New strategies to develop antibiotics for treatment of Pseudomonas aeruginosa and Leishmania spp infections.

The current available therapy against Pseudomonas aeruginosa and Leishmania spp infections for the well-known diseases such as cystic fibrosis and leishmaniasis (cutaneous, mucocutaneous and visceral) is far from satisfactory. It has been reported that established infections caused by P. aeruginosa are notoriously difficult to treat because this bacteria is usually resistant to many broad-spectrum antibiotics commonly used in hospitals and it may also acquire resistance to these drugs. Furthermore, a similar situation has been reported for leishmaniasis a complex of diseases caused by the protozoan parasite Leishmania spp in humans and dogs. In fact only a limited number of expensive drugs are available for the treatment of this disease and resistance to them is still increasing day by day in endemic regions. It is also well-known that antimicrobial peptides can play a very important role in host defense against these multi-drug resistant pathogens.

Hence, the aim of this six months project carried out at the Department of Chemistry Laboratories Durham University (UK) is firstly to find a synthetic peptide able to target the protein-protein interaction of an essential P. aeruginosa protein known as PA-Fur, and secondly to create a group of new anti-leishmanial synthetic peptides derived from natural AMPs (or antimicrobial peptides). To satisfy the targets of this double project a number of synthetic peptides were manufactured following a structure-based rational design and a selection of peptides from libraries with varying sequence composition were also synthesised. Synthetic peptides of this kind, with broad range activity and which might be produced industrially by chemical synthesis, have attracted the interest of many pharmaceutical companies as a possible new generation of antibiotics able to kill highly resistant pathogens. At present they have a realistic potential for overcoming the growing problems of antibiotic resistance.