Sensitivity of Trichophyton mentagrophytes strains to three imidazole drugs

K Lenhart1, A Merkunová

  • 1Department of Medical Biology, Medical Faculty, Palacký University, Olomouc, Czechoslovakia.

Acta Universitatis Palackianae Olomucensis Facultatis Medicae
|January 1, 1991
PubMed

Insights

This study investigated the antifungal drug sensitivity of Trichophyton mentagrophytes strains. Ketoconazole-resistant mutants were successfully generated using UV radiation, demonstrating increased resistance upon repeated exposure.

Area of Science:

  • Medical Mycology
  • Antimicrobial Resistance

Background:

  • Dermatophytes like Trichophyton mentagrophytes cause superficial fungal infections.
  • Imidazole antifungal drugs are commonly used for treatment.
  • Understanding drug resistance mechanisms is crucial for effective therapy.

Purpose of the Study:

  • To assess the sensitivity of Trichophyton mentagrophytes strains to ketoconazole, miconazole, and clotrimazole.
  • To investigate the generation and characteristics of ketoconazole-resistant mutants.
  • To explore the correlation between ketoconazole's effect on fungal growth and ergosterol biosynthesis.

Main Methods:

  • Minimal Inhibitory Concentration (MIC) assay to determine drug sensitivity.
  • Induction of drug-resistant mutants using UV radiation.
  • Assessment of ergosterol biosynthesis inhibition.

Main Results:

  • Variability in imidazole drug sensitivity observed across strains (10^-2-10^0 µg/ml).
  • Ketoconazole-resistant mutants were generated with a frequency of 1.3 x 10^-7 per spore/nucleus.
  • Repeated UV exposure led to increased ketoconazole resistance.
  • No significant correlation found between ketoconazole's effect on mycelial growth and ergosterol biosynthesis.

Conclusions:

  • Trichophyton mentagrophytes exhibits variable sensitivity to common imidazole antifungals.
  • UV radiation is effective in generating ketoconazole-resistant mutants, highlighting potential resistance pathways.
  • Further research is needed to elucidate the mechanisms underlying ketoconazole resistance and its impact on ergosterol biosynthesis.

Related Concept Videos

Skin Diseases and Disorders01:23

Skin Diseases and Disorders

Skin is the first line of defense and encounters a variety of microbes. Some pathogenic strains are often the cause of a broad range of infections of the skin and other body systems. These conditions can affect people of all ages and may have different causes, including genetic factors, infections, autoimmune reactions, environmental factors, and lifestyle choices.
Gram-positive Staphylococcus spp. and Streptococcus spp. are responsible for many of the most common skin infections. However, many...
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...
Anthelminthic Agents01:15

Anthelminthic Agents

Anthelmintic drugs differ significantly from antiparasitic therapies targeting protozoa, primarily due to differences in parasite biology. Whereas most protozoal treatments act on proliferating cells, anthelmintics are typically directed against mature, nonproliferative helminths. The therapeutic approach considers the helminth's reliance on neuromuscular coordination, glucose metabolism, and microtubular integrity for survival, reproduction, and localization within the host. Most anthelmintics...
Antiprotozoal Agents01:21

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...