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

• Published in: PloS one Vol. 12; no. 3; p. e0174627
• Main Authors: Zhang, Qing-Zhao, Zhao, Ke-Qing, Wu, Yang, Li, Xian-Hui, Yang, Chen, Guo, Li-Min, Liu, Chun-Hong, Qu, Di, Zheng, Chun-Quan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.03.2017; Public Library of Science (PLoS)
• Subjects: Aminolevulinic acid; Aminolevulinic Acid - administration & dosage; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Antibiotic resistance; Antibiotics; Antiinfectives and antibacterials; Bacteria; Bacterial infections; Biofilms; Biofilms - drug effects; Biofilms - radiation effects; Biology and Life Sciences; Combined treatment; Drug sensitivity testing; Experiments; Hospitals; Humans; Infections; Laboratories; Light emitting diodes; Medical research; Medicine; Medicine and Health Sciences; Microbial mats; Microbial Sensitivity Tests; Multidrug resistance; Otolaryngology; Patients; Photochemotherapy; Photodynamic therapy; Photosensitization; Physiological aspects; Properties; Research and Analysis Methods; Sensitivity analysis; Side effects; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - pathogenicity; Surgery; Toxicity; Virology; Yang Wu; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0174627

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.