The chronic infections that develop in the airways of people with cystic fibrosis (CF) are mostly characterized by the presence of specialized, complex and heterogeneous polymicrobial communities, whose interaction is decisive on the clinical outcome of pulmonary infections in CF. Furthermore, due to the extensive and uncontrolled use of antibiotics, these microorganisms have adapted enormously and have become resistant to treatment with most drugs available today.
The response to this emergency is therefore the development of alternative therapies, such as those based on the use of anti-virulence agents capable of decreasing the pathogenicity of bacteria rather than counteracting their growth and survival as traditional antibiotics do.
This project will take into consideration two of the main pathogens, Pseudomonas aeruginosa (Pa) and Staphylococcus aureus (Sa) which frequently co-colonize the airways of people with CF.
The aims of the project are i) to evaluate the antimicrobial efficacy of two compounds, previously synthetized by the researchers, on murine models of Pa-Sa co-infection. The two compounds are structurally similar to each other, but act through a different mechanism of action; they have already shown antibacterial activity on murine models of acute and chronic lung mono-infection with Pa. Furthermore, ii) to evaluate whether the administration of their combination on mono-infection and co-infection models can result in an additive or synergistic effect. Treatments and analysis will be conducted in collaboration with the FFC Ricerca CFaCore.
The development of alternative antibacterial strategies, which do not subject pathogens to the selective pressure causing resistance, is fundamental for improving the clinical course of people with CF.