Candida albicans--do mycelia matter?

J F Ryley1, N G Ryley

  • 1ICI Pharmaceuticals, Mereside, Macclesfield, UK.

Insights

Mycelial growth of Candida albicans is not essential for kidney infection initiation or chronic colonization but aids in lesion development. Mycelia-less mutants showed altered kidney distribution and reduced antifungal drug susceptibility.

Area of Science:

  • Medical Mycology
  • Renal Pathogen Research

Background:

  • Candida albicans exhibits dimorphism, switching between yeast and mycelial forms.
  • The role of C. albicans mycelial growth in renal infection pathogenesis remains incompletely understood.

Purpose of the Study:

  • To investigate the necessity of Candida albicans mycelial growth for kidney infection initiation, colonization, and lesion development.
  • To compare the infectivity and antifungal susceptibility of wild-type C. albicans and its mycelia-less mutants in a murine kidney infection model.

Main Methods:

  • Intravenous inoculation of mice with wild-type C. albicans and two mycelia-less mutants (CA-2, MM2002).
  • Histopathological examination of kidneys to assess fungal distribution and inflammatory responses.
  • Evaluation of pyelonephritis and hydronephrosis.
  • Treatment of systemic infections with an azole antifungal (ICI 195,739) and amphotericin B to determine drug efficacy.

Main Results:

  • Mycelial growth was not essential for initial infection or chronic colonization but contributed to pelvic lesion formation.
  • Mycelia-less mutants localized primarily in glomeruli, unlike wild-type strains spreading throughout the cortex and medulla.
  • Mutants induced a milder inflammatory response compared to wild-type strains.
  • Chronic wild-type infections featured extensive mycelial masses in the renal pelvis.
  • Mutant infections were significantly less responsive to both azole and amphotericin B treatments compared to wild-type infections.

Conclusions:

  • Candida albicans mycelial development is crucial for pelvic lesion establishment but not for initial renal infection or chronic colonization.
  • Mycelia-less C. albicans mutants exhibit distinct kidney infection patterns and reduced susceptibility to antifungal therapies.
  • The in vivo efficacy of azole antifungals may involve mechanisms beyond the simple inhibition of mycelial growth.

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