Ricerc@Sapienza

Respiratory infections associated to bacteria, yeasts, filamentous fungi or to viruses represent a serious life threat, especially in the elderly or in cystic fibrosis (CF) sufferers. This is mainly due to the increasing resistance of these pathogens to commonly-used drugs and, in the case of bacteria and fungi, to their ability to grow in a sessile community (biofilm) that traditional antibiotics/antimycotics are not able to eradicate. In addition, the presence of a compromised immune system related to age, including deficiency of vitamin D (Vd), contributes to the establishment of such infections. Antimicrobial peptides (AMPs) hold promise for the generation of new therapeutics.
Recently, we discovered that the amphibian skin AMPs esculentins and temporins kill both the planktonic and biofilm forms of reference strains of Pseudomonas aeruginosa/Staphylococcus aureus/Candida albicans with a membranolytic mode of action limiting the induction of resistance, while promoting wound healing of the bronchial epithelium. In addition, temporins were found to display a clear activity against the enveloped virus Herpes simplex. However, very little is known about the activity of these AMPs against filamentous fungi or viral species causing infections in the lung of elderly and CF patients.
Hence, with the purpose to develop these AMPs for clinical use as novel therapeutics with antibiotic/antifungal/antiviral and wound healing activities we will conduct: (i) further research studies on their virucidal potency against the most representative viral strains in the respiratory tract (ii) advanced analysis of their activity on a panel of clinical isolates and under physiopathological conditions (iii) an investigation of a potential synergistic effect in combination with conventional drugs and (iv) preclinical studies to evaluate the in vivo safety and efficacy of AMPs in reducing lung microbial/viral load also during Vd deficiency. All these goals fall within the Project aims.