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.
Highlights
Staphylococcus aureus (S. aureus) is a major cause of hospital-acquired and communityacquired pathogenic bacteria [1]
The 45 S. aureus strains of methicillin sensitive staphylococcus aureus (MSSA) (36) and methicillin resistant staphylococcus aureus (MRSA) (9) were collected after microbiologic characterization testing
We performed tests to exclude the toxicity of aminolevulinic acid (ALA) or light irradiation to S. aureus biofilm, respectively, to determine the parameters of the dose of the ALA and light irradiation used in our study
Summary
Staphylococcus aureus (S. aureus) is a major cause of hospital-acquired and communityacquired pathogenic bacteria [1]. Photodynamic therapy (PDT), an alternative to antibiotics for the treatment of bacterial infection, uses photosensitizers activated by the light of an appropriate wavelength. 5-aminolevulinic acid (ALA) is a prodrug that is converted to a natural photosensitizer, protoporphyrin IX (PpIX), in target cells [4]. ALA’s photodynamic effect is restricted to superficial lesions (1–2 mm) because of the limited penetration of the light source [7]. These characteristics may shorten light avoidance time, reduce tissue damage, and improve the efficacy of PDT, all of which ensure the safety and efficacy of PDT in clinical application
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