Hypericin and Pheophorbide a Mediated Photodynamic Therapy Fighting MRSA Wound Infections: A Translational Study from In Vitro to In Vivo

Abstract

High prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA) and lack of effective antibacterial treatments urge discovery of alternative therapeutic modalities. The advent of antibacterial photodynamic therapy (aPDT) is a promising alternative, composing rapid, nonselective cell destruction without generating resistance. We used a panel of clinically relevant MRSA to evaluate hypericin (Hy) and pheophobide a (Pa)-mediated PDT with clinically approved methylene blue (MB). We translated the promising in vitro anti-MRSA activity of selected compounds to a full-thick MRSA wound infection model in mice (in vivo) and the interaction of aPDT innate immune system (cytotoxicity towards neutrophils). Hy-PDT consistently displayed lower minimum bactericidal concentration (MBC) values (0.625–10 µM) against ATCC RN4220/pUL5054 and a whole panel of community-associated (CA)-MRSA compared to Pa or MB. Interestingly, Pa-PDT and Hy-PDT topical application demonstrated encouraging in vivo anti-MRSA activity (>1 log10 CFU reduction). Furthermore, histological analysis showed wound healing via re-epithelization was best in the Hy-PDT group. Importantly, the dark toxicity of Hy was significantly lower (p < 0.05) on neutrophils compared to Pa or MB. Overall, Hy-mediated PDT is a promising alternative to treat MRSA wound infections, and further rigorous mechanistic studies are warranted.

The Restorative Effect of Titanium Dioxide Nanoparticles Synthesized with Origanum vulgare L., Carvacrol, Hypericum perforatum L., and Hypericin Loaded in Calcium Alginate Scaffold on Staphylococcus aureus-Infected Ulcers in Diabetic Rats

“…their study also showed the inhibitory influence of H. perforatum on different types of S.aureus (Nostro et al, 2007). ated PDT is an effective therapeutic option against MRSA (Chan et al, 2021). By their study, our results also showed the effectivity of Hypericin on the wound healing process in S.aureus infected skin.…”

In Vivo Quantification of the Effectiveness of Topical Low-Dose Photodynamic Therapy in Wound Healing Using Two-Photon Microscopy

“…The phototherapy of wounds is closely related to the problem of infectious disease treatment, especially in the presence of antibiotic-resistant bacteria in the bacterial biofilms covering the wound surface [35,59]. Since the development of antibacterial drugs is not keeping pace with microbial resistance, it is necessary to use alternative antibacterial approaches, including antimicrobial PDT.…”

The role of the light source in antimicrobial photodynamic therapy

“…Due to heat generation, lamps require a cooling element (water tank or ice), commonly assembled between the light source and irradiated sample. 408,409,413,442–444 Heating is much less of a problem for LEDs because of their much higher efficiency. Lasers, as the most common light source are characterized by the broadest range of power output values.…”