The Candida albicans Ddr48 protein is essential for filamentation, stress response, and confers partial antifungal drug resistance

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dc.contributor.author Khalaf, Roy A.
dc.contributor.author Hayek, Peter
dc.contributor.author Sadek, Helen
dc.contributor.author Beyrouthy, Berna
dc.contributor.author Dib, Leila
dc.date.accessioned 2016-03-21T09:03:53Z
dc.date.available 2016-03-21T09:03:53Z
dc.date.copyright 2008
dc.date.issued 2016-03-21
dc.identifier.issn 1234-1010 en_US
dc.identifier.uri http://hdl.handle.net/10725/3370
dc.description.abstract Background: Candida albicans is a dimorphic pathogenic fungus that causes mucosal and systemic infections. C. albicans pathogenicity is attributed to its ability to exist in different morphologic states and to respond to stress by up regulating several key genes. DDR48 is a stress-associated gene involved in DNA repair and in response to antifungal drug exposure. Malarial/Methods: One allele of DDR48was knocked out by homologous recombination that inserted a marker cassette in its position. Furthermore, reintroducing DDR48 on a plasmid created a revertant strain. Strains were grown on filamentation inducing and noninducing media, subjected to an oxidative stress challenge, injected into mice to assess virulence, and assayed for antifungal susceptibility by the E-test method. Results: DDR48 was found to be haploid insufficient and possibly essential, since only a heterozygote, but not a homozygous, null mutant was generated. The mutant was filamentation defective on all hyphal media tested including serum and corn meal agar. Discrepancies in drug resistance profiles also were present: Compared with the parental strain, DDR48/ddr48 heterozygote strain was susceptible in a dose-dependent manner to itraconazole and fluconazole and susceptible to ketoconazole. The mutant also appeared to be hypersensitive to a potentially lethal hydrogen peroxide challenge. However, no reduction in virulence of the mutant was observed. Conclusions: The present findings provide evidence that DDR48 is essential for filamentation, stress response, and possibly viability of C. albicans, making it a prime target for antifungal drug design. en_US
dc.language.iso en en_US
dc.title The Candida albicans Ddr48 protein is essential for filamentation, stress response, and confers partial antifungal drug resistance en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 200300427 en_US
dc.author.woa N/A en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Medical science monitor en_US
dc.journal.volume 14 en_US
dc.journal.issue 6 en_US
dc.keywords Candida albicans en_US
dc.keywords DDR48 en_US
dc.keywords Filamentation en_US
dc.keywords Virulence en_US
dc.keywords Drug susceptibility en_US
dc.keywords Stress response en_US
dc.author.email roy.khalaf@lau.edu.lb
dc.identifier.url http://www.medscimonit.com/abstract/index/idArt/859029/act/3

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