Studio di metaboliti coinvolti nei meccanismi di QS (quorum sensing) e QQ (quorum quenching) in microorganismi estremofili e loro applicazione nella terapia antimicrobica.

Cystic Fibrosis (CF) is a genetic disease seen in lungs, intestines, pancreas and sweat glands, and affects respiratory and digestive systems through elevated viscosity of fluids. Particular effects on respiratory systems might be life-threatening due to decreased pulmonary functions. Pseudomonas aeruginosa is presented as the main cause for high mortality and morbidity rates. Several antibiotics are utilized in CF for repressing chronic infections via colonization of P. aeruginosa. However, it is known that medical treatments are not efficient in some conditions. Some studies suggest that failure to remove disease might be caused by biofilm form of P. aeruginosa resistant to antibiotics. Biofilm is a complex that bacteria forms, in which they communicate by Quorum Sensing (QS) when they reach a certain population and show increased resistance. It is reported that the bacteria species live in the biofilm forms are up to 1000-3000 times more resistant to antibiotics compared to same species in planktonic form. Various studies foresee that specific biofilm production antagonists or agents alter the physical and biochemical properties of P. aeruginosa. Quorum sensing is the term adopted to describe the mechanism by which microbial communities coordinate gene expression at high cell density. QS mechanism regulates a variety of vital functions such as motility, growth inhibition, biofilm development, virulence expression and plasmid conjugation. Many of these activities are essential for the well-being of organisms, in particular in extreme conditions as hypersaline and high temperature environments. Halophiles and thermophiles are able to synthesize products that are stable and exploit their activities under such "extreme" conditions that mimic industrial processes. The versatility of these products lead researchers to address their interest to their biotechnological applications. To date, different kinds of autoinducers were detected in microorganisms (diketopiperazines, N-Acyl homoserine lactones, autoinducer-2), but the role of QS in the extremophiles (Archaea and Bacteria) needs to be elucidated yet. The main objective of this project is to discover Extremophilic microorganisms' secondary metabolites and enzymes that may be effective in the treatment of cystic fibrosis by inhibiting the communication and biofilm formation of Pseudomonas aeruginosa. The project will encourage multidisciplinary work by gathering different sub-disciplines together (microbiology, biochemistry, bacteriology, biophysics etc.). Also the collaboration with Italy will also contribute to the intellectual leadership of the project teams, which is included in CNR's and TÜB?TAK's priority aims. This collaboration project is a pioneer and innovative study due to the utilization of Extremophiles as sources of active metabolites. With utilization of secondary metabolites and enzymes, it is foreseen that dependence on foreign sources will reduce and the competing strength of our countries in scientific and industrial areas will increase. Moreover, the expertise of both team in the study of Extremophiles and natural products from microorganisms, including compounds involved in QS and QQ mechanisms, will be a good start point for a successful project.