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. 2010 Jan;42(1):38-44.
doi: 10.1002/lsm.20887.

Photodynamic therapy for methicillin-resistant Staphylococcus aureus infection in a mouse skin abrasion model

Tianhong Dai  1 , George P Tegos, Timur Zhiyentayev, Eleftherios Mylonakis, Michael R Hamblin
Affiliations

Photodynamic therapy for methicillin-resistant Staphylococcus aureus infection in a mouse skin abrasion model

Tianhong Dai et al. Lasers Surg Med. 2010 Jan.

Abstract

Background and objective: Methicillin-resistant Staphylococcus aureus (MRSA) skin infections are now known to be a common and important problem in the Unites States. The objective of this study was to investigate the efficacy of photodynamic therapy (PDT) for the treatment of MRSA infection in skin abrasion wounds using a mouse model.

Study design/materials and methods: A mouse model of skin abrasion wound infected with MRSA was developed. Bioluminescent strain of MRSA, a derivative of ATCC 33591, was used to allow the real-time monitoring of the extent of infection in mouse wounds. PDT was performed with the combination of a polyethylenimine (PEI)-ce6 photosensitizer (PS) and non-coherent red light. In vivo fluorescence imaging was carried out to evaluate the effect of photobleaching of PS during PDT.

Results: In vivo fluorescence imaging of conjugate PEI-ce6 applied in mice indicated the photobleaching effect of the PS during PDT. PDT induced on average 2.7 log(10) of inactivation of MRSA as judged by loss of bioluminescence in mouse skin abrasion wounds and accelerated the wound healing on average by 8.6 days in comparison to the untreated infected wounds. Photobleaching of PS in the wound was overcome by adding the PS solution in aliquots.

Conclusion: PDT may represent an alternative approach for the treatment of MRSA skin infections.

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Figures

Fig. 1
Fig. 1
Mouse model of skin abrasion.
Fig. 2
Fig. 2
A: Successive fluorescence images of conjugate PEI–ce6 in a mouse given a single 20 μl aliquot on the back during PDT. B: Successive fluorescence images of conjugate PEI–ce6 applied in a mouse with multiple aliquots of 20, 10, 10, and 10 μl at the time points when 0, 24, 48, 72 J/cm2 light had been delivered during PDT. C: Remaining fractions of fluorescence of conjugate PEI–ce6 in the mice noted in A and B.
Fig. 3
Fig. 3
A: Successive bioluminescence images of a representative mouse skin abrasion wound infected with luminescent MRSA. B: A Gram-stained section of a mouse skin abrasion specimen showing the bio-films formed by Gram-positive MRSA near the skin surface. Dark blue area: bio-films of MRSA. The mouse skin abrasion specimen was harvested at day 3 post-infection.
Fig. 4
Fig. 4
A: Dose–response of bacterial luminescence of a mouse abrasion wound infected with MRSA and treated with PDT; and dose–response of bacterial luminescence of a mouse abrasion wound infected with MRSA and treated with conjugate PEI–ce6 only. PDT was carried out at 30 minutes after infection. B: Dose–response of mean bacterial luminescence of the mouse wounds infected with MRSA and treated with PDT (n = 10). C: Time courses of bacterial luminescence of the infected abrasion wounds in the PDT-treated mice (n = 10) and non-treated mice (n = 12). D: Mean areas under the bioluminescence versus time plots (in the two-dimensional coordinate system in (C), representing the overall bacterial burden of mouse abrasion wounds in different groups. Bars: standard deviation.
Fig. 5
Fig. 5
A: Kaplan–Meier wound healing curves of MRSA infected mouse abrasion wounds without treatment (neither PS nor light was applied) and treated with PDT, respectively. B: Wound morphologies at day 4 post-infection of a representative PDT-treated mouse wound and a non-treated mouse wound.
Fig. 6
Fig. 6
Time courses of the mean normalized body weight of PDT-treated mice and non-treated mice over 4 days post-infection. Bars: standard deviation.
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