Chlorin e6 mediated photodynamic inactivation for multidrug resistant Pseudomonas aeruginosa keratitis in mice in vivo
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Published on: July 2, 2013
Ming-Feng Wu1,2, Mona Deichelbohrer3, Thomas Tschernig3
1Department of Ophthalmology, Saarland University Medical Center, Homburg/Saar, Germany.
Abstract:
Following corneal epithelium scratches, mouse corneas were infected with the multidrug resistant (MDR) P. aeruginosa strain PA54. 24 hours later, 0% (for control group), 0.01%, 0.05% or 0.1% Chlorin e6 (Ce6), a second generation photosensitizer derived from chlorophyll, was combined with red light, for photodynamic inactivation (PDI). 1 hour or 2 days later, entire mouse eyes were enucleated and homogenized for counting colony forming units (CFU) of P. aeruginosa. For comparison, 0.1% Ce6 mediated PDI was started at 12 hours post infection, and 0.005% methylene blue mediated PDI 24 hours post infection. Clinical scores of corneal manifestation were recorded daily. Compared to the control, CFU 1 hour after PDI started 24 hours post infection in the 0.01% Ce6 and 0.05% Ce6 groups were significantly lower (more than one log10 reduction), the CFU 2 days post PDI higher in the 0.1% Ce6 group, clinical score lower in the 0.1% Ce6 group at 1 day post PDI. These findings suggest that PDI with Ce6 and red light has a transient efficacy in killing MDR-PA in vivo, and repetitive PDI treatments are required to fully resolve the infection. Before its clinical application, the paradoxical bacterial regrowth post PDI has to be further studied.
Insights
Photodynamic inactivation (PDI) using Chlorin e6 (Ce6) and red light showed transient efficacy against multidrug-resistant Pseudomonas aeruginosa eye infections in mice, indicating a need for repeated treatments.
Area of Science:
- Ophthalmology
- Microbiology
- Photodynamic Therapy
Background:
- Multidrug-resistant (MDR) Pseudomonas aeruginosa poses a significant threat to ocular health, particularly after corneal injury.
- Photodynamic inactivation (PDI) is an emerging antimicrobial strategy utilizing photosensitizers and light to generate reactive oxygen species.
Purpose of the Study:
- To evaluate the efficacy of PDI with Chlorin e6 (Ce6) and red light in treating MDR P. aeruginosa keratitis in a mouse model.
- To compare the effectiveness of different Ce6 concentrations and treatment timings for PDI.
Main Methods:
- Mouse corneas were infected with MDR P. aeruginosa PA54 after epithelial scratches.
- Photodynamic inactivation was performed using varying concentrations of Ce6 (0.01%-0.1%) combined with red light at 24 hours post-infection.
- Bacterial load (CFU) and clinical scores were assessed at 1 hour and 2 days post-PDI. Comparative treatments included earlier Ce6-PDI (12 hours) and methylene blue-PDI (24 hours).
Main Results:
- PDI with 0.01% and 0.05% Ce6 significantly reduced bacterial CFU 1 hour post-treatment compared to controls.
- A paradoxical increase in CFU was observed in the 0.1% Ce6 group at 2 days post-PDI.
- The 0.1% Ce6 group showed lower clinical scores at 1 day post-PDI, suggesting initial therapeutic benefit.
Conclusions:
- PDI with Ce6 and red light demonstrates transient efficacy against MDR P. aeruginosa in vivo.
- Repetitive PDI treatments may be necessary for complete infection resolution.
- Further investigation into the mechanisms of bacterial regrowth post-PDI is crucial before clinical application.
