title: Zinc deficiency alters host response and pathogen virulence in a mouse model of enteroaggregative Escherichia coli-induced diarrhea.
abstract: Enteroaggregative Escherichia coli (EAEC) is increasingly recognized as a major cause of diarrheal disease globally. In the current study, we investigated the impact of zinc deficiency on the host and pathogenesis of EAEC. Several outcomes of EAEC infection were investigated including weight loss, EAEC shedding and tissue burden, leukocyte recruitment, intestinal cytokine expression, and virulence expression of the pathogen in vivo. Mice fed a protein source defined zinc deficient diet (dZD) had an 80% reduction of serum zinc and a 50% reduction of zinc in luminal contents of the bowel compared to mice fed a protein source defined control diet (dC). When challenged with EAEC, dZD mice had significantly greater weight loss, stool shedding, mucus production, and, most notably, diarrhea compared to dC mice. Zinc deficient mice had reduced infiltration of leukocytes into the ileum in response to infection suggesting an impaired immune response. Interestingly, expression of several EAEC virulence factors were increased in luminal contents of dZD mice. These data show a dual effect of dietary zinc in benefitting the host while impairing virulence of the pathogen. The study demonstrates the critical importance of zinc and may help elucidate the benefits of zinc supplementation in cases of childhood diarrhea and malnutrition.
authors.affiliation: a Center for Global Health ; Division of Infectious Diseases and International Health ; School of Medicine ; University of Virginia ; Charlottesville , VA USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Bolick
authors.forename: Glynis L
authors.initials: GL
authors.lastname: Kolling
authors.forename: John H
authors.initials: JH
authors.lastname: Moore
authors.forename: Luís Antônio
authors.initials: LA
authors.lastname: de Oliveira
authors.forename: Kenneth
authors.initials: K
authors.lastname: Tung
authors.forename: Casandra
authors.initials: C
authors.lastname: Philipson
authors.forename: Monica
authors.initials: M
authors.lastname: Viladomiu
authors.forename: Raquel
authors.initials: R
authors.lastname: Hontecillas
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
mesh_terms: D000818:Animals; D057138:Bacterial Shedding; D001835:Body Weight; D003967:Diarrhea / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004926:Escherichia coli / Q000302:isolation & purification*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D007082:Ileum / Q000473:pathology; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D015032:Zinc / Q000172:deficiency*
chemical_list: D015032:Zinc
keywords: Cftr, cystic fibrosis transmembrane regulator; EAEC, Enteroaggregative Escherichia coli; Enteroaggregative Escherichia coli; dC, defined control diet; dZD, defined zinc deficient diet; diarrhea; enteropathy; virulence; zinc deficiency