(135d) Invited Speaker: Peptide-Based Approaches to Treating and Preventing Fungal Infections

Candida albicansis a commensal organism of humans that is also a frequent cause of disease in immunocompromised patients. Infections caused by C. albicansinclude oral infections like oral thrush and biofilm-associated infections on medical devices. Treating infections caused by C. albicanscan be challenging due to increasing drug resistance and the limited number of antifungal agents that are currently available. To address the current challenges associated with treating fungal infections, we are designing peptides capable of specifically targeting C. albicans. One of these peptides is histatin 5, an antimicrobial peptide found in human saliva that has potent and specific activity against C. albicans. Although histatin 5 has promise as a therapeutic agent, the fungus produces secreted aspartic proteases that degrade the peptide and reduce its antifungal activity. We have designed analogs of histatin 5 that offer strong resistance to the fungal proteases and improved antifungal activity. We are investigating the use of these analogs for treating and preventing Candida infections, including biofilm-associated infections, while also improving understanding of how the secreted aspartic proteases recognize and cleave peptide substrates. In addition to exploring peptides as potential therapeutics, we are also using peptides to target and deliver bioactive molecules to Candidapathogens. We are examining how properties of these cell-penetrating peptides affect their translocation across the cell wall and cell membrane of Candidacells and are defining the types of cargo they can carry into fungal cells. Our peptide-based strategies offer a new approach to designing antifungal therapeutics capable of treating and preventing fungal infections.