Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

29 May 2008

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

Leila DibBCDF, Peter HayekBCF, Helen SadekC, Berna BeyrouthyCD, Roy A. KhalafACDEF

Med Sci Monit 2008; 14(6): BR113-121 :: ID: 859029

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.
Material and Method
One allele of DDR48 was 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.

Keywords: Oxidative Stress - drug effects, Microbial Sensitivity Tests, Mice, Mice, Inbred BALB C, Hyphae - growth & development, Heterozygote, Gene Deletion, Fungal Proteins - metabolism, Drug Resistance, Fungal - drug effects, Virulence, Phenotype, Culture Media, Candida albicans - pathogenicity, Antifungal Agents - pharmacology, Animals

0 Comments

Editorial

01 December 2021 : Editorial  

Editorial: SARS-CoV-2 Vaccine Responses and Breakthrough COVID-19

Dinah V. Parums
Scientific Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.935624

Med Sci Monit 2021; 27:e935624

SARS-CoV-2/COVID-19

03 December 2021 : Laboratory Research  

Influenza and Influenza-Like Respiratory Virus Infections in Children During the 2019/20 Influenza Season a...

Med Sci Monit In Press; DOI: 10.12659/MSM.934862  

08 November 2021 : Database Analysis  

Virtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Cor...

Med Sci Monit In Press; DOI: 10.12659/MSM.934102  

01 December 2021 : Editorial  

Editorial: SARS-CoV-2 Vaccine Responses and Breakthrough COVID-19

Med Sci Monit 2021; 27:e935624

In Press

06 Dec 2021 : Animal Research  

Astragalus Flavone Induces Proliferation and Differentiation of Neural Stem Cells in a Cerebral Infarction ...

Med Sci Monit In Press; DOI: 10.12659/MSM.933830  

06 Dec 2021 : Clinical Research  

Alteration of Serum Metabolites in Women of Reproductive Age with Chronic Constipation

Med Sci Monit In Press; DOI: 10.12659/MSM.934117  

06 Dec 2021 : Clinical Research  

Body Composition Changes and Related Factors in Patients with Ulcerative Colitis: A Retrospective Single-Ce...

Med Sci Monit In Press; DOI: 10.12659/MSM.933942  

03 Dec 2021 : Clinical Research  

A Retrospective Single-Center Study of 23 Patients to Compare Gait Before and After Total Hip Arthroplasty ...

Med Sci Monit In Press; DOI: 10.12659/MSM.934558  

Most Viewed Current Articles

20 Mar 2020 : Clinical Research  

Social Capital and Sleep Quality in Individuals Who Self-Isolated for 14 Days During the Coronavirus Diseas...

DOI :10.12659/MSM.923921

Med Sci Monit 2020; 26:e923921

15 Apr 2020 : Clinical Research  

Psychological Impact and Coping Strategies of Frontline Medical Staff in Hunan Between January and March 20...

DOI :10.12659/MSM.924171

Med Sci Monit 2020; 26:e924171

05 May 2020 : Review article  

An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development

DOI :10.12659/MSM.924700

Med Sci Monit 2020; 26:e924700

26 Apr 2020 : Clinical Research  

Comparison of Prevalence and Associated Factors of Anxiety and Depression Among People Affected by versus P...

DOI :10.12659/MSM.924609

Med Sci Monit 2020; 26:e924609

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750