Heterogeneity and Diversity of mcr-8 Genetic Context in Chicken-Associated Klebsiella pneumoniae

ABSTRACT

Increasing mobile colistin resistance, mediated by the mcr gene family, in Enterobacteriaceae has become a global concern. Among the 10 reported mcr genes, mcr-8 was first identified in Klebsiella pneumoniae, which could cause severe infections with high mortality. Information about the prevalence and genetic context of mcr-8 is still lacking. In this study, we found that mcr-8 was present in 9.83% of K. pneumoniae isolates of chicken origin. S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting showed that the mcr-8 gene was located on a plasmid in all of the isolates. The genetic context of the plasmids exhibited considerable diversity from the whole-genome sequence through Illumina and MinION long-read sequencing. Mutations in two-component systems may function synergistically with mcr-8, resulting in extremely high resistance to colistin. In addition to colistin resistance, these plasmids also contained genes conferring resistance to beta-lactams, tetracycline, aminoglycosides, sulfonamides, macrolides, chloramphenicol, and florfenicol. Therefore, these findings indicate that the genetic context of mcr-8 is heterogeneous and diverse and that mcr-8 and certain chromosomal mechanisms jointly contribute to high-level colistin resistance in K. pneumoniae strains, which provides new insights into the resistance mechanisms of K. pneumoniae.