New model could revolutionize antifungal drug testing

Researchers at Tulane University School of Medicine have devised a promising model for studying a pneumonia-causing fungus that has long eluded laboratory cultivation. Overcoming the challenge of growing Pneumocystis species outside a living lung, scientists utilized precision-cut lung tissue slices to investigate this fungus, a culprit behind Pneumocystis pneumonia in immunosuppressed patients and children.

This breakthrough addresses a significant obstacle in fungal research, opening avenues for testing new drugs against the infection. Pneumocystis, recently designated among the World Health Organization’s top 19 fungal priority pathogens, has posed challenges due to its resistance to cultivation, hindering antibiotic development for over two decades.

Dr. Jay Kolls, corresponding author and John W Deming Endowed Chair in Internal Medicine at Tulane, emphasized the model’s significance in mimicking lung conditions closely. The precision-cut lung slices maintained the complexity and architecture of lung tissue, allowing for the long-term cultivation of both trophic and ascus forms of Pneumocystis outside a mammalian host—an unprecedented achievement.

Viability testing and gene expression analysis affirmed the fungus’s survival in the model. The technique’s potential for in vitro drug testing was validated as commonly used medications reduced the expression of Pneumocystis genes, indicating effective targeting of the fungus.

Ferris T. Munyonho, a Tulane Biomedical Sciences graduate student and Fulbright Scholarship recipient, led the study. The Tulane technique, capable of generating numerous uniform lung tissue samples from a single lung, presents a high-capacity testing tool. Dr. Kolls envisions the optimized precision lung slices as a powerful tool for cultivating Pneumocystis and accelerating medication development for this infection.

Source: Tulane University

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