Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence

被引:236
作者
Hube, B
Sanglard, D
Odds, FC
Hess, D
Monod, M
Schafer, W
Brown, AJP
Gow, NAR
机构
[1] UNIV ABERDEEN, INST MED SCI, DEPT MOL & CELL BIOL, ABERDEEN AB25 2ZD, SCOTLAND
[2] CHU VAUDOIS, INST MICROBIOL, CH-1011 LAUSANNE, SWITZERLAND
[3] JANSSEN RES FDN, B-2340 BEERSE, BELGIUM
基金
英国惠康基金;
关键词
AUXOTROPHIC MUTANTS; EXPERIMENTAL INFECTIONS; ASPERGILLUS-FUMIGATUS; DEFICIENT MUTANT; ACID PROTEINASE; PATHOGENICITY; PROTEASE; TARGETS; YEAST; EXPRESSION;
D O I
10.1128/IAI.65.9.3529-3538.1997
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Secreted aspartyl proteinases (Saps), encoded by a gene family with at least nine members (SAP1 to SAP9), are one of the most discussed virulence factors produced by the human pathogen Candida albicans. In order to study the role of each Sap isoenzyme in pathogenicity, we have constructed strains which harbor mutations at selected SAP genes. SAP1, SAP2, and SAP3, which are regulated differentially in vitro, were mutated by targeted gene disruption. The growth rates of all homozygous null mutants were similar to those of the isogenic wild-type parental strain (SC5314) in complex and defined media. In medium with protein as the sole source of nitrogen, sap1 and sap3 mutants grew with reduced growth rates but reached optical densities similar: to those measured for SC5314. In contrast, sap2 null mutants tended to clump, grew poorly in this medium, and produced the lowest proteolytic activity. Addition of ammonium ions reversed such growth defects. These results support the view that Sap2 is the dominant isoenzyme. When sap1, sap2, and sap3 mutants were injected intravenously in guinea pigs and mice, the animals had increased survival rates compared to those of control animals infected with SC5314. However, reduction of proteolytic activity in vitro did not correlate directly with the extent of attenuation of virulence observed for all Sap-deficient mutants. These data suggest that SAP1, SAP2, and SAP3 all contribute to the overall virulence of C. albicans and presumably all play important roles during disseminated infections.
引用
收藏
页码:3529 / 3538
页数:10
相关论文
共 66 条
[1]   ATOPIC ASTHMA CAUSED BY CANDIDA-ALBICANS ACID PROTEASE - CASE-REPORTS [J].
AKIYAMA, K ;
SHIDA, T ;
YASUEDA, H ;
MITA, H ;
YAMAMOTO, T ;
YAMAGUCHI, H .
ALLERGY, 1994, 49 (09) :778-781
[2]  
Bodey GP., 1993, CANDIDIASIS PATHOGEN
[3]   A POSITIVE SELECTION FOR MUTANTS LACKING OROTIDINE-5'-PHOSPHATE DECARBOXYLASE ACTIVITY IN YEAST - 5-FLUORO-OROTIC ACID RESISTANCE [J].
BOEKE, JD ;
LACROUTE, F ;
FINK, GR .
MOLECULAR & GENERAL GENETICS, 1984, 197 (02) :345-346
[4]   EXPRESSION OF EXTRACELLULAR ACID PROTEINASE BY PROTEOLYTIC CANDIDA SPP DURING EXPERIMENTAL-INFECTION OF ORAL-MUCOSA [J].
BORG, M ;
RUCHEL, R .
INFECTION AND IMMUNITY, 1988, 56 (03) :626-631
[5]   EVIDENCE FOR A CORRELATION BETWEEN PROTEINASE SECRETION AND VULVO-VAGINAL CANDIDOSIS [J].
CASSONE, A ;
DEBERNARDIS, F ;
MONDELLO, F ;
CEDDIA, T ;
AGATENSI, L .
JOURNAL OF INFECTIOUS DISEASES, 1987, 156 (05) :777-783
[6]   Evidence for degradation of gastrointestinal mucin by Candida albicans secretory aspartyl proteinase [J].
Colina, AR ;
Aumont, F ;
Deslauriers, N ;
Belhumeur, P ;
deRepentigny, L .
INFECTION AND IMMUNITY, 1996, 64 (11) :4514-4519
[7]   PUTATIVE VIRULENCE FACTORS OF CANDIDA-ALBICANS [J].
CUTLER, JE .
ANNUAL REVIEW OF MICROBIOLOGY, 1991, 45 :187-218
[8]  
DEBERNARDIS F, 1990, J INFECT DIS, V161, P1276, DOI 10.1093/infdis/161.6.1276
[9]   Elevated aspartic proteinase secretion and experimental pathogenicity of Candida albicans isolates from oral cavities of subjects infected with human immunodeficiency virus [J].
DeBernardis, F ;
Chiani, P ;
Ciccozzi, M ;
Pellegrini, G ;
Ceddia, T ;
DOffizzi, G ;
Quinti, I ;
Sullivan, PA ;
Cassone, A .
INFECTION AND IMMUNITY, 1996, 64 (02) :466-471
[10]   CHARACTERIZATION OF CANDIDA-ALBICANS EPIDERMOLYTIC PROTEASES AND THEIR ROLE IN YEAST-CELL ADHERENCE TO KERATINOCYTES [J].
ELMAGHRABI, EA ;
DIXON, DM ;
BURNETT, JW .
CLINICAL AND EXPERIMENTAL DERMATOLOGY, 1990, 15 (03) :183-191