4.7 Article

Photodynamic and Antibiotic Therapy in Combination to Fight Biofilms and Resistant Surface Bacterial Infections

Journal

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 16, Issue 9, Pages 20417-20430

Publisher

MDPI
DOI: 10.3390/ijms160920417

Keywords

photodynamic therapy; 5-aminolevulinic acid; Gentamicin; combination therapy

Funding

  1. Italian Ministry of University (Project Fondo per gli Investimenti della Ricerca di Base/Medical Research in Italy National Research Council (Firb/MERIT CNR)) [RBNE08YYBM_002]
  2. Italian Ministry of University (Project Fondo per gli Investimenti della Ricerca di Base/Medical Research in Italy National Research Council (project TUFO-Strategie e Prodotti per la Prevenzione, la Diagnosi Precoce. [PON01_02433]
  3. Programma Operativo regionale (POR) Campania Fondo Sociale Europeo (FSE) Campania Research in Experimental MEdicine (CREME)

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Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, light and O-2, has been principally considered for the treatment of specific types of cancers, other applications exist, including the treatment of infections. Unfortunately, PDT does not always guarantee full success since it exerts lethal effects only in cells that have taken up a sufficient amount of photosensitizer and have been exposed to adequate light doses, conditions that are not always achieved. Based on our previous experience on the combination PDT/chemotherapy, we have explored the possibility of fighting bacteria that commonly crowd infected surfaces by combining PDT with an antibiotic, which normally does not harm the strain at low concentrations. To this purpose, we employed 5-aminolevulinic acid (5-ALA), a pro-drug that, once absorbed by proliferating bacteria, is converted into the natural photosensitizer Protoporphyrin IX (PpIX), followed by Gentamicin. Photoactivation generates reactive oxygen species (ROS) which damage or kill the cell, while Gentamicin, even at low doses, ends the work. Our experiments, in combination, have been highly successful against biofilms produced by several Gram positive bacteria (i.e., Staphylococcus aureus, Staphylococcus epidermidis, etc.). This original approach points to potentially new and wide applications in the therapy of infections of superficial wounds and sores.

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