title: 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.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Eye & ENT Hospital, School of Shanghai Medicine, Fudan University, Shanghai, PR China.
authors.forename: Qing-Zhao
authors.initials: QZ
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Eye & ENT Hospital, School of Shanghai Medicine, Fudan University, Shanghai, PR China.
authors.forename: Ke-Qing
authors.initials: KQ
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Science and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Eye & ENT Hospital, School of Shanghai Medicine, Fudan University, Shanghai, PR China.|Department of Otolaryngology, Ruijin Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Eye & ENT Hospital, School of Shanghai Medicine, Fudan University, Shanghai, PR China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Guo
authors.affiliation: Department of Clinical Laboratory, Eye and ENT Hospital, Fudan University, Shanghai, China.
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Science and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Di
authors.initials: D
authors.lastname: Qu
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Eye & ENT Hospital, School of Shanghai Medicine, Fudan University, Shanghai, PR China.
authors.forename: Chun-Quan
authors.initials: CQ
authors.lastname: Zheng
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D010778:Photochemotherapy; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D000622:Aminolevulinic Acid