title: Giardia duodenalis-induced alterations of commensal bacteria kill Caenorhabditis elegans: a new model to study microbial-microbial interactions in the gut.
abstract: Giardia duodenalis is the most common cause of parasitic diarrhea worldwide and a well-established risk factor for postinfectious irritable bowel syndrome. We hypothesized that Giardia-induced disruptions in host-microbiota interactions may play a role in the pathogenesis of giardiasis and in postgiardiasis disease. Functional changes induced by Giardia in commensal bacteria and the resulting effects on Caenorhabditis elegans were determined. Although Giardia or bacteria alone did not affect worm viability, combining commensal Escherichia coli bacteria with Giardia became lethal to C. elegans. Giardia also induced killing of C. elegans with attenuated Citrobacter rodentium espF and map mutant strains, human microbiota from a healthy donor, and microbiota from inflamed colonic sites of ulcerative colitis patient. In contrast, combinations of Giardia with microbiota from noninflamed sites of the same patient allowed for worm survival. The synergistic lethal effects of Giardia and E. coli required the presence of live bacteria and were associated with the facilitation of bacterial colonization in the C. elegans intestine. Exposure to C. elegans and/or Giardia altered the expression of 172 genes in E. coli. The genes affected by Giardia included hydrogen sulfide biosynthesis (HSB) genes, and deletion of a positive regulator of HSB genes, cysB, was sufficient to kill C. elegans even in the absence of Giardia. Our findings indicate that Giardia induces functional changes in commensal bacteria, possibly making them opportunistic pathogens, and alters host-microbe homeostatic interactions. This report describes the use of a novel in vivo model to assess the toxicity of human microbiota.
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada; Host-Parasite Interactions, NSERC-CREATE Program, University of Calgary, Calgary, Alberta, Canada;
authors.forename: Teklu K
authors.initials: TK
authors.lastname: Gerbaba
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada;
authors.forename: Pratyush
authors.initials: P
authors.lastname: Gupta
authors.affiliation: Department of Medicine, University of Calgary, Calgary, Alberta, Canada; and.
authors.forename: Kevin
authors.initials: K
authors.lastname: Rioux
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada;
authors.forename: Dave
authors.initials: D
authors.lastname: Hansen
authors.affiliation: Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada; Host-Parasite Interactions, NSERC-CREATE Program, University of Calgary, Calgary, Alberta, Canada; Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada aburet@ucalgary.ca.
authors.forename: Andre G
authors.initials: AG
authors.lastname: Buret
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000382:microbiology*; D016022:Case-Control Studies; D044082:Citrobacter rodentium / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D003093:Colitis, Ulcerative / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D016829:Giardia lamblia / Q000378:metabolism / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D050296:Microbial Viability; D064307:Microbiota; D013559:Symbiosis; D013997:Time Factors; D014774:Virulence
chemical_list: D029968:Escherichia coli Proteins
keywords: Giardia; functional changes; homeostasis hydrogen sulfide biosynthesis; microbiota