Antimicrobial Biophotonic Treatment of Ampicillin-Resistant Pseudomonas aeruginosa with Hypericin and Ampicillin Cotreatment Followed by Orange Light

Abstract

Bacterial antibiotic resistance is an alarming global issue that requires alternative antimicrobial methods to which there is no resistance. Antimicrobial photodynamic therapy (APDT) is a well-known method to combat this problem for many pathogens, especially Gram-positive bacteria and fungi. Hypericin and orange light APDT efficiently kill <i>Staphylococcus aureus</i>, methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), and the yeast <i>Candida albicans</i>. Although Gram-positive bacteria and many fungi are readily killed with APDT, Gram-negative bacteria are difficult to kill due to their different cell wall structures. <i>Pseudomonas aeruginosa</i> is one of the most important opportunistic, life-threatening Gram-negative pathogens. However, it cannot be killed successfully by hypericin and orange light APDT. <i>P. aeruginosa</i> is ampicillin resistant, but we hypothesized that ampicillin could still damage the cell wall, which can promote photosensitizer uptake into Gram-negative cells. Using hypericin and ampicillin cotreatment followed by orange light, a significant reduction (3.4 log) in <i>P. aeruginosa</i> PAO1 was achieved. <i>P. aeruginosa</i> PAO1 inactivation and gut permeability improvement by APDT were successfully shown in a <i>Caenorhabditis elegans</i> model.