Research overview

Understanding how bacteria cause disease is our primary goal. As well as being free-living, bacteria can live in complex communities called biofilms. We are working together to understand the formation, architecture and dispersal of biofilms in the environment and healthcare settings. We are interested in reducing these reservoirs of infection.

To do this, with Prof Paul Williams and Prof Morgan Alexander, we are working within an EU consortium lead by the National Institute of Physics to push the boundaries of a range of technological platforms including TOF-SIMS and Raman Microscopy to image biofilms and track the path of antibiotics within them. We are also monitoring the microfiches within biofilms with novel optical nanosensors in collaboration with Prof Jonathan Aylott.

We are also building up a large amount of preliminary data to enable us to study the process of bacterial colonization of human skin and extending this to the dynamics of polymicrobial biofilms encompassing both commensals and pathogens.

The novel virulence factor of P. aeruginosa that we characterised (AaaA) is proving to have a complex regulatory cascade and contribute to biofilm maintenance which we are unravelling. As part of this we have been localising the secretion pathway of this autotransporter in parallel with another (EspC). We are also investigating this in the context of acute and chronic respiratory infections with Profs Miguel Camara, Alan Smyth and Aras Kadioglu.

Our ultimate aim is to monitor the gene expression, protein production and metabolism of individual bacterial cells in real time.

We are particularly interested in secreted and cell surface proteins as they are ideally situated to help bacteria cause disease. These proteins can be used as weapons to attack the host. This enables the invading bacteria to disable the host’s immune system and also liberates nutrients that the bacteria can then use as fuel to grow and multiply. Cell surface proteins can also act as a physical barrier to prevent the immune system destroying the bacteria, or as a camouflage to disguise the invaders. In addition if they are ‘sticky’, cell surface proteins help the bacteria anchor themselves to the part of the host where they want to live. Moreover, some cell surface proteins can detect what chemicals are in their environment, thus directing the bacteria to the most favorable location for life. It is therefore not surprising that 20% of a bacterium’s proteins are secreted.

Secretion machinery components began to be discovered about 20 years ago, however we still do not know how they work. We are interested in finding this out because then we will be able to design novel antimicrobials to prevent and cure infectious diseases. We also want to know more about the functions of the secreted proteins that have not yet been characterized.

Since a successful infection will not only rely on the production of secreted proteins, but also depend on this being at the right time and in the right place, we study gene regulatory mechanisms. Primarily those used by bacteria to communicate with each other (quorum sensing). The main focus of this has been LuxS and AI-2, particularly asking how cells balance the function of LuxS as a central metabolic enzyme and the production of the small diffusible quorum sensing signal molecule AI-2.

To put this into real life context, we have been involved in some more translational projects, aimed at helping children wash their hands better so that the spread of infectious diseases is decreased. This is a cross-disciplinary project involving nurses, social scientists, learning science experts and engineers to design and build an interactive, educational toy called the Glo-yo. This has recently attracted the attention of the Press, and is a fun way for children to learn how to wash their hands. Thanks must go to the schools and children that helped design it (John Clifford Primary School, Meadow Lane Infants School, College House Junior School in Chilwell/Beeston, Nottingham). It was the concept of the undergraduate engineer (James Metcalf) who was supervised by Dr Joel Segal. We were able to address infection control using the expertise of Dr Jacqueline Randle (School of Nursing and Midwifery), hold well planned focus groups with the children because of the impact of learning Science with the help of Dr Caroline Windrum (LSRI), and assess the behavioural change using Social Science (Dr Helena Webb and Prof Brigitte Nerlich). Us microbiologists (Dina Lary and Jeni Luckett) monitor the number of microbes on the hands before and after use, and identify whether there are any particularly harmful ones (like superbugs or antibiotic resitant bacteria).

This work has been funded by British Society for Antimicrobial Therapy, Wellcome Trust, BBSRC, MRC, EPSRC, CNRS, Unilever, Roche, EU, Nottingham University Hospital trust and Nottingham University.