Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate.

Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate.
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念珠菌对抗真菌性的敏感性和吞噬作用受到乙酸酯的调节。

DOI:
10.3389/fmicb.2015.00919
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发表时间:
2015
影响因子:
5.2
通讯作者:
Paiva S
Paiva S
中科院分区:
生物学2区
文献类型:
--
作者:
Mota S;Alves R;Carneiro C;Silva S;Brown AJ;Istel F;Kuchler K;Sampaio P;Casal M;Henriques M;Paiva S

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光滑念珠菌被认为是人类的主要机会致病真菌。这种酵母菌引起感染的能力取决于在人类宿主环境中生长和同化可用碳源的能力。以往的研究表明,C。白色念珠菌在感染期间可遇到葡萄糖贫乏的微环境,并且使用替代的不可发酵碳源(例如羧酸)的能力有助于该真菌的毒力。对C. glabrata细胞在营养缺乏时也有类似的反应。在这项工作中,我们的目的是分析生物膜的形成,抗真菌药物的耐药性,和吞噬功能的C。glabrata细胞在乙酸作为替代碳源的存在下生长。C.与不含乙酸的培养基相比,在含乙酸的培养基中生长的光滑藻细胞对氟康唑更敏感,并且更好地被巨噬细胞吞噬和杀死。乙酸中的生长也影响了C. glabrata以形成生物膜。编码羧酸转运蛋白的基因ADY2a、ADY2b、FPS1、FPS2和ATO 3在C. glabrataestonic和生物膜细胞在乙酸的存在下。fps1和ady2a突变株的吞噬试验表明,FPS1和ADY2a在吞噬过程中的潜在作用。这些结果突出了与乙酸的存在相关的酸性pH小生境如何影响C.光滑念珠菌感染,特别是阴道念珠菌病。
Candida glabrata is considered a major opportunistic fungal pathogen of humans. The capacity of this yeast species to cause infections is dependent on the ability to grow within the human host environment and to assimilate the carbon sources available. Previous studies have suggested that C. albicans can encounter glucose-poor microenvironments during infection and that the ability to use alternative non-fermentable carbon sources, such as carboxylic acids, contributes to the virulence of this fungus. Transcriptional studies on C. glabrata cells identified a similar response, upon nutrient deprivation. In this work, we aimed at analyzing biofilm formation, antifungal drug resistance, and phagocytosis of C. glabrata cells grown in the presence of acetic acid as an alternative carbon source. C. glabrata planktonic cells grown in media containing acetic acid were more susceptible to fluconazole and were better phagocytosed and killed by macrophages than when compared to media lacking acetic acid. Growth in acetic acid also affected the ability of C. glabrata to form biofilms. The genes ADY2a, ADY2b, FPS1, FPS2, and ATO3, encoding putative carboxylate transporters, were upregulated in C. glabrata planktonic and biofilm cells in the presence of acetic acid. Phagocytosis assays with fps1 and ady2a mutant strains suggested a potential role of FPS1 and ADY2a in the phagocytosis process. These results highlight how acidic pH niches, associated with the presence of acetic acid, can impact in the treatment of C. glabrata infections, in particular in vaginal candidiasis.