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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.

Mostra/Nascondi contenuto.
6 | P a g e 1.0 INTRODUCTION 1.1 Pseudomonas aeruginosa The name of the genus Pseudomonas means false unit: the word pseudo ( ψευδ ο) comes from Greek and means false and the word monas comes from Latin (monas) and from Greek ( μονος) and means a single unit. The name of the species aeruginosa is a word coming from Latin and its meaning is copper rust, this also describes the blue-green pigment that the bacteria produces in laboratory cultures. This pigment is a combination of two metabolites, the green is due to pyoverdine and the blue to pyocyanin, they give to this bacteria its characteristic color appreciated in its cultures. 1-9, 17 [1] [2] Figure1. Medium sized grey or bluish colonies. In areas of confluent growth the colonies and agar are dark due to production of the pigments pyoverdin and pyocyanin. Figure2. P. aeruginosa bacterial culture on an Xylose Lysine Sodium Deoxycholate (XLD) agar plate. Pseudomonas aeruginosa is an aerobic Gram-negative rod, widely distributed in nature, motile by means of polar flagella, it is able to utilize a very wide range of carbon and energy sources and to grow over a wide temperature range, but not anareobically. During its growing it produces irregular irridescent colonies and a characteristic smell, it also produces this soluble blue-green pigmentation (pyocyanin and pyoverdin). This bacteria is oxidase positive and oxidative in the Hugh and Liefson test. 1-9,18

Tesi di Laurea Magistrale

Facoltà: Farmacia

Autore: Alessandra Piccitto Contatta »

Composta da 63 pagine.

 

Questa tesi ha raggiunto 107 click dal 04/04/2012.

Disponibile in PDF, la consultazione è esclusivamente in formato digitale.