Antifungal Strategies in Biofilm-Forming Pathogens

Biofilms are structured communities of fungal cells embedded in a protective matrix that adhere to surfaces and exhibit heightened tolerance to conventional antifungal therapies. In clinical and industrial contexts, opportunistic pathogens such as Candida albicans form biofilms on mucosal tissues and indwelling devices, leading to persistent infections with considerable morbidity. Resistance mechanisms include restricted drug penetration by the extracellular matrix, elevated cell density, nutrient and oxygen gradients, overexpression of efflux pumps and the presence of dormant persister cells. Traditional agents—azoles, polyenes and echinocandins—frequently fail to eradicate biofilms, prompting exploration of alternative strategies. These encompass disruption of biofilm architecture by enzymes, inhibition of key virulence pathways such as hyphal development, utilisation of biosurfactant glycolipids, application of nanocarrier-mediated drug delivery and anti-virulence compounds. By targeting biofilm-specific processes, these approaches aim to restore antifungal susceptibility, mitigate device-associated and systemic mycoses and address a major global health challenge.

Research from Nature Portfolio

Studies have demonstrated the potential of biosurfactant glycolipids to prevent biofilm maturation and enhance drug efficacy. One investigation revealed that a sophorolipid markedly reduced Candida albicans biofilm biomass, disrupted hyphal differentiation and altered cell morphology under electron and confocal microscopy. When used alongside amphotericin B or fluconazole, the glycolipid acted synergistically against both forming and established biofilms. Gene expression analyses indicated downregulation of hypha-specific transcripts, suggesting interference with core virulence pathways. These findings support the integration of natural amphiphilic agents with standard antifungals to overcome biofilm recalcitrance.

Antifungal Strategies in Biofilm-Forming Pathogens publication trend

The graph below shows the total number of articles in antifungal strategies in biofilm-forming pathogens across all publications each year (not limited to Nature Index journals).

Technical terms

Biofilm: A community of microbial cells encased in a self-produced matrix that adheres to surfaces and exhibits increased resistance to antimicrobial agents.

Extracellular matrix: A polymeric network of polysaccharides, proteins and nucleic acids that embeds cells and limits diffusion of antifungal compounds.

Efflux pumps: Membrane transport proteins that actively export antifungal drugs from the cell interior, reducing intracellular drug concentration.

Hyphal development: The formation of elongated, filamentous structures by certain fungi that facilitate tissue invasion and biofilm maturation.

Persister cells: A subpopulation of metabolically dormant cells within a biofilm that survive lethal antifungal exposure and can repopulate the community.

Ras1-cAMP-Efg1 pathway: A signalling cascade governing morphological switching and gene expression essential for fungal virulence and biofilm formation.

References

1. Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development. International Journal of Oral Science (2023).
2. Synergistic activity of gold nanoparticles with amphotericin B on persister cells of Candida tropicalis biofilms. Journal of Nanobiotechnology (2024).
3. Inhibitory Effect of Sophorolipid on Candida albicans Biofilm Formation and Hyphal Growth. Scientific Reports (2016).