Document Detail


Development of oxidative stress tolerance resulted in reduced ability to undergo morphologic transitions and decreased pathogenicity in a t-butylhydroperoxide-tolerant mutant of Candida albicans.
MedLine Citation:
PMID:  17498215     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We tested the hypothesis that adaptation of Candida albicans to chronic oxidative stress inhibits the formation of hyphae and reduces pathogenicity. Candida albicans cells were exposed to increasing concentrations of t-butylhydroperoxide (tBOOH), a lipid peroxidation-accelerating agent, and mutants with heritable tBOOH tolerance were isolated. Hypha formation by the mutants was negligible on Spider agar, indicating that the development of oxidative stress tolerance prevented Candida cells from undergoing dimorphic switches. One of the mutants, C. albicans AF06, was five times less pathogenic in mice than its parental strain, due to its reduced germ tube-, pseudohypha- and hypha-forming capability, and decreased phospholipase secretion. An increased oxidative stress tolerance may therefore be disadvantageous when this pathogen leaves blood vessels and invades deep organs. The AF06 mutant was characterized by high intracellular concentrations of endogenous oxidants, reduced monounsaturated and polyunsaturated fatty acid contents, the continuous induction of the antioxidative defense system, decreased cytochrome c-dependent respiration, and increased alternative respiration. The mutation did not influence growth rate, cell size, cell surface, cellular ultrastructures, including mitochondria, or recognition by human polymorphonuclear leukocytes. The selection of oxidative stress-tolerant respiratory Candida mutants may also occur in vivo, when reduced respiration helps the fungus to cope with antimycotic agents.
Authors:
Andrea Fekete; Tamás Emri; Agnes Gyetvai; Zoltán Gazdag; Miklós Pesti; Zsuzsa Varga; József Balla; Csaba Cserháti; Levente Emody; Lajos Gergely; István Pócsi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-05-10
Journal Detail:
Title:  FEMS yeast research     Volume:  7     ISSN:  1567-1356     ISO Abbreviation:  FEMS Yeast Res.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-16     Completed Date:  2009-09-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101085384     Medline TA:  FEMS Yeast Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  834-47     Citation Subset:  IM    
Affiliation:
Department of Microbial Biotechnology and Cell Biology, Faculty of Science, University of Debrecen, Debrecen, Hungary.
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological / genetics,  physiology*
Animals
Antifungal Agents / pharmacology
Candida albicans / cytology,  drug effects,  genetics,  growth & development,  pathogenicity*,  physiology*
Cell Size
DNA, Fungal / chemistry
Gene Expression Regulation, Fungal
Humans
Hyphae / growth & development
Lipid Peroxidation / physiology
Mice
Mutation / genetics*
Oxidative Stress / drug effects,  physiology*
Virulence Factors / metabolism
tert-Butylhydroperoxide / pharmacology*
Chemical
Reg. No./Substance:
0/Antifungal Agents; 0/DNA, Fungal; 0/Virulence Factors; 75-91-2/tert-Butylhydroperoxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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