A Saccharomyces cerevisiae mutant with increased virulence

被引:80
作者
Wheeler, RT
Kupiec, M
Magnelli, P
Abeijon, C
Fink, GR [1 ]
机构
[1] MIT, Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02139 USA
[2] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel
[3] Boston Univ, Goldman Sch Dent Med, Dept Mol & Cell Biol, Boston, MA 02118 USA
关键词
D O I
10.1073/pnas.0437995100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Saccharomyces cerevisiae, bakers' yeast, is not a pathogen in healthy individuals, but is increasingly isolated from immunocompromised patients. The more frequent isolation of S. cerevisiae clinically raises a number of questions concerning the origin, survival, and virulence of this organism in human hosts. Here we compare the virulence of a human isolate, a strain isolated from decaying fruit, and a common laboratory strain in a mouse infection model. We find that the plant isolate is lethal in mice,whereas the laboratory strain is avirulent. A knockout of the SSD1 gene, which alters the composition and cell wall architecture of the yeast cell surface, causes both the clinical and plant isolates to be more virulent in the mouse model of infection. The hypervirulent ssd1Delta/ssd1Delta yeast strain is a more potent elicitor of proinflammatory cytokines from macrophages in vitro. Our data suggest that the increased virulence of the mutant strains is a consequence of unique surface characteristics that overstimulate the proinflammatory response.
引用
收藏
页码:2766 / 2770
页数:5
相关论文
共 30 条
[1]  
[Anonymous], 1991, Methods Enzymol, V194, P1
[2]   Septic shock [J].
Astiz, ME ;
Rackow, EC .
LANCET, 1998, 351 (9114) :1501-1505
[3]  
Brachmann CB, 1998, YEAST, V14, P115
[4]   Dectin-1 is a major β-glucan receptor on macrophages [J].
Brown, GD ;
Taylor, PR ;
Reid, DM ;
Willment, JA ;
Williams, DL ;
Martinez-Pomares, L ;
Wong, SYC ;
Gordon, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (03) :407-412
[5]   PATHOGENICITY OF SACCHAROMYCES-CEREVISIAE IN COMPLEMENT FACTOR-5 DEFICIENT MICE [J].
BYRON, JK ;
CLEMONS, KV ;
MCCUSKER, JH ;
DAVIS, RW ;
STEVENS, DA .
INFECTION AND IMMUNITY, 1995, 63 (02) :478-485
[6]   The serum mannose-binding protein and the macrophage mannose receptor are pattern recognition molecules that link innate and adaptive immunity [J].
Fraser, IP ;
Koziel, H ;
Ezekowitz, RAB .
SEMINARS IN IMMUNOLOGY, 1998, 10 (05) :363-372
[7]  
Goldstein AL, 2001, GENETICS, V159, P499
[8]  
Goldstein AL, 1999, YEAST, V15, P1541, DOI 10.1002/(SICI)1097-0061(199910)15:14<1541::AID-YEA476>3.0.CO
[9]  
2-K
[10]  
Haworth R, 1998, METHOD MICROBIOL, V25, P287