Co-transfer of mcr-8 with blaNDM-1 or tmexCD1-toprJ1 by plasmid hybridisation

Carbapenems, tigecycline and colistin are three important antimicrobial agents for the treatment of clinical infections caused by multidrug-resistant Enterobacteriaceae. Here we characterised the formation of hybrid plasmids containing mcr-8 and bla NDM-1 or tmexCD1-toprJ1 that could confer resistance to colistin and carbapenems or tigecycline. More specifically, these clinically important genes could be co-transferred through IS 26 - and ltrA -mediated plasmid fusion to clinical isolates during conjugation under single drug (colistin) selection, following which the recipient strains became carbapenem- or tigecycline-resistant. The transferability and stability of these hybrid multidrug resistance (MDR) plasmids depend on the bacterial host and the presence of antibiotics. Further evolution and adaptation of these hybrid plasmids may facilitate their emergence and spread, which is of great concern for clinical therapy.