A predominant ColE-plasmid prototype is associated with dissemination of the mcr-4 resistance gene in German E. coli isolates from food and livestock

Background and objectives: Colistin is considered as highest priority critically important antibiotic, only used to treat human infections caused by multidrug-resistant Gram-negative bacteria. So far, seven different mobile colistin resistance-genes are known. Here, characteristics of mcr-4-positive colistin-resistant E. coli isolates from the national monitoring for antimicrobial resistance in zoonotic agents from the food chain were summarized.

Materials and methods: Antimicrobial resistance was determined by broth microdilution according to CLSI guidelines and EUCAST epidemiological cut-off values. Resistant E. coli were subjected to mcr-PCR, S1-PFGE, MiSeq-sequencing (WGS) and bioinformatics. Transferability of mcr-4 carrying plasmids was investigated by filter mating experiments.

Results: Up to now, 13 mcr-4-positive out of 756  colistin-resistant E. coli isolates, recovered between 2010 and 2017, were identified. Sanger sequencing revealed that two variants, mcr-4.2 and mcr-4.3, are prevalent among these isolates. WGS showed that the isolates differ in their MLST-, sero- and fim-type. However, all of them carry a highly conserved ColE-plasmid prototype that partially differs in size and genetic composition.

Conclusion: Our findings indicate that mcr-4 occurs sporadically among colistin-resistant E. coli from food and livestock. However, further information on the biology and genetics are needed to assess the impact of this resistance determinant on public health.