title: Fructose-asparagine is a primary nutrient during growth of Salmonella in the inflamed intestine.
abstract: Salmonella enterica serovar Typhimurium (Salmonella) is one of the most significant food-borne pathogens affecting both humans and agriculture. We have determined that Salmonella encodes an uptake and utilization pathway specific for a novel nutrient, fructose-asparagine (F-Asn), which is essential for Salmonella fitness in the inflamed intestine (modeled using germ-free, streptomycin-treated, ex-germ-free with human microbiota, and IL10-/- mice). The locus encoding F-Asn utilization, fra, provides an advantage only if Salmonella can initiate inflammation and use tetrathionate as a terminal electron acceptor for anaerobic respiration (the fra phenotype is lost in Salmonella SPI1- SPI2- or ttrA mutants, respectively). The severe fitness defect of a Salmonella fra mutant suggests that F-Asn is the primary nutrient utilized by Salmonella in the inflamed intestine and that this system provides a valuable target for novel therapies.
authors: Department of Microbiology, The Ohio State University, Columbus, Ohio, United States of America; Department of Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors: Mohamed M
authors: MM
authors: Ali
authors: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors: David L
authors: DL
authors: Newsom
authors: Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, United States of America.
authors: Juan F
authors: JF
authors: González
authors: Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, United States of America.
authors: Anice
authors: A
authors: Sabag-Daigle
authors: Department of Microbiology, The Ohio State University, Columbus, Ohio, United States of America.
authors: Christopher
authors: C
authors: Stahl
authors: Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, United States of America.
authors: Brandi
authors: B
authors: Steidley
authors: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, United States of America.
authors: Judith
authors: J
authors: Dubena
authors: Department of Microbiology, The Ohio State University, Columbus, Ohio, United States of America.
authors: Jessica L
authors: JL
authors: Dyszel
authors: Department of Microbiology, The Ohio State University, Columbus, Ohio, United States of America.
authors: Jenee N
authors: JN
authors: Smith
authors: Department of Microbiology, The Ohio State University, Columbus, Ohio, United States of America.
authors: Yakhya
authors: Y
authors: Dieye
authors: Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America.
authors: Razvan
authors: R
authors: Arsenescu
authors: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, United States of America.
authors: Prosper N
authors: PN
authors: Boyaka
authors: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, United States of America.
authors: Steven
authors: S
authors: Krakowka
authors: Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, United States of America.
authors: Tony
authors: T
authors: Romeo
authors: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, United States of America.
authors: Edward J
authors: EJ
authors: Behrman
authors: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors: Peter
authors: P
authors: White
authors: Department of Microbiology, The Ohio State University, Columbus, Ohio, United States of America; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, United States of America.
authors: Brian M M
authors: BM
authors: Ahmer
mesh_terms: D000693:Anaerobiosis; D000818:Animals; D001216:Asparagine / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics; D001692:Biological Transport / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics; D005632:Fructose / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D016753:Interleukin-10 / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012480:Salmonella Infections / Q000378:metabolism*; D012481:Salmonella Infections, Animal / Q000235:genetics; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D001216:Asparagine; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D005632:Fructose; D016753:Interleukin-10; D008565:Membrane Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; C556062:IL10 protein, mouse; C440638:SPI-2 protein, Salmonella; C419942:Spi1 protein, Salmonella