Antifungal Pharmacology and Fungal Cell Wall Biochemistry

The treatment of invasive fungal infections hinges on a delicate exploitation of differences between fungal pathogens and their human hosts. Central to this endeavour is the unique composition and architecture of the fungal cell wall, which comprises an inner scaffold of β-1,3-glucan and chitin interwoven with mannoproteins. Antifungal pharmacology has thus focused on disrupting cell membrane integrity or cell wall assembly. Polyenes bind ergosterol to form disruptive pores, azoles and allylamines inhibit key enzymes in ergosterol biosynthesis, while echinocandins block β-1,3-glucan synthase. Despite these advances, the limited number of drug classes and the eukaryotic kinship of fungi have fostered rising resistance and toxicity concerns. Recent efforts have turned to novel agents that target chitin synthase or synergise established drugs to overcome resistant strains, alongside exploration of natural product libraries and synthetic scaffolds. Underlying this pharmacological evolution is detailed knowledge of cell wall biochemistry, which informs how combinations of β-glucan and chitin inhibition can yield fungicidal activity. A robust understanding of the interplay between cell wall architecture, enzyme kinetics, and drug pharmacodynamics is therefore essential to guide the next generation of antifungal regimens with improved efficacy and safety profiles.

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Antifungal Pharmacology and Fungal Cell Wall Biochemistry publication trend

The graph below shows the total number of articles in antifungal pharmacology and fungal cell wall biochemistry across all publications each year (not limited to Nature Index journals).

Technical terms

Echinocandins: A class of antifungal agents that inhibit β-1,3-glucan synthase, weakening fungal cell wall integrity.

Chitin Synthase: An enzyme responsible for polymerising N-acetylglucosamine into chitin, a rigid polysaccharide in fungal cell walls.

β-1,3-Glucan: A polymer of glucose units forming the primary structural scaffold of the fungal cell wall.

Ergosterol: A sterol component of fungal cell membranes targeted by polyenes and inhibitors of its biosynthesis.

Fungicidal vs Fungistatic: Describes whether an antifungal agent kills fungi outright (fungicidal) or merely inhibits their growth (fungistatic).

References

1. In Vitro Killing Activities of Anidulafungin and Micafungin with and without Nikkomycin Z against Four Candida auris Clades. Pharmaceutics (2023).
2. Evaluation of nikkomycin Z with frequent oral administration in an experimental model of central nervous system coccidioidomycosis. Microbiology Spectrum (2024).
3. Sources of Antifungal Drugs. Journal of Fungi (2023).