The influence of ketoconazole on the activity of asparagine protease produced by Candida strains

Piotr Kurnatowski1, Arkadiusz Grabek

  • 1Department of Biology and Medical Parasitology, Medical University of L6di, Hallera 1, Lódź, Poland.

Research Communications in Molecular Pathology and Pharmacology
|June 15, 2007
PubMed

Insights

Antimycotic drug resistance is increasing in pathogenic fungi like Candida. This study shows ketoconazole alters fungal sensitivity and asparagine protease activity over time, offering insights into drug resistance mechanisms.

Area of Science:

  • Medical Mycology
  • Antimicrobial Resistance

Background:

  • Pathogenic fungi, particularly Candida species, exhibit decreasing sensitivity to antimycotic drugs.
  • Fungal strains from patients display non-standard enzymatic activity, necessitating further investigation.
  • Understanding the in vitro effects of antimycotic drugs on fungal exoenzymes is crucial.

Purpose of the Study:

  • To evaluate the in vitro influence of ketoconazole on the drug sensitivity of patient-isolated fungal strains over three weeks.
  • To assess the changes in asparagine protease activity in fungal strains exposed to ketoconazole.
  • To develop a model for analyzing the development of reduced antimycotic drug sensitivity in vitro.

Main Methods:

  • Fungal cultures were exposed daily to ketoconazole at 2, 4, and 6 times the minimal inhibitory concentration (MIC) for three weeks.
  • Asparagine protease activity was measured before, during (1, 2, and 3 weeks), and after ketoconazole administration.
  • Statistical analysis was performed to determine significant changes in drug activity and enzyme levels.

Main Results:

  • Ketoconazole treatment over three weeks significantly altered the drug response curves of Candida strains, indicated by changes in MIC values.
  • Asparagine protease activity decreased after one week of ketoconazole administration and increased after two and three weeks.

Conclusions:

  • Ketoconazole exposure in vitro can modify the sensitivity of Candida strains to antimycotic drugs.
  • Changes in asparagine protease activity correlate with ketoconazole administration, suggesting a role in drug resistance.
  • The study provides a model for investigating the in vitro development of reduced fungal sensitivity to antimycotic agents.

Related Concept Videos

Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...
Candidiasis01:20

Candidiasis

Candidiasis is a fungal infection caused by opportunistic species of Candida. It can affect various anatomical sites, including the skin, oral cavity, nails, and genitourinary tract. Among its forms, vaginal candidiasis is the most common type of mucosal infection. It typically results from the overgrowth of Candida albicans in the vaginal mucosa. Under normal conditions, C. albicans exists as a commensal organism within the vaginal microbiota, regulated by the dominance of lactobacilli, which...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates these...