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Updated: Feb 9, 2026

Size Matters: Measurement of Capsule Diameter in Cryptococcus neoformans
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Size Matters: Measurement of Capsule Diameter in Cryptococcus neoformans

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Miltefosine Has a Postantifungal Effect and Induces Apoptosis in Cryptococcus Yeasts

Cristina de Castro Spadari1, Taissa Vila2, Sonia Rozental3

  • 1Laboratório de Quimioterapia Antifúngica, Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.

Antimicrobial Agents and Chemotherapy
|May 31, 2018
PubMed

Insights

Miltefosine (MFS) shows antifungal activity against Cryptococcus by disrupting cell membranes and inducing apoptosis. This drug has potential for treating cryptococcosis, especially in HIV patients, with a notable post-antifungal effect on fungal proliferation.

Area of Science:

  • Mycology
  • Antifungal Drug Discovery
  • Cellular Biology

Background:

  • Cryptococcus species are significant opportunistic fungal pathogens, posing a threat particularly to individuals with compromised immune systems, such as those with HIV/AIDS.
  • Miltefosine (MFS), an approved drug, exhibits potential as an alternative antifungal agent for treating cryptococcosis, but its precise mechanism of action against Cryptococcus remains unclear.

Purpose of the Study:

  • To elucidate the mechanism of action of miltefosine (MFS) against Cryptococcus neoformans and Cryptococcus gattii.
  • To evaluate the efficacy of MFS against both planktonic and biofilm forms of Cryptococcus yeasts.

Main Methods:

  • Assessed the inhibitory and fungicidal effects of MFS on planktonic and biofilm cultures of C. neoformans and C. gattii.
  • Investigated the post-antifungal effect (PAFE) of MFS on Cryptococcus proliferation.
  • Utilized transmission electron microscopy and measured plasma membrane permeability, mitochondrial membrane potential, and reactive oxygen species (ROS) production.

Main Results:

  • MFS demonstrated inhibitory and fungicidal activity against planktonic and dispersed biofilm Cryptococcus cells, with reduced sensitivity in sessile biofilm cells.
  • A significant post-antifungal effect was observed, delaying proliferation for up to 8.15 hours after short MFS exposure.
  • MFS increased plasma membrane permeability (likely via ergosterol interaction), reduced mitochondrial membrane potential, elevated ROS, and induced apoptosis, alongside morphological changes like capsule reduction and cell wall alterations.

Conclusions:

  • Miltefosine exhibits fungicidal activity against Cryptococcus by disrupting membrane integrity and inducing apoptosis, suggesting a multi-targeted mechanism.
  • The drug's effectiveness against planktonic and dispersed biofilm cells, coupled with its post-antifungal effect, highlights its therapeutic potential for cryptococcosis.
  • Further clinical studies are warranted to establish MFS treatment protocols for cryptococcosis.
Keywords:
Cryptococcusapoptosisergosterolfungicidal effectmembrane permeabilitymiltefosinemitochondriapostantifungal effect

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