Microcins mediate competition among Enterobacteriaceae in the inflamed gut

Certain commensal enterobacteria secrete small proteins called microcins that suppress the growth of other bacteria in the inflamed gut, conferring an intra- and interspecies competitive advantage. Microcins are small secreted proteins composed of relatively few peptides, secreted by certain commensal enterobacteria . They are known to be antimicrobial in vitro, but their role in vivo is unclear. This study shows that microcin expression enables the probiotic bacteria, Escherichia coli, to limit expansion of competing Enterobacteriaceae during intestinal inflammation. Therapeutic administration of microcin-producing bacteria substantially reduced intestinal colonization of pathogenic bacteria in mice. This is the first evidence that microcins mediate inter- and intra-species competition and may be useful as narrow-spectrum therapeutics to inhibit enteric pathogens and reduce enterobacterial blooms. The Enterobacteriaceae are a family of Gram-negative bacteria that include commensal organisms as well as primary and opportunistic pathogens that are among the leading causes of morbidity and mortality worldwide. Although Enterobacteriaceae often comprise less than 1% of a healthy intestine’s microbiota1, some of these organisms can bloom in the inflamed gut2,3,4,5; expansion of enterobacteria is a hallmark of microbial imbalance known as dysbiosis6. Microcins are small secreted proteins that possess antimicrobial activity in vitro7,8, but whose role in vivo has been unclear. Here we demonstrate that microcins enable the probiotic bacterium Escherichia coli Nissle 1917 (EcN) to limit the expansion of competing Enterobacteriaceae (including pathogens and pathobionts) during intestinal inflammation. Microcin-producing EcN limits the growth of competitors in the inflamed intestine, including commensal E. coli, adherent–invasive E. coli and the related pathogen Salmonella enterica. Moreover, only therapeutic administration of the wild-type, microcin-producing EcN to mice previously infected with S. enterica substantially reduced intestinal colonization by the pathogen. Our work provides the first evidence that microcins mediate inter- and intraspecies competition among the Enterobacteriaceae in the inflamed gut. Moreover, we show that microcins can act as narrow-spectrum therapeutics to inhibit enteric pathogens and reduce enterobacterial blooms.