title: Microcins mediate competition among Enterobacteriaceae in the inflamed gut.
abstract: 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 microbiota, some of these organisms can bloom in the inflamed gut; expansion of enterobacteria is a hallmark of microbial imbalance known as dysbiosis. Microcins are small secreted proteins that possess antimicrobial activity in vitro, 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.
authors: Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, California 92697, USA.|Institute for Immunology, University of California Irvine, Irvine, California 92697, USA.
authors: Martina
authors: M
authors: Sassone-Corsi
authors: Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, California 92697, USA.|Institute for Immunology, University of California Irvine, Irvine, California 92697, USA.
authors: Sean-Paul
authors: SP
authors: Nuccio
authors: Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, California 92697, USA.
authors: Henry
authors: H
authors: Liu
authors: Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, California 92697, USA.
authors: Dulcemaria
authors: D
authors: Hernandez
authors: Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, California 92697, USA.
authors: Christine T
authors: CT
authors: Vu
authors: Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, California 92697, USA.
authors: Amy A
authors: AA
authors: Takahashi
authors: Institute for Immunology, University of California Irvine, Irvine, California 92697, USA.|Department of Pathology and Laboratory Medicine, University of California, Irvine, California 92697, USA.
authors: Robert A
authors: RA
authors: Edwards
authors: Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, California 92697, USA.|Institute for Immunology, University of California Irvine, Irvine, California 92697, USA.
authors: Manuela
authors: M
authors: Raffatellu
mesh_terms: D000818:Animals; D001430:Bacteriocins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D064806:Dysbiosis / Q000382:microbiology; D004755:Enterobacteriaceae / Q000254:growth & development* / Q000472:pathogenicity; D004926:Escherichia coli / Q000145:classification / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019936:Probiotics / Q000378:metabolism; D019779:Salmonella enterica / Q000254:growth & development / Q000472:pathogenicity; D013559:Symbiosis
chemical_list: D001430:Bacteriocins; C020411:microcin