Abstract
Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, light and O2, 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.
Highlights
Microbial infections are still among the leading causes of death in the world, primarily because of the surfacing of pathogenic bacteria that have developed multidrug resistance (MDR) [1]
Among the photosensitizers potentially amenable to be used as an antimicrobial agent, 5-aminolevulinic acid (5-ALA) presents favorable characteristics [6,7]. 5-ALA is not a PS per se but, when it is taken up by target cells, it is metabolically changed to Protoporphyrin
The problem of bacterial antibiotic resistance is exacerbated by the strong tendency of pathogenic bacteria to form biofilms
Summary
Microbial infections are still among the leading causes of death in the world, primarily because of the surfacing of pathogenic bacteria that have developed multidrug resistance (MDR) [1]. Among these treatments, photodynamic therapy (PDT) has reemerged over the last decade because it proved effective against some antibiotic-resistant pathogenic bacteria [4]. Microbial infections sometimes appear to be more resistant to treatment because of the formation of biofilms. Such entities are a sort of multicellular communities, usually held together by a self-produced matrix in which cells are embedded within an extracellular polymeric substance (EPS) and adhere to each other and/or to a surface. PDT has been investigated for its ability to eradicate biofilms produced by bacteria infecting medical devices [12,13], its use, especially in combination with other approaches, has not been fully investigated as of yet. The treatment combines PDT with antibiotic therapy in order to achieve an additive or synergistic therapeutic effect
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