Role of filamentation in Galleria mellonella killing by Candida albicans.
Role of filamentation in Galleria mellonella killing by Candida albicans.
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DOI：
10.1016/j.micinf.2010.03.001
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发表时间：
2010-06
影响因子：
5.8
通讯作者：
Mylonakis E
中科院分区：
文献类型：
--
作者：
Fuchs BB;Eby J;Nobile CJ;El Khoury JB;Mitchell AP;Mylonakis E
白色念珠菌是住院患者和免疫抑制患者发病的重要原因。白色念珠菌的毒力因子包括：丝状形成、蛋白酶、粘附蛋白和生物膜形成。这项工作的目的是使用大蜡螟作为模型来研究白色念珠菌丝状化在毒力中的作用。我们的研究重点是 BCR1、FLO8、KEM1、SUV3 和 TEC1 五个基因，这些基因已被证明在丝状形成中发挥作用。在哺乳动物感染中，丝对于生物膜的形成和避免与巨噬细胞的相互作用是必需的。在测试的五个突变菌株中，我们发现只有flo8/flo8突变菌株在大蜡螟内没有形成丝。该菌株还表现出对幼虫的毒力降低。另一种在大蜡螟模型中表现出致病性降低的菌株是 tec1/tec1，但相比之下，tec1/tec1 菌株保留了形成丝的能力。 flo8/flo8 突变体中 TEC1 的过度表达恢复了丝状形成，但没有恢复幼虫以及白色念珠菌感染的小鼠模型中的毒力。丝状表型不影响血细胞（大蜡螟的免疫细胞）与各种白色念珠菌突变株相关的能力。 tec1/tec1 突变体和 flo8/flo8 TDH3-TEC1 菌株形成毒力受损的丝状体的能力表明，仅丝状化不足以杀死大蜡螟，并表明其他毒力因子可能与调节丝状化的基因有关。
Candida albicans is an important cause of morbidity in hospitalized and immunosuppressed patients. Virulence factors of C. albicans include: filamentation, proteinases, adherence proteins and biofilm formation. The objective of this work was to use Galleria mellonella as a model to study the roles of C. albicans filamentation in virulence. We focused our study to five genes BCR1, FLO8, KEM1, SUV3 and TEC1 that have been shown to play a role in filamentation. Filaments are necessary for biofilm formation and evading interaction with macrophages in mammalian infections. Among the five mutant strain tested, we found that only the flo8/flo8 mutant strain did not form filaments within G. mellonella. This strain also exhibited reduced virulence in the larvae. Another strain that exhibited reduced pathogenicity in the G. mellonella model was tec1/tec1 but by contrast, the tec1/tec1 strain retained the ability to form filaments. Overexpression of TEC1 in the flo8/flo8 mutant restored filamentation but did not restore virulence in the larvae as well as in a mouse model of C. albicans infection. The filamentation phenotype did not affect the ability of hemocytes, the immune cells of G. mellonella, to associate with the various mutant strains of C. albicans. The capacities of the tec1/tec1 mutant and the flo8/flo8 TDH3-TEC1 strains to form filaments with impaired virulence suggest that filamentation alone is not sufficient to kill G. mellonella and suggest other virulence factors may be associated with genes that regulate filamentation.
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影响因子：
64.5
作者：
Lo, HJ;Kohler, JR;Fink, GR
通讯作者：
Fink, GR
影响因子：
6.7
作者：
Breger J;Fuchs BB;Aperis G;Moy TI;Ausubel FM;Mylonakis E
通讯作者：
Mylonakis E
影响因子：
9.2
作者：
Nobile, CJ;Mitchell, AP
通讯作者：
Mitchell, AP
影响因子：
3.1
作者：
Davis, D;Edwards, JE;Ibrahim, AS
通讯作者：
Ibrahim, AS
影响因子：
3.2
作者：
Wilson, RB;Davis, D;Mitchell, AP
通讯作者：
Mitchell, AP