Development and Exploitation of Novel Antimocrobial Agents

The control of pathogens can be achieved by the exploitation of naturally occurring antimicrobial agents. We will continue to develop established research on lantibiotics and bacteriophage endolysins. With respect to lantibiotics we will isolate novel molecules from nature using new molecular screening approaches and perfect existing structures by peptide engineering. There are new opportunities to apply this approach to nisin, which remains a potent antimicrobial lantibiotic and one in which we have extensive experience. We will develop the potential of bacteriophage endolysins. The immediate focus will be on the cloning and characterisation of new endolysins that are active against clostridia. We will investigate their potential in the context of the gastrointestinal tract, with the intention of controlling disease states caused by Clostridium perfringens and Clostridium difficile. We will build on our strengths in the exploitation of lactic acid bacteria as GI tract delivery vehicles for antigens. <P>
This approach offers a range of biotechnological opportunities with enormous potential to address infectious disease and allergy. We will build on recent successes with a model system involving a pneumococcus antigen and complete work on the expression of a viral antigens. The established impact of Lactococcus on the immune response will be investigated at the level of both host cell gene expression and the role of the lactococcal genome. In addition, recombinant lactic acid bacteria offer a powerful investigative approach with which to analyse interactions between the host and the microflora at a molecular level. The cross talk between GI tract bacteria and the host immune system will be probed focussing initially on the interplay between lactic acid bacteria and dendritic cells. This involves interaction with other projects within the IFR portfolio.