Davies A, Gebremedhin S, Yee M, Padilla R J, Duzgunes N, Konopka K, Dorocka-Bobkowska B
Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA, USA.
Department of Diagnostic Sciences, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
J Physiol Pharmacol. 2016 Oct;67(5):777-783.
The formation of biofilms by Candida and the increasing resistance of Candida species to antifungals contribute to the high recurrence rates of denture stomatitis. This increase has stimulated an interest in antimicrobial photodynamic therapy (aPDT) as an alternative treatment. We examined the photoactivity of the porphyrin-based photosensitizer, TMP-1363, against biofilms of C. albicans, C. glabrata, C. tropicalis and C. parapsilosis, and the effect of the combined use of miconazole and aPDT. Biofilms of three American Type Culture Collection (ATCC) strains and four clinical isolates developed on poly(methyl methacrylate) (PMMA) disks, were incubated with miconazole, followed by treatment with TMP-1363 for 30 min at 37°C. The plates were exposed to broadband visible light at a distance of 10 cm to the plate, for 30 min (irradiance at the surface of the plate: 32.5 mW/cm2). The metabolic activity of the biofilms was measured by the XTT assay. ATCC strains and C. glabrata 7531/06 were not sensitive to TMP-aPDT, whereas the metabolic activities of the remaining three clinical isolates were reduced to 64.2 ± 5.5% of controls. Miconazole at 25 μg/ml decreased the viability of all strains except the ATTCC strain C. albicans MYA274; however its combination with aPDT was effective against this strain, suggesting a synergistic interaction. Effects of miconazole and aPDT on C. albicans MYA 2732, C. albicans 6122/06 were additive. With C. tropicalis and C. parapsilosis, the combined treatment had a higher, but not entirely additive, cytotoxic effect. The combined use of miconazole and TMP-aPDT is advantageous in the treatment of biofilms of a number of Candida species and strains, but not all. The molecular basis of this differential response is not known.
念珠菌生物膜的形成以及念珠菌属对抗真菌药物耐药性的增加，导致了义齿性口炎的高复发率。这种情况激发了人们对抗菌光动力疗法（aPDT）作为一种替代治疗方法的兴趣。我们研究了基于卟啉的光敏剂TMP - 1363对白色念珠菌、光滑念珠菌、热带念珠菌和近平滑念珠菌生物膜的光活性，以及咪康唑与aPDT联合使用的效果。在聚甲基丙烯酸甲酯（PMMA）圆盘上培养的三株美国典型培养物保藏中心（ATCC）菌株和四株临床分离株的生物膜，先用咪康唑孵育，然后在37°C下用TMP - 1363处理30分钟。平板在距离平板10 cm处暴露于宽带可见光下30分钟（平板表面辐照度：32.5 mW/cm²）。通过XTT法测定生物膜的代谢活性。ATCC菌株和光滑念珠菌7531/06对TMP - aPDT不敏感，而其余三株临床分离株的代谢活性降至对照的64.2±5.5%。25μg/ml的咪康唑降低了除ATCC菌株白色念珠菌MYA274之外所有菌株的活力；然而，它与aPDT联合使用对该菌株有效，表明存在协同相互作用。咪康唑和aPDT对白色念珠菌MYA 2732、白色念珠菌6122/06的作用是相加的。对于热带念珠菌和近平滑念珠菌，联合治疗具有更高但并非完全相加的细胞毒性作用。咪康唑和TMP - aPDT联合使用在治疗多种念珠菌属和菌株的生物膜方面具有优势，但并非对所有菌株都有效。这种差异反应的分子基础尚不清楚。
