BBSRC MIBTP - How does iron availability regulate protein translocation in bacteria?

The goal of this project is to understand the mechanistic basis for the response of bacteria to nutritional immunity.
One strategy that is used by animals to control bacterial growth is limiting availability of essential metal ions, such as iron—a process known as nutritional immunity. For example, despite being iron rich, the iron available to bacteria in the blood is extremely low, which limits bacterial growth. In contrast to blood, the gut hosts a diverse microbiome and is normally relatively iron replete. However, during inflammation, hosts discourage bacterial growth by restricting the availability of iron. In order to persist in the gut during inflammation, bacterial commensals such as Escherichia coli have to respond to rapid changes in iron availability. In addition, rapid changes in iron availability are frequently a signal for invasion for bacterial pathogens. Understanding how bacteria respond to changes in metal-ion availability will help us (1) to understand how the normal (good) gut microbiota responds during infection by a pathogenic species, (2) to understand how bacterial pathogens invade during infection and (3) to develop more effective antibacterial strategies for both the biotech and food industries.
Recent work in the Huber lab suggests that the transport of proteins across the cytoplasmic membrane in bacteria is regulated by iron availability. A required component of this machinery, SecA, contains an iron-binding domain, and disrupting the structure of this domain blocks the transport of proteins across the membrane in vivo. Our results suggest that this block is part of a physiological response to iron limitation since mutants that by-pass it are defective for adapting to growth under iron-limiting conditions. However, the physiological and molecular mechanisms behind this adaptive response are unknown. The student will use a powerful combination of modern molecular genetics, biochemistry and structural biology in order to investigate these mechanisms.

inhibits bacterial growth by inhibiting SecA, a component of the protein transport machinery. Azide appears to inhibit SecA by disrupting the structure of iron-binding domain in an otherwise non-essential region of the protein. his domain appears to sense iron changes in iron avail