Elucidation of potentially virulent factors of Candida albicans during serum adaptation by using quantitative time-course proteomics

被引:15
作者
Aoki, Wataru [1 ,2 ]
Tatsukami, Yohei [2 ]
Kitahara, Nao [2 ]
Matsui, Kazuma [2 ]
Morisaka, Hironobu [2 ]
Kuroda, Kouichi [2 ]
Ueda, Mitsuyoshi [2 ]
机构
[1] Japan Soc Promot Sci, Sakyo Ku, Kyoto 6068502, Japan
[2] Kyoto Univ, Grad Sch Agr, Div Appl Life Sci, Sakyo Ku, Kyoto 6068502, Japan
基金
日本学术振兴会;
关键词
Candida albicans; Quantitative proteome; Serum; Stress-tolerance; AMINO-ACID STARVATION; STRESS RESPONSES; SURFACE-PROTEINS; LEUCINE ZIPPER; GENE FAMILY; IDENTIFICATION; MORPHOGENESIS; ANNOTATION; RESISTANCE; ENZYMES;
D O I
10.1016/j.jprot.2013.07.031
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Candida albicans is an opportunistic pathogen that causes fatal disease if the host immunity is compromised. The mortality rate of systemic candidiasis is very high; hence, there is a ceaseless demand for novel pharmaceuticals. In this study, quantitative time-course proteomics of C. albicans during adaptation to fetal bovine serum (PBS) is described. Survival in blood is essential for virulence of C. albicans, and a detailed analysis is required. We cultivated C. albicans in FBS for 0-180 min, and determined quantitative time-course variations of 1024 proteins in the cultured cells by using a LC-MS/MS system with a long monolithic silica capillary column. Clustering analysis identified PBS-induced proteins associated with detoxification of oxidative species, high-affinity glucose transport, citrate cycle, oxidative phosphorylation, and iron acquisition. Furthermore, we identified possible virulence factors such as orf19.4914.1 (named Blood-induced peptide 1, Blp1). Heterologous expression of BLP1 in Saccharomyces cerevisiae shortened the lag phase and resulted in a pleiotropic stress-tolerance phenotype, indicating a possible role for quick adaptation to a stressful environment. While further experiments are necessary to prove virulence of the identified factors, systematic identification of candidate virulence proteins in this study will lead to profound understanding of virulence of C. albicans. Biological significance This paper describes time-course proteomics of C. albicans during adaptation to serum, which is an essential process for fatal systemic candidiasis. Using a LC-MS/MS system with a monolithic silica capillary column, we have successfully characterized time-course variations of 1024 proteins. Among them, orf19.4914.1 (Blp1) was identified as a novel pleiotropic stress-tolerance peptide, which could have an important role for virulence of C. albicans. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:417 / 429
页数:13
相关论文
共 62 条
[31]   Proteomic analysis of the oxidative stress responses in Candida albicans [J].
Kusch, Harald ;
Engelmann, Susanne ;
Albrecht, Dirk ;
Morschhaeuser, Joachim ;
Hecker, Michael .
PROTEOMICS, 2007, 7 (05) :686-697
[32]   Regulatory networks affected by iron availability in Candida albicans [J].
Lan, CY ;
Rodarte, G ;
Murillo, LA ;
Jones, T ;
Davis, RW ;
Dungan, J ;
Newport, G ;
Agabian, N .
MOLECULAR MICROBIOLOGY, 2004, 53 (05) :1451-1469
[33]   THE LEUCINE ZIPPER - A HYPOTHETICAL STRUCTURE COMMON TO A NEW CLASS OF DNA-BINDING PROTEINS [J].
LANDSCHULZ, WH ;
JOHNSON, PF ;
MCKNIGHT, SL .
SCIENCE, 1988, 240 (4860) :1759-1764
[34]   Candida albicans Hgt1p, a Multifunctional Evasion Molecule: Complement Inhibitor, CR3 Analogue, and Human Immunodeficiency Virus-Binding Molecule [J].
Lesiak-Markowicz, Iwona ;
Vogl, Georgia ;
Schwarzmueller, Tobias ;
Speth, Cornelia ;
Lass-Floerl, Cornelia ;
Dierich, Manfred P. ;
Kuchler, Karl ;
Wuerzner, Reinhard .
JOURNAL OF INFECTIOUS DISEASES, 2011, 204 (05) :802-809
[35]   Nonfilamentous C-albicans mutants are avirulent [J].
Lo, HJ ;
Kohler, JR ;
DiDomenico, B ;
Loebenberg, D ;
Cacciapuoti, A ;
Fink, GR .
CELL, 1997, 90 (05) :939-949
[36]   Identification of Candida albicans exposed surface proteins in vivo by a rapid proteomic approach [J].
Luisa Hernaez, Maria ;
Ximenez-Embun, Pilar ;
Martinez-Gomariz, Montserrat ;
Dolores Gutierrez-Blazquez, Maria ;
Nombela, Cesar ;
Gil, Concha .
JOURNAL OF PROTEOMICS, 2010, 73 (07) :1404-1409
[37]   Superoxide dismutases in Candida albicans:: Transcriptional regulation and functional characterization of the hyphal-induced SOD5 gene [J].
Martchenko, M ;
Alarco, AM ;
Harcus, D ;
Whiteway, M .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (02) :456-467
[38]   Proteomic analysis of cytoplasmic and surface proteins from yeast cells, hyphae, and biofilms of Candida albicans [J].
Martinez-Gomariz, Montserrat ;
Perumal, Palani ;
Mekala, Satish ;
Nombela, Cesar ;
Chaffin, W. LaJean ;
Gil, Concha .
PROTEOMICS, 2009, 9 (08) :2230-2252
[39]   Small but Crucial: The Novel Small Heat Shock Protein Hsp21 Mediates Stress Adaptation and Virulence in Candida albicans [J].
Mayer, Francois L. ;
Wilson, Duncan ;
Jacobsen, Ilse D. ;
Miramon, Pedro ;
Slesiona, Silvia ;
Bohovych, Iryna M. ;
Brown, Alistair J. P. ;
Hube, Bernhard .
PLOS ONE, 2012, 7 (06)
[40]   The PSIPRED protein structure prediction server [J].
McGuffin, LJ ;
Bryson, K ;
Jones, DT .
BIOINFORMATICS, 2000, 16 (04) :404-405