Transcriptome analysis of Paracoccidioides brasiliensis cells undergoing mycelium-to-yeast transition

被引:93
作者
Nunes, LR
de Oliveira, RC
Leite, DB
da Silva, VS
Marques, ED
Ferreira, MED
Ribeiro, DCD
Bernardes, LAD
Goldman, MHS
Puccia, R
Travassos, LR
Batista, WL
Nóbrega, MP
Nobrega, FG
Yang, DY
Pereira, CAD
Goldman, GH
机构
[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Ciencias Farmaceut, BR-14040903 Ribeirao Preto, SP, Brazil
[2] Univ Mogi Das Cruzes, Nucleo Integrado Biotecnol, Mogi Das Cruzes, Brazil
[3] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Pret, Sao Paulo, Brazil
[4] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo, Brazil
[5] Univ Vale Paraiba, BR-12244000 Sao Paulo, Brazil
[6] Univ Sao Paulo, Inst Matemat & Estatist, Sao Paulo, Brazil
[7] Tunghai Univ, Dept Chem, Taichung 40704, Taiwan
关键词
D O I
10.1128/EC.4.12.2115-2128.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Paracoccidioides brasiliensis is a thermodimorphic fungus associated with paracoccidioidomycosis (PCM), a systemic mycosis prevalent in South America. In humans, infection starts by inhalation of fungal propagules, which reach the pulmonary epithelium and transform into the yeast parasitic form. Thus, the mycelium-to-yeast transition is of particular interest because conversion to yeast is essential for infection. We have used a P. brasiliensis biochip carrying sequences of 4,692 genes from this fungus to monitor gene expression at several time points of the mycelium-to-yeast morphological shift (from 5 to 120 h). The results revealed a total of 2,583 genes that displayed statistically significant modulation in at least one experimental time point. Among the identified gene homologues, some encoded enzymes involved in amino acid catabolism, signal transduction, protein synthesis, cell wall metabolism, genome structure, oxidative stress response, growth control, and development. The expression pattern of 20 genes was independently verified by real-time reverse transcription-PCR, revealing a high degree of correlation between the data obtained with the two methodologies. One gene, encoding 4-hydroxyl-phenyl pyruvate dioxygenase (4-HPPD), was highly overexpressed during the mycelium-to-yeast differentiation, and the use of NTBC [2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione], a specific inhibitor of 4-HPPD activity, as well as that of NTBC derivatives, was able to inhibit growth and differentiation of the pathogenic yeast phase of the fungus in vitro. These data set the stage for further studies involving NTBC and its derivatives as new chemotherapeutic agents against PCM and confirm the potential of array-based approaches to identify new targets for the development of alternative treatments against pathogenic microorganisms.
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页码:2115 / 2128
页数:14
相关论文
共 57 条
  • [1] Characterization, localization and functional analysis of Gpr1p, a protein affecting sensitivity to acetic acid in the yeast Yarrowia lipolytica
    Augstein, A
    Barth, K
    Gentsch, M
    Kohlwein, SD
    Barth, G
    [J]. MICROBIOLOGY-SGM, 2003, 149 : 589 - 600
  • [2] Use of a histone H4 promoter to drive the expression of homologous and heterologous proteins by Penicillium funiculosum
    Belshaw, NJ
    Haigh, NP
    Fish, NM
    Archer, DB
    Alcocer, MJC
    [J]. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, 2002, 60 (04) : 455 - 460
  • [3] The pathobiology of Paracoccidioides brasiliensis
    Borges-Walmsley, MI
    Chen, DL
    Shu, XH
    Walmsley, AR
    [J]. TRENDS IN MICROBIOLOGY, 2002, 10 (02) : 80 - 87
  • [4] BOWTELL D, 2003, DNA MICROARRAYS MOL, P214
  • [5] Structure of the ferrous form of (4-hydroxyphenyl)pyruvate dioxygenase from Streptomyces avermitilis in complex with the therapeutic herbicide, NTBC
    Brownlee, JM
    Johnson-Winters, K
    Harrison, DHT
    Moran, GR
    [J]. BIOCHEMISTRY, 2004, 43 (21) : 6370 - 6377
  • [6] Virulence of Paracoccidioides brasiliensis and gp43 expression in isolates bearing known PbGP43 genotype
    Carvalho, KC
    Ganiko, L
    Batista, WL
    Morais, FV
    Marques, ER
    Goldman, GH
    Franco, ME
    Puccia, R
    [J]. MICROBES AND INFECTION, 2005, 7 (01) : 55 - 65
  • [7] Identification, N-terminal region sequencing and similarity analysis of differentially expressed proteins in Paracoccidioides brasiliensis
    Cunha, AF
    Sousa, MV
    Silva, SP
    Jesuíno, RSA
    Soares, CMA
    Felipe, MSS
    [J]. MEDICAL MYCOLOGY, 1999, 37 (02) : 115 - 121
  • [8] The highly expressed yeast gene pby20 from Paracoccidioides brasiliensis encodes a flavodoxin-like protein
    Daher, BS
    Venancio, EJ
    de Freitas, SM
    Báo, SN
    Vianney, PVR
    Andrade, RV
    Dantas, AS
    Soares, CMA
    Silva-Pereira, I
    Felipe, MSS
    [J]. FUNGAL GENETICS AND BIOLOGY, 2005, 42 (05) : 434 - 443
  • [9] Functional and genetic characterization of calmodulin from the dimorphic and pathogenic fungus Paracoccidioides brasiliensis
    de Carvalho, MJA
    Jesuino, RSA
    Daher, BS
    Silva-Pereira, I
    de Freitas, SM
    Soares, CMA
    Felipe, MSS
    [J]. FUNGAL GENETICS AND BIOLOGY, 2003, 39 (03) : 204 - 210
  • [10] Enzymes that counteract nitrosative stress promote fungal virulence
    de Jesús-Berríos, M
    Liu, LM
    Nussbaum, JC
    Cox, GM
    Stamler, JS
    Heitman, J
    [J]. CURRENT BIOLOGY, 2003, 13 (22) : 1963 - 1968