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 lipid A structure. It confers resistance to colistin and was isolated in 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, used as a model of human macrophages.We found that infection with recombinant mcr-1 expressing E. coli significantly modulated p38-MAPK, JNK activation and pNF-kB nuclear translocation as well as the expression of genes for the relevant pro-inflammatory cytokines TNF-α, IL-12 and IL-1β compared to mcr1-negative strains. Caspase-1 activity and IL-1β secretion were significantly less activated by mcr-1- positive E. coli strains compared to 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.