Salmonella Typhimurium's Transthyretin-Like Protein Is a Host-Specific Factor Important in Fecal Survival in Chickens

• Published in: PloS one Vol. 7; no. 12; p. e46675
• Main Authors: Hennebry, Sarah C., Sait, Leanne C., Mantena, Raju, Humphrey, Thomas J., Yang, Ji, Scott, Timothy, Kupz, Andreas, Richardson, Samantha J., Strugnell, Richard A.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.12.2012; Public Library of Science (PLoS)
• Subjects: Acids; Amino acid sequence; Amino acids; Animal models; Animals; Aromatic compounds; Bacteria; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Base Sequence; Biochemistry; Biology; Chickens; Chickens - microbiology; Computational Biology; Contamination; Copper; Disseminated infection; E coli; Enzymatic activity; Enzyme activity; Enzymes; Escherichia coli; Evolution; Feces; Feces - microbiology; Fishes; Food contamination & poisoning; Gastrointestinal Tract - microbiology; Gene Expression Regulation, Bacterial; Genes; Homology; Host Specificity - genetics; Immunology; In vivo methods and tests; Inoculation; Laboratories; Male; Mammals; Medicine; Metabolism; Mice; Molecular biology; Molecular Sequence Data; Mutation; Oxidation; Pathogenesis; Periplasm - genetics; Phylogeny; Poultry; Prealbumin - chemistry; Prealbumin - genetics; Prealbumin - metabolism; Protein binding; Protein Transport; Proteins; Purines - metabolism; Retinoids; Salmonella; Salmonella Infections - microbiology; Salmonella Infections - transmission; Salmonella Typhimurium; Salmonella typhimurium - cytology; Salmonella typhimurium - genetics; Salmonella typhimurium - metabolism; Salmonella typhimurium - physiology; Survival; Thyroid gland; Thyroid hormones; Thyroxine; Tlp gene; Transthyretin; Uric acid; Virulence; Virulence (Microbiology); Virulence factors; Vitamin A; Australia; Victoria Australia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0046675

The transthyretin-like protein (TLP) from Salmonella enterica subspecies I is a periplasmic protein with high level structural similarity to a protein found in mammals and fish. In humans, the protein homologue, transthyretin, binds and carries retinol and thyroxine, and a series of other, unrelated aromatic compounds. Here we show that the amino acid sequence of the TLP from different species, subspecies and serovars of the Salmonella genus is highly conserved and demonstrate that the TLP gene is constitutively expressed in S. Typhimurium and that copper and other divalent metal ions severely inhibit enzyme activity of the TLP, a cyclic amidohydrolase that hydrolyses 5-hydroxyisourate (5-HIU). In order to determine the in vivo role of the S. Typhimurium TLP, we constructed a strain of mouse-virulent S. Typhimurium SL1344 bearing a mutation in the TLP gene (SL1344 ΔyedX). We assessed the virulence of this strain via oral inoculation of mice and chickens. Whilst SL1344 ΔyedX induced a systemic infection in both organisms, the bacterial load detected in the faeces of infected chickens was significantly reduced when compared to the load of S. Typhimurium SL1344. These data demonstrate that the TLP gene is required for survival of S. Typhimurium in a high uric acid environment such as chicken faeces, and that metabolic traits of Salmonellae in natural and contrived hosts may be fundamentally different. Our data also highlight the importance of using appropriate animal models for the study of bacterial pathogenesis especially where host-specific virulence factors or traits are the subject of the study.