therapeutic options. Methods Eleven clinical Enterobacteriaceae strains with resistance to cephems and/or colistin were genomically analysed to determine their resistome, mobilome, and evolutionary relationship to global strains. The global phylogenomics of mcr-9.1- bearing genomes were further analysed. Results & conclusion 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 bla CTX-M-15 bla TEM-1 and mcr-9.1 were found in single isolates; IS Ec9 , IS 19 , and Tn 3 transposons bracketed bla CTX-M-15 and bla TEM-1 . Common plasmid types included IncF, IncH and ColRNAI. Genomes bearing mcr-9.1 clustered into six main phyletic groups (A-F), with those of this study belonging to clade B. Enterobacter sp . and Salmonella sp . are the main hosts of mcr-9.1 globally, albeit 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.

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