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Biolistic Transformation of a Fluorescent Tagged Gene into the Opportunistic Fungal Pathogen Cryptococcus neoformans
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Liposomal Methylglyoxal Targets Virulence and Intracellular Persistence to Overcome Amphotericin B Resistance in

Masood Alam Khan1, Arif Khan1, Mohd Azam2

  • 1Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia.

International Journal of Molecular Sciences
|June 12, 2026
PubMed

Insights

Methylglyoxal (MG) shows promise as a novel antifungal treatment for cryptococcosis, outperforming Amphotericin B. Liposomal MG effectively targets virulence and intracellular infections with improved safety, offering a new therapeutic option.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Nanomedicine

Background:

  • Cryptococcosis is a significant cause of mortality in immunocompromised individuals.
  • Current treatments like Amphotericin B face challenges due to drug resistance and toxicity.
  • There is a need for novel antifungal strategies targeting virulence factors.

Purpose of the Study:

  • To evaluate methylglyoxal (MG) as a virulence-targeted antifungal agent for cryptococcosis.
  • To assess the efficacy and safety of liposomal MG (Lip-MG) delivery.
  • To investigate MG's mechanism of action against Cryptococcus neoformans.

Main Methods:

  • In vitro assessment of MG's antifungal activity, including MIC, biofilm inhibition, and laccase activity.
  • Evaluation of intracellular antifungal activity within macrophages.
  • In vivo studies using a leukopenic mouse model of systemic cryptococcosis.
  • Comparative analysis of Lip-MG, free MG, and Amphotericin B formulations.

Main Results:

  • MG demonstrated superior antifungal activity compared to Amphotericin B, with lower MIC values.
  • Lip-MG significantly inhibited biofilm formation and laccase activity, key virulence factors.
  • MG exhibited potent intracellular activity, and Lip-MG reduced fungal burden in macrophages.
  • Lip-MG significantly improved survival and reduced pulmonary fungal burden in mice, outperforming Amphotericin B.
  • MG formulations showed a favorable safety profile with lower nephrotoxicity than Amphotericin B.

Conclusions:

  • Liposomal methylglyoxal (Lip-MG) offers a dual-action, virulence-targeted approach for cryptococcosis treatment.
  • Lip-MG effectively eliminates intracellular infections and demonstrates improved safety compared to Amphotericin B.
  • MG-based nanotherapy presents a promising alternative for managing drug-resistant cryptococcosis.
Keywords:
antifungal therapybiofilmscryptococcusdrug-resistantlaccasenanoparticle

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