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. KhalafACDEFMed 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, 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
Editorial
01 July 2022 : Editorial
Editorial: World Health Organization (WHO) Variants of Concern Lineages Under Monitoring (VOC-LUM) in Response to the Global Spread of Lineages and Sublineages of Omicron, or B.1.1.529, SARS-CoV-2DOI: 10.12659/MSM.937676
Med Sci Monit 2022; 28:e937676
SARS-CoV-2/COVID-19
27 June 2022 : Clinical Research
Shoulder Injury Related to Vaccine Administration (SIRVA) in 16 Patients Following COVID-19 Vaccination Who...Med Sci Monit In Press; DOI: 10.12659/MSM.937430
04 June 2022 : Clinical Research
Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...Med Sci Monit 2022; 28:e936962
30 May 2022 : Clinical Research
Effects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...Med Sci Monit 2022; 28:e936069
27 May 2022 : Clinical Research
Factors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)Med Sci Monit 2022; 28:e936547
In Press
05 Jul 2022 : Clinical Research
Attention-Deficit/Hyperactivity Disorder (ADHD) and Time Perception in Adults: Do Adults with Different ADH...Med Sci Monit In Press; DOI: 10.12659/MSM.936849
01 Jul 2022 : Clinical Research
Does Early-Period Patient Dissatisfaction Turn Into Satisfaction Over Time After Total Knee Replacement?Med Sci Monit In Press; DOI: 10.12659/MSM.936792
30 Jun 2022 : Laboratory Research
Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human...Med Sci Monit In Press; DOI: 10.12659/MSM.936760
30 Jun 2022 : Clinical Research
Antioxidant System and Ions Concentrations After Femoral Neck and Resurfacing Hip ArthroplastyMed Sci Monit In Press; DOI: 10.12659/MSM.936335
Most Viewed Current Articles
30 Dec 2021 : Clinical Research
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...DOI :10.12659/MSM.935379
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review article
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...DOI :10.12659/MSM.936292
Med Sci Monit 2022; 28:e936292
13 Nov 2021 : Clinical Research
Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...DOI :10.12659/MSM.932788
Med Sci Monit 2021; 27:e932788
01 Nov 2020 : Review article
Long-Term Respiratory and Neurological Sequelae of COVID-19DOI :10.12659/MSM.928996
Med Sci Monit 2020; 26:e928996