Sterol compositions and susceptibilities to amphotericin B of environmental Cryptococcus neoformans isolates are

B Currie1, H Sanati, A S Ibrahim

  • 1Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Insights

Host factors in persistent Cryptococcus neoformans meningoencephalitis can alter fungal sterol composition and reduce susceptibility to amphotericin B. This suggests human infection may select for drug-resistant fungal variants.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Pharmacology

Background:

  • Sequential isolates of *Cryptococcus neoformans* from patients with persistent meningoencephalitis exhibit variability in sterol composition and antifungal drug susceptibility.
  • Host factors may mediate these observed changes in fungal properties.

Purpose of the Study:

  • To investigate the role of host factors in mediating changes in fungal sterol composition and antifungal susceptibility.
  • To compare the antifungal susceptibilities of environmental and clinical isolates of *Cryptococcus neoformans*.

Main Methods:

  • Comparison of antifungal susceptibilities between environmental and clinical isolates.
  • In vivo passage of environmental isolates through BALB/c murine hosts.
  • Analysis of sterol composition and antifungal susceptibility of parent and passaged isolates.

Main Results:

  • Clinical isolates demonstrated lower susceptibility to amphotericin B compared to environmental isolates.
  • Murine passage of environmental isolates led to alterations in sterol composition and reduced amphotericin B susceptibility.
  • Fluconazole susceptibility remained unchanged after murine passage.

Conclusions:

  • Host factors can induce in vivo changes in fungal sterol composition and antifungal susceptibility.
  • Human infection with *Cryptococcus neoformans* may select for variants with diminished susceptibility to amphotericin B.

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