Sialic acids comprise a varied group of nine-carbon amino sugars widely distributed among mammals and higher metazoans. Commensal and pathogenic bacteria that colonise heavily sialiated niches (e.g. the mammalian respiratory tract and gut) can scavenge sialic acids from their surrounding environment. Scavenged sialic acid is used as a carbon, nitrogen and energy source, or to evade the host immune response by decorating their outer surfaces in sialic acid.
Bacterial sialic acid specific membrane protein transport systems have been identified that belong to the tripartite ATP-independent periplasmic transporters, ATP-binding cassette, major facilitator superfamily and sodium solute symporter transport transport systems.
Here we report the unpublished 1.95 Å resolution crystal structure of a sialic acid specific sodium solute symporter, SiaT, in its outward-open conformation. The structure of SiaT was determined in complex with sodium and sialic acid bound, providing insight into how this transporter mediates the movement of sialic acid across the membrane. The overall structure contains 13 transmembrane helices where the structural core is formed from two inverted repeats of five transmembrane helices each, as seen in other sodium symporters, including the galactose transporter (vSGLT), and leucine transporter (LeuT).
A sodium molecule occupies the cation-binding site equivalent to the Na2-site in LeuT-like (FIRL) fold transporters. A putative sodium site was also found at a previously proposed sodium escape pathway on the intracellular side. Structural and biochemical analyses elucidate essential transport residues and for the first time, a sialic acid transporter has been characterised. Molecular modeling and molecular dynamics simulations provide insight on the transport mechanism employed by SiaT. Overall, this work provides new data that enriches our understanding of sialic acid import in bacterial pathogens, which is a novel and unexplored target for antibiotic drug design.