5-aminolevulinic acid-mediated photodynamic therapy and its strain-dependent combined effect with antibiotics on Staphylococcus aureus biofilm

Abstract

Staphylococcus aureus (S. aureus) is hard to be eradicated, not only due to the emergence of antibiotic resistant strains but also because of its ability to form biofilm. Antibiotics are the major approach to treating biofilm infections, but their effects are unsatisfactory. One of the potential alternative treatments for controlling biofilm infections is photodynamic therapy (PDT), which requires the administration of photosensitizer, followed by light activation. 5-aminolevulinic acid (ALA), a natural photosensitizer prodrug, presents favorable characteristics, such as easy penetration and rapid clearance. These advantages enable ALA-based PDT (ALA-PDT) to be well-tolerated by patients and it can be repeatedly applied without cumulative toxicity or serious side effects. ALA-PDT has been proven to be an effective treatment for multidrug resistant pathogens; however, the study of its effect on S. aureus biofilm is limited. Here, we established our PDT system based on the utilization of ALA and a light-emitting diode, and we tested the effect of ALA-PDT on S. aureus biofilm as well as the combined effect of ALA-PDT and antibiotics on S. aureus biofilm. Our results showed that ALA-PDT has a strong antibacterial effect on S. aureus biofilm, which was confirmed by the confocal laser scanning microscope. We also found that lethal photosensitization occurred predominantly in the upper layer of the biofilm, while the residual live bacteria were located in the lower layer of the biofilm. In addition, the improved bactericidal effect was observed in the combined treatment group but in a strain-dependent manner. Our results suggest that ALA-PDT is a potential alternative approach for future clinical use to treat S. aureus biofilm-associated infections, and some patients may benefit from the combined treatment of ALA-PDT and antibiotics, but drug sensitivity testing should be performed in advance.

Properties of halogenated and sulfonated porphyrins relevant for the selection of photosensitizers in anticancer and antimicrobial therapies

“…Current progress in the development of photosensitizers relies on the identification of specific design parameters. On one hand, there is an increasing appreciation of the need to integrate in molecular design insights emerging from studies of PS-target interactions, cellular signaling processes and increased resistance [ 6 , 7 ]. On the other hand, photophysical and photochemical properties of PS can be related with its behavior in biological systems, namely with aggregation, tumor type-specific PS uptake mechanisms, binding to plasma proteins or change in hydrophilicity/lipophilicity in given physiological environments.…”

Xanthene Dyes and Green LED for the Inactivation of Foodborne Pathogens in Planktonic and Biofilm States

“…efflux systems), changes in the chemical microenvironment within the biofilm and even deactivation of antimicrobial agents . In addition, the reduced diffusion or neutralization of ROS by the biofilm matrix is known to decrease the penetration of light and PS to the bottom layers of biofilm , and the insufficient supply of oxygen in these deeper biofilm layers during aPDT is also suggested to play an important role in the tolerance of sessile cells to photoinactivation.…”

Combined Antimicrobial Activity of Photodynamic Inactivation and Antimicrobials–State of the Art

“…The combined treatment with ciprofloxacin and both lasers was effective against S. aureus biofilms, reducing the biofilm cell counts by 81% from its value for untreated cells and by 44% from its value for cells receiving monotherapy with ciprofloxacin (Krespi et al, 2011 ). In other studies, Barra et al ( 2015 ) and Zhang et al ( 2017 ) presented results of experiments which were conducted with the presence of delta- aminolevulinic acid and antibiotics against S. aureus . Barra et al ( 2015 ) reported a synergistic effect from the use of a combined aPDI and gentamycin treatment against three representatives belonging to Staphylococcus .…”