Pyrifenox, an ergosterol inhibitor, differentially affects Cryptococcus neoformans and Cryptococcus gattii.

Pyrifenox, an ergosterol inhibitor, differentially affects Cryptococcus neoformans and Cryptococcus gattii.
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Pyrifenox 是一种麦角甾醇抑制剂,对新型隐球菌和格特隐球菌有不同的影响。

DOI:
10.1093/mmy/myz132
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发表时间:
2020
期刊:
影响因子:
2.9
通讯作者:
Silva VKA
Silva VKA
中科院分区:
医学3区
文献类型:
--
作者:
Silva VKA

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隐球菌病是一种危及生命的真菌感染。新的治疗方法是必要的,以打击隐球菌病,因为目前可用的治疗方案是昂贵的,通常会导致有害的副作用。吡氟醚是一种抗真菌化合物,通过抑制麦角固醇的生物合成来影响植物病原体。本文研究了吡蚜醚对新生隐球菌和隐球菌生长、荚膜结构和主要荚膜成分葡糖醛木甘露聚糖(GXM)输出的影响。吡蚜酮抑制C. neoformans,但对C.加提。C. gattiito pyrifenox与外排泵基因,特别是AFR 1和AFR 2的表达相关,因为缺乏这些基因表达的突变细胞变得对pyrifenox敏感。隐球菌荚膜的印度墨水复染,免疫荧光和扫描电子显微镜分析表明,pyrifenox影响两个物种的荚膜尺寸。而C组GXM纤维较短,分布较均匀。neoformans,而inC.纤维的数量减少。Pyrifenox处理C. gattii发育出不寻常的长链不分裂的细胞。吡蚜酮处理后,GXM的分泌显着减少,在这两个物种。综上所述,吡蚜酮对C. neoformans和C.加提。此外,它强调了吡蚜酮作为GXM输出抑制剂在涉及致病性隐球菌的实验模型中的潜在作用。
Cryptococcosis is a life-threatening fungal infection. New therapeutic approaches are necessary to combat cryptococcosis, as the currently available therapeutic protocols are expensive and generally result in deleterious side effects. Pyrifenox is an antifungal compound that affects phytopathogens by inhibiting the biosynthesis of ergosterol. In this study, we investigated the effects of pyrifenox onCryptococcus neoformansandCryptococcus gattiigrowth, capsule architecture and export of the major capsule component, glucuroxylomannan (GXM). Pyrifenox inhibited the growth ofC. neoformans, but was significantly less effective againstC. gattii. The resistance ofC. gattiito pyrifenox was associated with the expression of efflux pump genes, particularlyAFR1andAFR2, since mutant cells lacking expression of these genes became sensitive to pyrifenox. Analysis of the cryptococcal capsule by India ink counterstaining, immunofluorescence, and scanning electron microscopy showed that pyrifenox affected capsular dimensions in both species. However, GXM fibers were shorter and uniformly distributed inC. neoformans, whereas inC. gattiithe number of fibers was reduced. Pyrifenox-treatedC. gattiideveloped unusually long chains of undivided cells. The secretion of GXM was markedly reduced in both species after treatment with pyrifenox. Altogether, the results indicated that pyrifenox differently affectsC. neoformansandC. gattii. In addition, it highlights a potential role for pyrifenox as an inhibitor of GXM export in experimental models involving pathogenic cryptococci.
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