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

Date Published: March 30, 2017

Publisher: Public Library of Science

Author(s): Qing-Zhao Zhang, Ke-Qing Zhao, Yang Wu, Xian-Hui Li, Chen Yang, Li-Min Guo, Chun-Hong Liu, Di Qu, Chun-Quan Zheng, Michael Hamblin.

http://doi.org/10.1371/journal.pone.0174627

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.

Partial Text

Staphylococcus aureus (S. aureus) is a major cause of hospital-acquired and community-acquired pathogenic bacteria [1]. Its ability to form biofilm makes it difficult to be eradicated by the human immune system and traditional treatments, namely antibiotics [2]. It has become imperative to develop alternative approaches to manage biofilm infections.

The administration of exogenous ALA leads to the accumulation of PpIX and induces cellular damage or death after light irradiation by the produced ROS [16]. ALA-PDT has been proven to effectively treat planktonic antibiotic resistant strains [5]. However, contrary to its planktonic counterpart, the sessile structure of the biofilm makes it more difficult to be eradicated. To the best of our knowledge, the studies of ALA-PDT on S. aureus biofilm are extremely limited [17,18].

 

Source:

http://doi.org/10.1371/journal.pone.0174627

 

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