Microcins mediate competition among Enterobacteriaceae in the inflamed gut Original paper

What was studied?

This study examined the role of microcins produced by Escherichia coli Nissle 1917 (EcN) in mediating competition among Enterobacteriaceae in the inflamed gut. The researchers investigated how these small antimicrobial peptides enabled EcN to limit the expansion of both commensal and pathogenic Enterobacteriaceae, particularly under iron-limiting conditions, which are common during intestinal inflammation. The team conducted in vitro and in vivo experiments using mouse models of colitis to observe the impact of EcN’s microcin production on the gut microbiota, focusing on its ability to outcompete pathogens, such as Salmonella enterica, and pathobionts, including adherent-invasive E. coli (AIEC).

Who was studied?

The study primarily focused on Escherichia coli Nissle 1917 (EcN), its microcin-producing wild-type strain, and mutant strains incapable of producing microcins. The in vivo experiments were performed using specific pathogen-free (SPF) C57BL/6 mice treated with dextran sulfate sodium (DSS) to induce colitis, and germ-free mice to study colonization in the absence of pre-existing microbiota. Additionally, Salmonella enterica serovar Typhimurium (STm), AIEC, and a commensal E. coli (cEc) strain were used to model pathogen competition within the gut. Colonization levels, microbial community composition, and histopathological changes in the intestines were assessed.

Most important findings

The study demonstrated that microcins produced by EcN enabled it to limit the growth of competing Enterobacteriaceae during colitis. EcN’s microcin genes (mcmA and mchB) were expressed under iron-limited conditions, enabling EcN to outcompete Salmonella and commensal E. coli in the inflamed gut. In DSS-treated mice, wild-type EcN reduced Salmonella colonization, while microcin mutants showed significantly lower competitive ability. Microcins, however, did not considerably impact the gut microbiota, suggesting their narrow-spectrum activity. Furthermore, therapeutic administration of wild-type EcN reduced Salmonella colonization and associated inflammation, with microcin mutants showing reduced effectiveness. This study provides the first in vivo evidence of microcin-mediated competition within the gut, showing microcins as a potential therapeutic tool for enterobacterial infections in inflammatory conditions.

Key implications

The findings suggest that microcins could be developed as targeted therapeutic agents to treat enterobacterial infections, particularly in the context of gut inflammation. Since microcins help beneficial bacteria, such as EcN, outcompete pathogens, they may offer an alternative to broad-spectrum antibiotics, preserving beneficial gut microbiota while suppressing harmful pathogens. Additionally, their role in nutrient competition, particularly for iron, highlights a potential pathway for manipulating gut microbial dynamics during dysbiosis or disease. The therapeutic use of microcin-producing probiotics may be beneficial for conditions such as colitis and inflammatory bowel diseases.