As multidrug resistant infections become more commonplace, Antimicrobial Photodynamic Therapy (AMPT) has gained increased attention due to its lower ability to elicit bacterial resistance. While many photosensitisers excel at eradicating gram-positive bacterial infections, they are often much less potent when utilized on negative bacteria. Difficulties in targeting gram-negative bacteria are primarily due to the poor ability of photosensitizers crossing and/or binding to the double membrane of gram-negative bacteria.<br/>To deal with the aforementioned limitation, our previous work focused on the conjugation of buforin II (a DNA targeting, antimicrobial cell penetrating peptide) to the well-known photosensitizer ruthenium(II) tris bipyridine. Specifically, buforin II allowed for increased cell penetration and targeting of the photosensitizer to DNA. A decrease in the minimum inhibitory concentration was used to confirm an increase in efficacy of the peptide ruthenium conjugate (Ru Buf II). Laser confocal microscopy showed an increased build up of Ru Buf II in gram negative cells when compared to unconjugated Ru(II) tris bipyridine that were tested at the same concentrations. Plasmid degradation assays pointed to an increased rate of DNA damage being responsible for the higher efficacy of Ru Buf II.   <br/>Our current objective is to expand conjugation of ruthenium(II) tris bipyridine to peptides with different mechanisms of action, including membrane targeting, cell penetrating, internal targets, and peptides displaying a combination of the mentioned mechanisms. Additionally, we are investigating other ruthenium based photosensitizers for conjugation in an effort to further optimize antimicrobial efficacy.

Antimicrobial peptide-ruthenium conjugates as efficient photosensitizers for the inactivation of microbial pathogens

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.