Cdc42p controls yeast-cell shape and virulence of Paracoccidioides brasiliensis

被引:53
作者
Almeida, A. J. [1 ]
Cunha, C. [1 ]
Carmona, J. A. [1 ]
Sampaio-Marques, B. [1 ]
Carvalho, A. [1 ]
Malavazi, I. [2 ]
Steensma, H. Y. [3 ]
Johnson, D. I. [4 ]
Leao, C. [1 ]
Logarinho, E. [1 ]
Goldman, G. H. [2 ]
Castro, A. G. [1 ]
Ludovico, P. [1 ]
Rodrigues, F. [1 ]
机构
[1] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Hlth Sci, P-4710057 Braga, Portugal
[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo, Brazil
[3] Leiden Univ, Inst Biol, Leiden, Netherlands
[4] Univ Vermont, Dept Microbiol & Mol Genet, Burlington, VT 05405 USA
关键词
Paracoccidioides brasiliensis; Dimorphic pathogenic fungus; Cdc42; Multiple budding; SACCHAROMYCES-CEREVISIAE; CANDIDA-ALBICANS; POLARIZED GROWTH; HYPHAL GROWTH; AGROBACTERIUM-TUMEFACIENS; CLAVICEPS-PURPUREA; GTPASE; HOMOLOG; CYCLE; PATHOGENICITY;
D O I
10.1016/j.fgb.2009.08.004
中图分类号
Q3 [遗传学];
学科分类号
071007 [遗传学];
摘要
Paracoccidioides brasiliensis is characterized by a multiple budding phenotype and a polymorphic cell growth, leading to the formation of cells with extreme variations in shape and size. Since Cdc42 is a pivotal molecule in establishing and maintaining polarized growth for diverse cell types, as well as during pathogenesis of certain fungi, we evaluated its role during cell growth and virulence of the yeast-form of P. brasiliensis. We used antisense technology to knock-down PbCDC42's expression in P. brasiliensis yeast cells, promoting a decrease in cell size and more homogenous cell growth, altering the typical polymorphism of wild-type cells. Reduced expression levels also lead to increased phagocytosis and decreased virulence in a mouse model of infection. We provide genetic evidences underlying Pbcdc42p as an important protein during host-pathogen interaction and the relevance of the polymorphic nature and cell size in the pathogenesis of P. brasiliensis. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:919 / 926
页数:8
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