Candida albicans Hyr1p Confers Resistance to Neutrophil Killing and Is a Potential Vaccine Target

被引：94

作者：

Luo, Guanpingsheng ^{[1
]}

Ibrahim, Ashraf S. ^{[1
,2
]}

Spellberg, Brad ^{[1
,2
]}

Nobile, Clarissa J. ^{[3
]}

Mitchell, Aaron P. ^{[4
]}

Fu, Yue ^{[1
,2
]}

机构：

[1] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Infect Dis, Torrance, CA 90502 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[3] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

[4] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 2010年 / 201卷 / 11期

关键词：

IMPROVES SURVIVAL; VIRULENCE; MICE; GENE; PATHOGENESIS; MACROPHAGES; MORPHOLOGY; INFECTION; GLABRATA; BLOOD;

D O I：

10.1086/652407

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Candida albicans is the most common cause of invasive fungal infections in humans. It is unclear how C. albicans escapes from phagocytic attack and survives in the hostile blood environment during life-threatening systemic infections. Using a conditional overexpression or suppression genetic strategy, we discovered that HYR1 gene reduced phagocytic killing activity of C. albicans in vitro and increased tissue fungal burden in vivo. Concordant with its positive regulation by the transcription factor Bcr1p, autonomous expression of HYR1 complemented the hypersusceptibility to phagocyte-mediated killing of a bcr1 null mutant of C. albicans in vitro. As for C. albicans, heterologous expression of HYR1 in Candida glabrata rendered the organism more resistant to neutrophil killing activity. Vaccination with a recombinant Hyr1p significantly protected mice against hematogenously disseminated candidiasis (p = .001). Finally, anti-rHyr1p polyclonal antibodies enhanced mouse neutrophil killing activity by directly neutralizing rHyr1p effects in vitro. Thus, Hyr1 is an important virulence factor for C. albicans, mediating resistance to phagocyte killing. Hyr1p is a promising target for vaccine or other immunological or small molecule intervention to improve the outcomes of disseminated candidiasis.

引用

页码：1718 / 1728

页数：11

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