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(BBSRC DTP) Metals and bacterial virulence: overcoming metal intoxication during infection

Project Description

Campylobacter jejuni is a globally important food-borne pathogen, being the leading bacterial cause of human acute gastroenteritis and responsible for an estimated 0.5 billion cases each year. This bacterium is able to colonize and persist in farm animals, particularly chickens, which are the major source of human campylobacteriosis. The public health significance of campylobacteriosis underlines the urgent need for new strategies to reduce infections, yet the mechanisms employed by C. jejuni to persist within the food chain and to colonise and infect its hosts are relatively poorly understood. Transition metals, such as zinc and copper, are known to play a central role in the outcome of bacteria-host interactions. To control infections the immune system exploits the need for bacteria to acquire these metals to proliferate, by restricting their availability in a process termed ‘nutritional immunity’, as well as the innate metal toxicity, by poisoning bacteria with antimicrobial concentrations. In response, pathogenic bacteria have evolved a myriad of metal-sensing, metal-acquisition and metal-detoxification systems that act to maintain metal homeostasis and represent key virulence determinants. This project will build on our previous work focussing on metals at the host-pathogen interface and will combine the expertise of three laboratories (Cavet – Metal handling in bacterial pathogens, Linton – Campylobacter biology and Lloyd – Metal reduction and metallic nanoparticle synthesis) in order to uncover and characterise the metal handling systems in C. jejuni. This will involve examining the factors associated with their regulation as well as examining their roles in allowing this pathogen to adapt to metal stress, including during the colonisation and infection of its animal and human hosts. In addition, with regard to the potential of metallic nanoparticles being exploited for their antimicrobial properties during food processing, the project will also seek to examine the roles of these metal handling systems in protecting against the antimicrobial activity of bacterially synthesised metallic nanoparticles. The initial focus will be on the characterisation of a recently identified C. jejuni virulence-associated operon that is linked to zinc and copper resistance. The project will involve a multidisciplinary approach that interfaces microbiology, infection biology, biochemistry, nanotechnology and chemistry. Proteins involved in handling metals represent attractive targets for the development of much needed novel antimicrobial agents and knowledge of how the metal homeostatic systems in C. jejuni contribute to survival within the food chain and its human and animal hosts will help inform future control strategies.

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

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