Effect of virulence factors on the photodynamic inactivation of Cryptococcus neoformans.

Effect of virulence factors on the photodynamic inactivation of Cryptococcus neoformans.
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DOI:
10.1371/journal.pone.0054387
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Hamblin MR
Hamblin MR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Prates RA;Fuchs BB;Mizuno K;Naqvi Q;Kato IT;Ribeiro MS;Mylonakis E;Tegos GP;Hamblin MR

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寄生性真菌病原体可引起一系列浅表感染或严重的侵袭性感染,尤其是在免疫功能低下的患者中。新型隐球菌是引起HIV/AIDS患者隐球菌病的病原体,但由于相对缺乏有效的抗真菌剂,治疗受到限制。光动力失活(PDI)使用称为光敏剂的无毒染料和无害可见光的组合,其产生单线态氧和其他活性氧物质,从而产生细胞失活和死亡。我们报告了使用五种结构无关的光敏剂(亚甲蓝,玫瑰红,硒衍生物的尼罗蓝染料,阳离子富勒烯和共轭聚-L-赖氨酸和二氢卟酚(e6))结合适当波长的光,以pH 2C。新人类缺乏荚膜和漆酶的突变体,以及有利于黑色素产生的培养条件被用来探索PDI的机制和毒力因子的影响。细胞壁、漆酶和黑色素的存在倾向于防止PDI,但选择适当的光敏剂和剂量学能够克服这种阻力。
Opportunistic fungal pathogens may cause an array of superficial infections or serious invasive infections, especially in immunocompromised patients. Cryptococcus neoformans is a pathogen causing cryptococcosis in HIV/AIDS patients, but treatment is limited due to the relative lack of potent antifungal agents. Photodynamic inactivation (PDI) uses the combination of non-toxic dyes called photosensitizers and harmless visible light, which produces singlet oxygen and other reactive oxygen species that produce cell inactivation and death. We report the use of five structurally unrelated photosensitizers (methylene blue, Rose Bengal, selenium derivative of a Nile blue dye, a cationic fullerene and a conjugate between poly-L-lysine and chlorin(e6)) combined with appropriate wavelengths of light to inactivate C. neoformans. Mutants lacking capsule and laccase, and culture conditions that favoured melanin production were used to probe the mechanisms of PDI and the effect of virulence factors. The presence of cell wall, laccase and melanin tended to protect against PDI, but the choice of the appropriate photosensitizers and dosimetry was able to overcome this resistance.
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