São Carlos Institute of Physics, University of São Paulo, São Carlos, Brazil.
Photochem Photobiol Sci. 2024 Jul;23(7):1323-1339. doi: 10.1007/s43630-024-00597-4. Epub 2024 May 28.
Mucormycosis is an extremely aggressive fungal disease with a high mortality rate, especially in people with compromised immune systems. Most cases of mucormycosis are caused by the fungus Rhizopus oryzae. The treatments used are based on high doses of antifungals, associated with surgical resections, when it is possible. However, even with this aggressive treatment, the estimated attributable mortality rate is high. There is therefore a need to develop adjuvant treatments. Photodynamic Inactivation (PDI) may be an auxiliary therapeutic option for mucormycosis. Due to the lack of reports in the literature on the morphology and photodynamic inactivation of R. oryzae, characterization of the fungus using Confocal Microscopy and Transmission Electron Microscopy, and different protocols using Photodithazine® (PDZ), a chlorin e6 compound, as a photosensitizer, were performed. The fungus growth rate under different concentrations and incubation times of the photosensitizer and its association with the surfactant Sodium Dodecyl Sulphate (SDS) was evaluated. For the hyphae, both in the light and dark phases, in the protocols using only PDZ, no effective photodynamic response was observed. Meanwhile with the combination of SDS 0.05% and PDZ, inhibition growth rates of 98% and 72% were achieved for the white and black phase, respectively. In the conidia phase, only a 1.7 log reduction of the infective spores was observed. High concentration of melanin and the complex and resistant structures, especially at the black phase, results in a high limitation of the PDI inactivation response. The combined use of the SDS resulted in an improved response, when compared to the one obtained with the amphotericin B treatment.
毛霉病是一种具有高死亡率的侵袭性真菌感染,尤其在免疫系统受损的人群中更为常见。大多数毛霉病是由根毛霉引起的。目前的治疗方法主要基于大剂量的抗真菌药物,并在可能的情况下结合手术切除。然而,即使采用这种积极的治疗方法,估计的病死率仍然很高。因此,需要开发辅助治疗方法。光动力失活(PDI)可能是毛霉病的辅助治疗选择。由于文献中缺乏关于根毛霉形态和光动力失活的报道,因此使用共聚焦显微镜和透射电子显微镜对真菌进行了表征,并使用 Photodithazine®(PDZ),一种叶绿素 e6 化合物作为光敏剂,进行了不同的方案。评估了不同浓度的光敏剂和其与表面活性剂十二烷基硫酸钠(SDS)孵育时间对真菌生长速度的影响。对于菌丝,在使用 PDZ 的光和暗相中,均未观察到有效的光动力反应。同时,在 SDS 0.05%和 PDZ 联合使用的方案中,白相和黑相的抑制生长率分别达到 98%和 72%。在孢子相中,仅观察到感染孢子的对数减少 1.7。高浓度的黑色素和复杂而坚固的结构,特别是在黑相,导致 PDI 失活反应的高限制。与两性霉素 B 治疗相比,联合使用 SDS 可提高反应效果。