Molecular cell biology of metals and bacterial pathogenicity

Bacterial infectious diseases remain a leading cause of death worldwide. With the continuing increase in antibiotic-resistant bacteria, new strategies are urgently needed to both treat bacterial diseases and prevent tansmission. Metals such as iron, copper, zinc and manganese play a central role in the outcome of bacteria-host interactions. To control infections, in a process termed nutritional immunity, the immune system exploits the need for bacteria to acquire metals to proliferate and also the innate toxicity of metals. In response, pathogenic bacteria have evolved a myriad of metal-handling systems that allow them to obtain enough of the metals they need in different environments whilst avoiding metal toxicity. The bacterial proteins that make up these systems represent key virulence factors and are attractive targets for antimicrobial drug development. Targetting these proteins may not only help to treat disease but also control and bacterial pathogens during food production and storage and within clinical, agricultural and domestic settings.  My research group is uncovering and characterising these systems and analysing their roles in the sensing, acquisition, export, intracellular distribution and storage of metals. The objectives of my research are to understand:

1. the molecular mechanisms responsible for metal homeostasis and ensuring that the correct metals bind to the correct proteins in bacteria.
2. their roles in allowing bacterial pathogens to sense and respond to metal stresses encountered in different environments, both inside and outside the host.
3. their contributions to pathogenicity and protecting against host immune defences. 

The current main projects are focussing on the food-borne pathogens Salmonella enterica serovar Typhimurium. Listeria monocytogenes and Campylobacter jejuni. Other collaborative research is involved in structure-based drug development against the causative agent of tuberculosis, Mycobacterium tuberculosis.

Impact:

Bacterial proteins involved in handling metals represent attractive targets for the development of anti-microbial drugs that target and inactivate these metal-handling systems.

Knowledge of the metal-challenges faced by bacterial pathogens within a host as well as their survival strategies will contribute to the development of next generation drugs that exploit nutritional immunity.

Due to the dependence of so many biological activities being dependent upon metals, a half of all enzymes requiring metals for catalysis, our research in understanding how metal availability is controlled within cells also has broad applications in biotechnology.

Roles & responsibilities:

Programme Director: BSc/MSci Microbiology

Chair of the Pathogens GM/Bio Safety Committee for FBMH

Unit coordinator and lecturer: BIOL21192, Principles of infectious disease

Lecturer: BIOL31362, Bacterials infections of man and BIOL31602 Toxins, toxicants and toxicity