The Salmonella enterica serovar Typhimurium virulence factor STM3169 is a hexuronic acid binding protein component of a TRAP transporter.

Reyme Herman,Gavin H Thomas,Amna Afzal,Abbas Maqbool,Andrew Leech,Cavan Bennett-Ness

doi:10.1099/mic.0.000967

Abstract

The intracellular pathogen S. Typhimurium is a leading cause of foodborne illness across the world and is known to rely on a range of virulence factors to colonize the human host and cause disease. The gene coding for one such factor, stm3169, was determined to be upregulated upon macrophage entry and its disruption reduces survival in the macrophage. In this study we characterize the STM3169 protein, which forms the substrate binding protein (SBP) of an uncharacterized tripartite ATP-independent periplasmic (TRAP) transporter. Genome context analysis of the genes encoding this system in related bacteria suggests a function in sugar acid transport. We demonstrate that purified STM3169 binds d-glucuronic acid with high affinity and specificity. S. Typhimurium LT2 can use this sugar acid as a sole carbon source and the genes for a probable catabolic pathway are present in the genome. As this gene was previously implicated in macrophage survival, it suggests a role for d-glucuronate as an important carbon source for S. Typhimurium in this environment.

Highlights

Non-typhoidal Salmonella is a leading cause of foodborne illness worldwide [1]
STM3169 is the substrate binding protein (SBP) component that initially binds the substrate in the periplasm; this component is usually expressed at high levels relative to the membrane domains, consistent with the high abundance of the STM3169 protein in the Haneda et al study [7, 14]
tripartite ATPindependent periplasmic (TRAP) transporters form a large family of diverse SBPdependent secondary transporters in bacteria, the functions of which are, largely, to move organic acids into bacterial cells [15,16,17]

Summary

Introduction

Non-typhoidal Salmonella is a leading cause of foodborne illness worldwide [1]. In particular, Salmonella enterica serovar Typhimurium Typhimurium LT2, the stm3169–stm3171 TRAP transporter gene cluster is not found in a region containing any other associated genes that give any clue to its substrate and cellular function (Fig. S1a, available in the online version of this article). Genome analysis of stm3169 orthologues from related gamma-proteobacteria revealed a range of different cluster architectures that strongly suggest a role in sugar acid import and catabolism for these strains (Fig. 1).

Results

Conclusion