Division of Infectious Disease, Massachusetts General Hospital, Boston, MA 02114, USA.
Microbes Infect. 2010 Jun;12(6):488-96. doi: 10.1016/j.micinf.2010.03.001. Epub 2010 Mar 9.
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.
白色念珠菌是住院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：菌丝形成、蛋白酶、黏附蛋白和生物膜形成。本工作的目的是使用大蜡螟作为模型来研究白色念珠菌菌丝形成在毒力中的作用。我们将研究重点放在已证明在菌丝形成中起作用的五个基因 BCR1、FLO8、KEM1、SUV3 和 TEC1 上。菌丝对于生物膜形成和逃避哺乳动物感染中与巨噬细胞的相互作用是必要的。在测试的五个突变菌株中，我们发现只有 flo8/flo8 突变菌株在大蜡螟体内不能形成菌丝。该菌株在幼虫中的毒力也降低了。另一个在大蜡螟模型中表现出降低致病性的菌株是 tec1/tec1，但与此相反，tec1/tec1 菌株仍然能够形成菌丝。在 flo8/flo8 突变体中过表达 TEC1 恢复了菌丝形成，但在幼虫和白色念珠菌感染的小鼠模型中并没有恢复毒力。菌丝形成表型并不影响血细胞（大蜡螟的免疫细胞）与白色念珠菌各种突变菌株结合的能力。tec1/tec1 突变体和 flo8/flo8 TDH3-TEC1 菌株形成菌丝的能力受损，但毒力降低，这表明单独的菌丝形成不足以杀死大蜡螟，并且可能还有其他毒力因子与调节菌丝形成的基因有关。
