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

Sarah C Hennebry,Timothy Scott,Leanne C Sait,Andreas Kupz,Thomas J Humphrey,Ji Yang,Raju Mantena,Samantha J Richardson,Richard A Strugnell

doi:10.1371/journal.pone.0046675

Sarah C Hennebry, Timothy Scott + Show 7 more

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https://doi.org/10.1371/journal.pone.0046675

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Abstract

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.

Highlights

IntroductionTyphimurium) (and other serovars of Salmonella enterica subspecies I) survive in the alimentary tract of adult poultry, often without causing significant systemic disease [1]
BLAST results revealed the presence of transthyretin-like protein (TLP) genes in all Salmonella species and serovars sequenced
The phylogeny of periplasmic TLP genes We have previously shown that several bacteria possess more than one copy of the TLP gene, typically one encoding a cytosolic TLP and another encoding a periplasmic TLP [4]

Summary

Introduction

Typhimurium) (and other serovars of Salmonella enterica subspecies I) survive in the alimentary tract of adult poultry, often without causing significant systemic disease [1]. The subsequent contamination of chicken carcasses during processing is thought to be a major cause of food poisoning. Understanding the mechanisms which allow Salmonella to survive in such an environment is an important aspect of developing strategies which could reduce human food-borne salmonellosis. Much of the research concerning Salmonella pathogenesis is extrapolated from studies in the mouse model of enteric fever. The genes required for pathogenesis in a murine system (or any mammalian system), are not necessarily those which are required for colonisation of the alimentary tract of poultry. Throughout its evolution, Salmonella has been associated with reptilian and avian hosts.

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