title: Characterization of the ecological role of genes mediating acid resistance in Lactobacillus reuteri during colonization of the gastrointestinal tract.
abstract: Rodent-derived strains of Lactobacillus reuteri densely colonize the forestomach of mice and possess several genes whose predicted functions constitute adaptations towards an acidic environment. The objective of this study was to systematically determine which genes of L. reuteri 100-23 contribute to tolerance towards host gastric acid secretion. Genes predicted to be involved in acid resistance were inactivated, and their contribution to survival under acidic conditions was confirmed in model gastric juice. Fitness of five mutants that showed impaired in vitro acid resistance were then compared through competition experiments in ex-germ-free mice that were either treated with omeprazole, a proton-pump inhibitor that suppresses acid secretion in the stomach, or left untreated. This analysis revealed that the urease cluster was the predominant factor in mediating resistance to gastric acid production. Population levels of the mutant, which were substantially decreased in untreated mice, were almost completely restored through omeprazole, demonstrating that urease production in L. reuteri is mainly devoted to overcome gastric acid. The findings provide novel information on the mechanisms by which L. reuteri colonizes its gastric niche and demonstrate that in silico gene predictions and in vitro tests have limitations for predicting the ecological functions of colonization factors in bacterial symbionts.
authors.affiliation: Department of Food Science and Technology, University of Nebraska, Lincoln, NE, USA.|School of Biological Sciences, University of Nebraska, Lincoln, NE, USA.
authors.forename: Janina A
authors.initials: JA
authors.lastname: Krumbeck
authors.affiliation: Department of Food Science and Technology, University of Nebraska, Lincoln, NE, USA.
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Marsteller
authors.affiliation: Department of Food Science and Technology, University of Nebraska, Lincoln, NE, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Frese
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Peterson
authors.affiliation: Department of Food Science and Technology, University of Nebraska, Lincoln, NE, USA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Ramer-Tait
authors.affiliation: Department of Food Science and Technology, University of Nebraska, Lincoln, NE, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Hutkins
authors.affiliation: Department of Food Science and Technology, University of Nebraska, Lincoln, NE, USA.|Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.|Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada.
authors.forename: Jens
authors.initials: J
authors.lastname: Walter
mesh_terms: D000143:Acids / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000382:microbiology*; D052200:Limosilactobacillus reuteri / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D014510:Urease / Q000235:genetics / Q000378:metabolism
chemical_list: D000143:Acids; D001426:Bacterial Proteins; D014510:Urease