PMID- 25483331 OWN - NLM STAT- MEDLINE DCOM- 20150903 LR - 20220330 IS - 1949-0984 (Electronic) IS - 1949-0976 (Print) IS - 1949-0976 (Linking) VI - 5 IP - 5 DP - 2014 TI - Zinc deficiency alters host response and pathogen virulence in a mouse model of enteroaggregative Escherichia coli-induced diarrhea. PG - 618-27 LID - 10.4161/19490976.2014.969642 [doi] AB - 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. FAU - Bolick, David T AU - Bolick DT AD - a Center for Global Health ; Division of Infectious Diseases and International Health ; School of Medicine ; University of Virginia ; Charlottesville , VA USA. FAU - Kolling, Glynis L AU - Kolling GL FAU - Moore, John H 2nd AU - Moore JH 2nd FAU - de Oliveira, Luis Antonio AU - de Oliveira LA FAU - Tung, Kenneth AU - Tung K FAU - Philipson, Casandra AU - Philipson C FAU - Viladomiu, Monica AU - Viladomiu M FAU - Hontecillas, Raquel AU - Hontecillas R FAU - Bassaganya-Riera, Josep AU - Bassaganya-Riera J FAU - Guerrant, Richard L AU - Guerrant RL LA - eng GR - D43 TW006578/TW/FIC NIH HHS/United States GR - D43TW006578/TW/FIC NIH HHS/United States GR - HHSN272201000056C/PHS HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Gut Microbes JT - Gut microbes JID - 101495343 RN - J41CSQ7QDS (Zinc) SB - IM MH - Animals MH - Bacterial Shedding MH - Body Weight MH - Diarrhea/*immunology/*microbiology/pathology MH - Disease Models, Animal MH - Disease Susceptibility MH - Escherichia coli/*isolation & purification MH - Escherichia coli Infections/*immunology/*microbiology/pathology MH - Ileum/pathology MH - Leukocytes/immunology MH - Male MH - Mice MH - Zinc/*deficiency PMC - PMC4615194 OTO - NOTNLM OT - Cftr, cystic fibrosis transmembrane regulator OT - EAEC, Enteroaggregative Escherichia coli OT - Enteroaggregative Escherichia coli OT - dC, defined control diet OT - dZD, defined zinc deficient diet OT - diarrhea OT - enteropathy OT - virulence OT - zinc deficiency EDAT- 2014/12/09 06:00 MHDA- 2015/09/04 06:00 PMCR- 2015/10/30 CRDT- 2014/12/09 06:00 PHST- 2014/12/09 06:00 [entrez] PHST- 2014/12/09 06:00 [pubmed] PHST- 2015/09/04 06:00 [medline] PHST- 2015/10/30 00:00 [pmc-release] AID - 969642 [pii] AID - 10.4161/19490976.2014.969642 [doi] PST - ppublish SO - Gut Microbes. 2014;5(5):618-27. doi: 10.4161/19490976.2014.969642.