Characterisation of the function and mechanism of a binding-protein dependent secondary transporter

点击翻译按钮获取中文摘要

Many bacteria rely almost completely on being able to acquire nutrients from their environment and in bacteria that can only live inside our bodies these chemicals often come from us. One bacterium, Haemophilus influenzae, uses a chemical called sialic acid as a nutrient but also covers its surface in this molecule allowing it to become invisible to components of our immune system. This bacterium is able to acquire the sialic acid using a particular collection of proteins in its membrane called a TRAP transporter. This project aims to study in detail the TRAP transporter that is essential for sialic acid uptake by H. influenzae. If we can determine exactly how this transporter works, we have a better chance at being able to develop novel antimicrobials against this bacterium as we have already demonstrated that if this system is inactive then H. influenzae cannot causes disease. In addition, this TRAP transporter is very amenable to study in the laboratory and we wish to use this particular system to learn a lot of general things about how these transporters work. They are not just limited to functioning in sialic acid uptake, but different TRAP transporters have evolved to transport a wide range of compounds and are present in a wide range of environment, for example, many bacteria that live in the sea (in salty environments) appears to have many TRAP transporters. One of the objectives of this project to try and find out if the presence of salt (sodium) is important for the mechanism of TRAP transporters, which would correlate with them being used preferentially by marine organisms. The results of the project will tell us much more about how one human pathogen is able to capture sialic acid, but also the basic mechanims used by thousands of other bacteria to capture chemicals from the environment using TRAP transporters.