Tripartite ATP-Independent Periplasmic (TRAP) Transporters and Tripartite Tricarboxylate Transporters (TTT): From Uptake to Pathogenicity.

Leonardo T Rosa,Gavin H Thomas,David J Kelly,Matheus E Bianconi

doi:10.3389/fcimb.2018.00033

Abstract

The ability to efficiently scavenge nutrients in the host is essential for the viability of any pathogen. All catabolic pathways must begin with the transport of substrate from the environment through the cytoplasmic membrane, a role executed by membrane transporters. Although several classes of cytoplasmic membrane transporters are described, high-affinity uptake of substrates occurs through Solute Binding-Protein (SBP) dependent systems. Three families of SBP dependant transporters are known; the primary ATP-binding cassette (ABC) transporters, and the secondary Tripartite ATP-independent periplasmic (TRAP) transporters and Tripartite Tricarboxylate Transporters (TTT). Far less well understood than the ABC family, the TRAP transporters are found to be abundant among bacteria from marine environments, and the TTT transporters are the most abundant family of proteins in many species of β-proteobacteria. In this review, recent knowledge about these families is covered, with emphasis on their physiological and structural mechanisms, relating to several examples of relevant uptake systems in pathogenicity and colonization, using the SiaPQM sialic acid uptake system from Haemophilus influenzae and the TctCBA citrate uptake system of Salmonella typhimurium as the prototypes for the TRAP and TTT transporters, respectively. High-throughput analysis of SBPs has recently expanded considerably the range of putative substrates known for TRAP transporters, while the repertoire for the TTT family has yet to be fully explored but both types of systems most commonly transport carboxylates. Specialized spectroscopic techniques and site-directed mutagenesis have enriched our knowledge of the way TRAP binding proteins capture their substrate, while structural comparisons show conserved regions for substrate coordination in both families. Genomic and protein sequence analyses show TTT SBP genes are strikingly overrepresented in some bacteria, especially in the β-proteobacteria and some α-proteobacteria. The reasons for this are not clear but might be related to a role for these proteins in signaling rather than transport.

Highlights

The ability to efficiently scavenge nutrients in the host is essential for the viability of any pathogen
As with the Tripartite ATP-independent periplasmic (TRAP) transporters, systems in the Tricarboxylate Transporters (TTT) family are composed of a conserved 12 TM protein, (TctA homologs) believed to act as a symport protein energized by an electrochemical ion-gradient and poorly-conserved 4 TM protein (TctB homologs) with unknown function, in combination with an Solute Binding-Protein (SBP) (TctC homologs) which binds the substrate with high affinity (Figure 1, Sweet et al, 1979; Winnen et al, 2003)
We showed how transport systems from the TRAP and TTT families can play important roles in bacteria with a focus on pathogenicity and colonization

Summary

Introduction

The ability to efficiently scavenge nutrients in the host is essential for the viability of any pathogen. A subsequent study showed that a SiaP homolog was involved in the uptake of sialic acid in this bacterium (Steenbergen et al, FIGURE 1 | Overall topologies and structures of the different Solute Binding Protein (SBP dependant) transporter families.

Results

Conclusion