title: A glycine betaine importer limits Salmonella stress resistance and tissue colonization by reducing trehalose production.
abstract: Mechanisms by which Salmonella establish chronic infections are not well understood. Microbes respond to stress by importing or producing compatible solutes, small molecules that stabilize proteins and lipids. The Salmonella locus opuABCD (also called OpuC) encodes a predicted importer of the compatible solute glycine betaine. Under stress conditions, if glycine betaine cannot be imported, Salmonella enterica produce the disaccharide trehalose, a highly effective compatible solute. We demonstrate that strains lacking opuABCD accumulate more trehalose under stress conditions than wild-type strains. ΔopuABCD mutant strains are more resistant to high-salt, low-pH and -hydrogen peroxide, conditions that mimic aspects of innate immunity, in a trehalose-dependent manner. In addition, ΔopuABCD mutant strains require the trehalose production genes to out-compete wild-type strains in mice and macrophages. These data suggest that in the absence of opuABCD, trehalose accumulation increases bacterial resistance to stress in broth and mice. Thus, opuABCD reduces bacterial colonization via a mechanism that limits trehalose production. Mechanisms by which microbes limit disease may reveal novel pathways as therapeutic targets.
authors.affiliation: Department of Molecular Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA. piloniet@colorado.edu
authors.forename: M Carolina
authors.initials: MC
authors.lastname: Pilonieta
authors.forename: Toni A
authors.initials: TA
authors.lastname: Nagy
authors.forename: Dana R
authors.initials: DR
authors.lastname: Jorgensen
authors.forename: Corrella S
authors.initials: CS
authors.lastname: Detweiler
mesh_terms: D000818:Animals; D001622:Betaine / Q000378:metabolism*; D004195:Disease Models, Animal; D017353:Gene Deletion; D006861:Hydrogen Peroxide / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000382:microbiology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D054712:Salinity; D012481:Salmonella Infections, Animal; D012486:Salmonella typhimurium / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity*; D012492:Salts / Q000633:toxicity; D013312:Stress, Physiological; D014199:Trehalose / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D012492:Salts; D001622:Betaine; D014199:Trehalose; D006861:Hydrogen Peroxide