ANTIMICROBIAL PEPTIDES AND THEIR INTERACTION WITH CANDIDA ALBICANS: MECHANISMS AND IMPLICATIONS

For the last decade, the WHO has highlighted the significant increase in antibiotic resistance and how this trend is compromising the treatment of common infectious diseases. They estimate that by 2050, deaths related to this issue will surpass those caused by cancer. Antimicrobial peptides (AMPs) form the first line of defense against infectious pathogens within the immune response. Due to their unique physical-chemical-biological profiles, AMPs are emerging as promising therapeutic agents for both human and animal health.
To develop a successful biomolecule as a tool for diagnosing and/or controlling diseases, we need to further understand the mechanisms of action employed by these molecules. We analyzed the interaction between a plant defensing-type peptide, identified from Erythrina crista-galli (EcgDF1), against the cells from the pathogen Candida albicans.
Raman confocal microscopy has been successfully used to elucidate complex biological system interactions. This tool has allowed us to further study the changes induced by the peptides by contrasting the output profiles, resulting in several biomolecules being overshadowed by the direct interaction with the peptide. The data analysis revealed the functional groups and chemical bonds involved in those interactions.
We conducted a biophysical characterization of recombinant EcgDF1 (47 amino acids) and six small synthetic variants (10-14 amino acids) derived from the full recombinant peptide. Our studies also focused on their interaction with C. albicans to elucidate the structural changes these peptides induce within the target cell. We identified the cell wall, cell membrane and intracellular molecules, such as cytochromes and nucleic acids, as the primary sites of interaction. Additionally, we characterized the peptides-DNA interaction using circular dichroism (in vitro). These results showed that all the small variants are capable of interacting and modifying the DNA structure to some extent. In contrast, EcgDF1 displayed no interaction whatsoever. By cross-referencing this data with their antimicrobial activity profiles, we could elucidate the mechanism of action of each peptide and attribute it to their effectiveness against C. albicans.