Candida albicans septin mutants are defective for invasive growth and virulence

被引:77
作者
Warenda, AJ
Kauffman, S
Sherrill, TP
Becker, JA
Konopka, JB [1 ]
机构
[1] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA
[2] Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA
关键词
D O I
10.1128/IAI.71.7.4045-4051.2003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Hyphal growth of Candida albicans is implicated as an important virulence factor for this opportunistic human pathogen. Septin proteins, a family of cytoskeletal elements that regulate membrane events and are important for proper morphogenesis of C. albicans, were examined for their role in tissue invasion and virulence in the mouse model of systemic infection. In vitro, septin mutants are only mildly defective for hyphal growth in liquid culture but display pronounced defects for invasive growth into agar. In vivo, the septin mutants were found to exhibit attenuated virulence. However, mice infected with the mutants displayed high fungal burdens in their kidneys without obvious symptoms of disease. Histological examination of infected kidneys revealed defects in organ invasion for the cdc10Delta and cdc11Delta deletion mutants, which displayed both reduced tissue penetration and noninvasive fungal masses. Thus, the septin proteins are necessary for invasive growth, which appears to be more important to the successful pathogenesis of C. albicans than hyphal growth alone.
引用
收藏
页码:4045 / 4051
页数:7
相关论文
共 59 条
[21]   CELLULAR MORPHOGENESIS IN THE SACCHAROMYCES-CEREVISIAE CELL-CYCLE - LOCALIZATION OF THE CDC11 GENE-PRODUCT AND THE TIMING OF EVENTS AT THE BUDDING SITE [J].
FORD, SK ;
PRINGLE, JR .
DEVELOPMENTAL GENETICS, 1991, 12 (04) :281-292
[22]   Polymerization of purified yeast septins: Evidence that organized filament arrays may not be required for septin function [J].
Frazier, JA ;
Wong, ML ;
Longtine, MS ;
Pringle, JR ;
Mann, M ;
Mitchison, TJ ;
Field, C .
JOURNAL OF CELL BIOLOGY, 1998, 143 (03) :737-749
[23]   Linkage of adhesion, filamentous growth, and virulence in Candida albicans to a single gene, INT1 [J].
Gale, CA ;
Bendel, CM ;
McClellan, M ;
Hauser, M ;
Becker, JM ;
Berman, J ;
Hostetter, MK .
SCIENCE, 1998, 279 (5355) :1355-1358
[24]   Functional analysis of the interaction between Afr1p and the Cdc12p septin, two proteins involved in pheromone-induced morphogenesis [J].
Giot, L ;
Konopka, JB .
MOLECULAR BIOLOGY OF THE CELL, 1997, 8 (06) :987-998
[25]   The septin cortex at the yeast mother-bud neck [J].
Gladfelter, AS ;
Pringle, JR ;
Lew, DJ .
CURRENT OPINION IN MICROBIOLOGY, 2001, 4 (06) :681-689
[26]  
Gow Neil A. R., 1997, Current Topics in Medical Mycology, V8, P43
[27]   IMMUNOFLUORESCENCE LOCALIZATION OF THE SACCHAROMYCES-CEREVISIAE CDC12 GENE-PRODUCT TO THE VICINITY OF THE 10-NM FILAMENTS IN THE MOTHER-BUD NECK [J].
HAARER, BK ;
PRINGLE, JR .
MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (10) :3678-3687
[29]   Subunit composition, protein interactions, and structures of the mammalian brain sec6/8 complex and septin filaments [J].
Hsu, SC ;
Hazuka, CD ;
Roth, R ;
Foletti, DL ;
Heuser, J ;
Scheller, RH .
NEURON, 1998, 20 (06) :1111-1122
[30]   Ash1 protein, an asymmetrically localized transcriptional regulator, controls filamentous growth and virulence of Candida albicans [J].
Inglis, DO ;
Johnson, AD .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (24) :8669-8680