Microcins can act as therapeutics to treat enterobacterial colitis.

February 14, 2017

A recent study published in Nature has demonstrated that microcins mediate competition among Enterobacteriaceae in the inflamed gut.

Antibiotics with a broad-spectrum have been shown to be unsuccessful in treating enterobacterial gut infections. Research efforts point to identify new therapeutic treatments, studying the mechanisms used by beneficial microbes to mediate colonization resistance to pathogens. Reports dating back to 1978 regarding microcin-producing Enterobacteriaceae in human stool samples suggested that microcins contribute to gut microbial ecology.

Antimicrobial weapons are produced throughout the whole living kingdom and probably the oldest antimicrobial strategy in living organisms is the use of antimicrobial peptides. Bacteria secrete defense peptides called bacteriocins that they use for microbial competitions. Microcins are very small bacteriocins produced by Escherichia coli and related enterobacteria. They are ribosomally synthesized peptides that can be further post-translationally modified. Microcins possess potent antimicrobial activity in vitro, but, before this study, the role in vivo for microcins has been unclear.

Sassone-Corsi and coworkers identify an in vivo role for microcins studying the probiotic bacterium Escherichia coli Nissle 1917 (EcN) and its interplay with related competitors in the gut.

They demonstrate that the probiotic bacterium EcN utilizes microcins to limit the expansion of competing Enterobacteriaceae (including pathogens and pathobionts) during intestinal inflammation. The authors show that microcins enable EcN to limit the growth of a commensal E. coli, an adherent-invasive E. coli and the related enteric pathogen Salmonella enterica serovar Typhimurium (STm).

Interestingly, the authors also demonstrate that microcins could therapeutically treat an active enterobacterial infection by administration of wild-type EcN to mice infected previously with diarrheal Salmonella enterica. Indeed, mice receiving wild-type EcN after infection with Salmonella show substantially reduced level of gut colonization by Salmonella, reduced inflammation and weight loss.

In conclusion, this work shows also that microcins, therapeutically capable of reducing the colonization of an enteric pathogen in the inflamed gut, could act as narrow-spectrum therapeutics to inhibit enteric pathogens and treat enterobacterial colitis.

Journal reference:

M. Sassone-Corsi et al., Microcins mediate competition among Enterobacteriaceae in the inflamed gut. Nature 540, 280–283 (2016).