mcr-1 Gene Expression Modulates the Inflammatory Response of Human Macrophages to Escherichia coli.

MCR-1 is a plasmid-encoded phosphoethanolamine transferase able to modify the lipid A structure. It confers resistance to colistin and was isolated from human, animal, and environmental strains of Enterobacteriaceae , raising serious global health concerns. In this paper, we used recombinant mcr-1 -expressing Escherichia coli to study the impact of MCR-1 products on E. coli -induced activation of inflammatory pathways in activated THP-1 cells, which was used as a model of human macrophages. We found that infection with recombinant mcr-1 -expressing E. coli significantly modulated p38-MAPK and Jun N-terminal protein kinase (JNK) activation and pNF-κB nuclear translocation as well as the expression of genes for the relevant proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and IL-1β compared with mcr-1 -negative strains. Caspase-1 activity and IL-1β secretion were significantly less activated by mcr-1 -positive E. coli strains than the mcr-1 -negative parental strain. Similar results were obtained with clinical isolates of mcr-1 -positive E. coli , suggesting that, in addition to colistin resistance, the expression of mcr-1 allows the escape of early host innate defenses and may promote bacterial survival.
(Copyright © 2020 American Society for Microbiology.)