| Summary: | 碩士 === 國立臺灣大學 === 醫學檢驗暨生物技術學研究所 === 95 === The worldwide rise of antibiotic resistance in bacteria has led to the development of new anti-microbial strategies. Photodynamic therapy (PDT) is one of the choices. Photodynamic therapy is based on the combination of photosensitizer, oxygen and harmless visible light to produce cytotoxicity via generation of reactive oxygen species.
We studied the photodynamic inactivation (PDI) effects of hematoporphyrin (Hp) and liposome-encapsulated-Hp (Lipo-Hp and polyethylene glycol (PEG) coating Lipo-Hp) on Group A streptococcus (GAS). PDI with 5 μM of Hp or Lipo-Hp followed by light irradiation of 90 J/cm2, resulted in more than 7.4 log killing for GAS. At the same concentration of photosensitizers (0.5μM), and light dose (90 J/cm2), PEG-Lipo-Hp attained 7.2 log killing and Lipo-Hp attained 4.4 log killing for GAS, but Hp only exhibited 0.3 log killing for GAS. The results showed that using lipo-Hp or PEG coating Lipo-Hp as photosensitizers can promote a more efficient photoinactivation of GAS. At the same time, we found out Hp-PDI reduced virulence factor- protease production of GAS.
We also studied the toluidine blue O (TBO) and rose bengal (RB) mediated PDI in clinical multidrug resistant bacteria such as vancomycin-resistant Enterococcus (VRE), multidrug-resistant Pseudomonas aeruginosa (MDRPA), and Acinetobacter baumannii. In this study, we show that of TBO-PDT is effective against all strains we used. PDI efficacies were independent of the antibiotic resistance pattern of the given microbial strains. At last, we used rapidly screening method to demonstrate the TBO-PDI activity in 33 multidrug resistant Pseudomonas aeruginosa and 19 susceptible Pseudomonas aeruginosa clinical isolates. We found that minimal lethal drug concentrations were not different between clinical multidrug resistant and susceptible bacteria strains.
Our studies have demonstrated that low dose liposome-encapsulated-Hp can enhance the photobactericidal activity of Hp on GAS, and its effect against antibiotic resistant bacteria was independent of their resistance pattern. These promising results suggest that PDI has the potential to be a possible alternative to antibiotic in clinical applications. In the future, we will focus on membrane proteins and nucleic acid damage during Hp-PDT on Group A streptococcus. We hope that we can better understand the mechanisms of photoinactivation for bacteria.
|
|---|
