The efficacy of 5-aminolevulinic acid photodynamic therapy in inducing cell death in multidrug-resistant Trichophyton mentagrophytes: An in vivo and in vitro study.

BACKGROUND

Majocchi's Granuloma (MG) is manifested as the deep-seated, persistent suppurative granulomatous perifollicular inflammation. Traditional treatment for MG typically involves a combination of systemic oral antifungal drugs and topical medications; however, this approach often results in a low cure rate, high recurrence rate, and significant adverse effects. In contrast, 5-aminolevulinic acid photodynamic therapy (ALA-PDT), which has emerged as a novel strategy for treating fungal infections, is being increasingly utilized in the management of infectious granulomas.

METHODS

A patient with refractory MG caused by Trichophyton mentagrophytes (T. mentagrophytes) received three cycles of ALA-PDT. Additionally, a drug-resistant strain of T. mentagrophytes isolated from the patient's lesions was subjected to in vitro testing and evaluated in a guinea pig model to elucidate the mechanisms by which ALA-PDT exerts its inhibitory effects on the strain and other clinical and standard strains of T. mentagrophytes.

RESULTS

After three courses of ALA-PDT, the lesions were successfully eliminated. Both in vitro and in vivo experiments demonstrated that ALA-PDT significantly inhibited the growth of T. mentagrophytes. We further demonstrated that ALA or ALA-PDT treatment could enhance the sensitivity of T. mentagrophytes to subsequent traditional antifungal agent. When T. mentagrophytes was treated with ALA or ALA-PDT, the structural integrity of the fungal cells was directly disrupted. This disruption led to several observable effects: the integrity of the cell wall was compromised, pores rupture in the cell membrane, and swelling occurred in both the endoplasmic reticulum and mitochondria.

CONCLUSION

These findings suggest that ALA-PDT disrupts the cell membrane, cell wall and internal cellular structure of T. mentagrophytes through increasing the release of Reactive Oxygen Species (ROS), thereby facilitating the elimination of the fungus. This research highlights the therapeutic potential of ALA-PDT as an innovative strategy for managing fungal infections, particularly those resistant to conventional treatments.