Reduced virulence of HWP1-deficient mutants of Candida albicans and their interactions with host cells

被引:98
|
作者
Tsuchimori, N
Sharkey, LL
Fonzi, WA
French, SW
Edwards, JE
Filler, SG
机构
[1] Univ Calif Los Angeles, Harbor Res & Educ Inst, Div Infect Dis, Torrance, CA 90502 USA
[2] Georgetown Univ, Med Ctr, Sch Med, Dept Microbiol & Immunol, Washington, DC 20007 USA
[3] Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90024 USA
[4] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA
关键词
D O I
10.1128/IAI.68.4.1997-2002.2000
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The Candida albicans gene HWP1 encodes a surface protein that is required for normal hyphal development in vitro. We used mutants lacking one or both alleles of HWP1 to investigate the role of this gene in virulence. Mice infected intravenously,vith the homozygous hwp1 null mutant, CAL3, survived a median of >14 days, whereas mice infected with a control strain containing two functional alleles of HWP1 survived only 3.5 days. After 1 day of infection, all strains produced similar levels of infection in the kidneys, spleen, and blood, However, after 2 and 3 days, there was a significant decrease in the number of organisms in the kidneys of the mice infected with CAL3. This finding suggests that the hwp1 homozygous null mutant is normal in its ability to initiate infection but deficient in its capacity to maintain infection. CAL3 also germinated minimally in the kidneys. The ability of the heterozygous null mutant to germinate and cause mortality in mice was intermediate to CAL3, suggesting a gene dosage effect. To investigate potential mechanisms for the diminished virulence of CAL3, we examined its interactions with endothelial cells and neutrophils in vitro. CAL3 caused less endothelial cell injury than the heterozygous hwp1 mutant. We conclude that the HWP1 gene product is important for both in vivo hyphal development and pathogenicity of C. albicans. Also, the ability to form filaments may be critical for candidal virulence by enabling the fungus to induce cellular injury and maintain a deep-seated infection.
引用
收藏
页码:1997 / 2002
页数:6
相关论文
共 50 条
  • [1] REDUCED VIRULENCE OF CANDIDA-ALBICANS PHR1 MUTANTS
    GHANNOUM, MA
    SPELLBERG, B
    SAPORITOIRWIN, SM
    FONZI, WA
    INFECTION AND IMMUNITY, 1995, 63 (11) : 4528 - 4530
  • [2] ATTENUATED VIRULENCE OF CHITIN-DEFICIENT MUTANTS OF CANDIDA-ALBICANS
    BULAWA, CE
    MILLER, DW
    HENRY, LK
    BECKER, JM
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (23) : 10570 - 10574
  • [3] VIRULENCE OF CANDIDA-ALBICANS MUTANTS
    POLAK, A
    MYCOSES, 1992, 35 (1-2) : 9 - 16
  • [4] Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence
    Maras, Bruno
    Maggiore, Anna
    Mignogna, Giuseppina
    D'Erme, Maria
    Angiolella, Letizia
    PLOS ONE, 2021, 16 (06):
  • [5] REDUCED VIRULENCE OF CANDIDA-ALBICANS MUTANTS AFFECTED IN MULTIDRUG-RESISTANCE
    BECKER, JM
    HENRY, LK
    JIANG, WD
    KOLTIN, Y
    INFECTION AND IMMUNITY, 1995, 63 (11) : 4515 - 4518
  • [6] Phenotypic Plasticity Regulates Candida albicans Interactions and Virulence in the Vertebrate Host
    Mallick, Emily M.
    Bergeron, Audrey C.
    Jones, Stephen K., Jr.
    Newman, Zachary R.
    Brothers, Kimberly M.
    Creton, Robbert
    Wheeler, Robert T.
    Bennett, Richard J.
    FRONTIERS IN MICROBIOLOGY, 2016, 7
  • [7] Interactions of Candida albicans with the host
    Hube, B.
    MEDICAL MYCOLOGY, 2018, 56 : S20 - S20
  • [8] Candida albicans HWP1 gene expression and host antibody responses in colonization and disease
    Naglik, Julian R.
    Fostira, Florentia
    Ruprai, Jasmeet
    Staab, Janet F.
    Challacombe, Stephen J.
    Sundstrom, Paula
    JOURNAL OF MEDICAL MICROBIOLOGY, 2006, 55 (10) : 1323 - 1327
  • [9] Candida albicans Adhesins Als1 and Hwp1 Modulate Interactions with Streptococcus mutans
    Martorano-Fernandes, Loyse
    Goodwine, James G. S.
    Ricomini-Filho, Antonio Pedro
    Nobile, Clarissa J. J.
    Del Bel Cury, Altair Antoninha
    MICROORGANISMS, 2023, 11 (06)
  • [10] Molecular mechanisms of virulence in fungus-host interactions for Aspergillus fumigatus and Candida albicans
    Muhlschlegal, F
    Fonzi, W
    Hoyer, L
    Payne, T
    Poulet, FM
    Clevenger, J
    Latge, JP
    Calera, J
    Beauvais, A
    Paris, S
    Monod, M
    Sturtevant, J
    Ghannoum, M
    Nozawa, Y
    Calderone, R
    MEDICAL MYCOLOGY, 1998, 36 : 238 - 248