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

Area of Science:

• Microbiology
• Immunology
• Genetics

Background:

• MCR-1 is a plasmid-encoded enzyme conferring colistin resistance in Enterobacteriaceae.
• Its presence in human, animal, and environmental strains raises global health concerns.
• MCR-1 modifies lipid A structure, impacting bacterial interactions with host defenses.

Purpose of the Study:

• To investigate the impact of MCR-1 expression on E. coli-induced inflammatory pathways in a human macrophage model.
• To determine if MCR-1 affects host innate immune responses beyond colistin resistance.

Main Methods:

• Utilized recombinant mcr-1-expressing Escherichia coli strains.
• Employed activated THP-1 cells as a model for human macrophages.
• Analyzed p38-MAPK, JNK activation, pNF-κB translocation, and pro-inflammatory cytokine gene expression (TNF-α, IL-12, IL-1β).
• Assessed Caspase-1 activity and IL-1β secretion.

Main Results:

• MCR-1 expression significantly modulated p38-MAPK and JNK activation and pNF-κB nuclear translocation.
• Expression of pro-inflammatory cytokines TNF-α, IL-12, and IL-1β was altered by MCR-1.
• Caspase-1 activity and IL-1β secretion were reduced in mcr-1-positive E. coli infections.
• Results were corroborated using clinical isolates of mcr-1-positive E. coli.

Conclusions:

• MCR-1 expression in E. coli suppresses key host innate immune signaling pathways.
• This immune evasion contributes to reduced early host defense activation.
• MCR-1 may promote bacterial survival by subverting innate immunity, in addition to conferring colistin resistance.