title: ASalmonellaRegulator Modulates Intestinal Colonization and Use of Phosphonoacetic Acid.
abstract: Many microorganisms produce phosphonates, molecules characterized by stable carbon-phosphorus bonds that store phosphorus or act as antimicrobials. The role of phosphonates in the marine biosphere is well characterized but the role of these molecules in the intestine is poorly understood.Salmonella entericauses its virulence factors to influence the host immune response to compete with the host and normal microflora for nutrients.Salmonellacannot produce phosphonates but encodes the enzymes to use them suggesting that it is exposed to phosphonates during its life cycle. The role of phosphonates during enteric salmonellosis is unexplored. We have previously shown thatSTM3602, encoding a putative regulator of phosphonate metabolism, is needed for colonization in calves. Here, we report that the necessity ofSTM3602in colonization of the murine intestine results from multiple factors.STM3602is needed for full activation of the type-3 secretion system-1 and for optimal invasion of epithelial cells. The ΔSTM3602mutant grows poorly in phosphonoacetic acid (PA) as the sole phosphorus source, but can use 2-aminoethylphosphonate. PhnA, an enzyme required for PA breakdown, is not controlled by STM3602 suggesting an additional mechanism for utilization of PA inS. Typhimurium. Finally, the requirement ofSTM3602for intestinal colonization differs depending on the composition of the microflora. Our data suggest thatSTM3602has multiple regulatory targets that are necessary for survival within the microbial community in the intestine. Determination of the members of theSTM3602regulon may illuminate new pathways needed for colonization of the host.
authors.affiliation: Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University Health Science CenterBryan, TX, USA; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State UniversityRaleigh, NC, USA.
authors.forename: Johanna R
authors.initials: JR
authors.lastname: Elfenbein
authors.affiliation: Paul G. Allen School for Global Animal Health, College of Veterinary Medicine, Washington State University Pullman, WA, USA.
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Knodler
authors.affiliation: Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University Health Science Center Bryan, TX, USA.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Schaeffer
authors.affiliation: Department of Medial Microbiology and Immunology, School of Medicine, University of California Davis Davis, CA, USA.
authors.forename: Franziska
authors.initials: F
authors.lastname: Faber
authors.affiliation: Department of Medial Microbiology and Immunology, School of Medicine, University of California Davis Davis, CA, USA.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
authors.affiliation: Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University Health Science Center Bryan, TX, USA.
authors.forename: Helene L
authors.initials: HL
authors.lastname: Andrews-Polymenis
mesh_terms: D000818:Animals; D015964:Gene Expression Regulation, Bacterial; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010746:Phosphonoacetic Acid / Q000378:metabolism*; D012481:Salmonella Infections, Animal / Q000382:microbiology*; D019779:Salmonella enterica / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D010746:Phosphonoacetic Acid
keywords: Salmonella; infection; mice; phosphonates; phosphonoacetic acid