Respiratory deficiency enhances the sensitivity of the pathogenic fungus Candida to photodynamic treatment
Respiratory deficiency enhances the sensitivity of the pathogenic fungus Candida to photodynamic treatment
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DOI：
10.1111/j.1751-1097.2007.00280.x
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发表时间：
2008-09-01
影响因子：
3.3
通讯作者：
Haidaris, Constantine G.
中科院分区：
文献类型：
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作者：
Chabrier-Rosello, Yeissa;Foster, Thomas H.;Haidaris, Constantine G.
由致病真菌念珠菌引起的粘液菌感染是一个重要的感染性疾病问题，并且由于对常规抗真菌剂的高频率耐药性而通常难以根除。光动力治疗（PDT）提供了一种有吸引力的治疗选择。以往的研究表明，丝状和生物膜的白色念珠菌是敏感的PDT使用Photofrin作为光敏剂。然而，早期稳定期酵母形式的C。白色念珠菌和光滑念珠菌没有受到治疗的不利影响。我们报道了阳离子卟啉光敏剂meso-四（N-甲基-4-吡啶基）卟啉四甲苯磺酸盐（TMP-1363）在光动力学疗法中对酵母菌型C.白色念珠菌和C.光滑的呼吸缺陷型（RD）C.白色念珠菌和念珠菌。光果葡菌显示多效性抗性模式，包括对唑类抗真菌剂家族成员、唾液抗微生物肽组蛋白和其他类型的毒性应激的抗性。与此相反，这两个C.白色念珠菌和念珠菌。glabrata对PDT的敏感性显著高于亲本菌株。这些数据表明，完整的线粒体功能可以提供一个基础水平的抗氧化防御PDT诱导的光毒性念珠菌，并揭示了抗氧化应激的途径，可以潜在地有针对性地增加PDT对这种致病性真菌的疗效。
Mucosal infections caused by the pathogenic fungus Candida are a significant infectious disease problem and are often difficult to eradicate because of the high frequency of resistance to conventional antifungal agents. Photodynamic treatment (PDT) offers an attractive therapeutic alternative. Previous studies demonstrated that filamentous forms and biofilms of Candida albicans were sensitive to PDT using Photofrin as a photosensitizer. However, early stationary phase yeast forms of C. albicans and Candida glabrata were not adversely affected by treatment. We report that the cationic porphyrin photosensitizer meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP-1363) is effective in PDT against yeast forms of C. albicans and C. glabrata. Respiratory-deficient (RD) strains of C. albicans and C. glabrata display a pleiotropic resistance pattern, including resistance to members of the azole family of antifungals, the salivary antimicrobial peptides histatins and other types of toxic stresses. In contrast to this pattern, RD mutants of both C. albicans and C. glabrata were significantly more sensitive to PDT compared to parental strains. These data suggest that intact mitochondrial function may provide a basal level of anti-oxidant defense against PDT-induced phototoxicity in Candida, and reveals pathways of resistance to oxidative stress that can potentially be targeted to increase the efficacy of PDT against this pathogenic fungus.