Scientists at Tulane University School of Medicine have made a significant breakthrough in studying a fungus that causes pneumonia, a disease that has been challenging to culture in a laboratory setting. The researchers utilized precision-cut lung tissue slices to examine Pneumocystis species, a fungus that mainly affects immunosuppressed individuals and children, causing Pneumocystis pneumonia.
The inability to effectively grow this particular pathogen outside of a living lung has greatly hindered fungal research and drug development. However, the development of this new model offers scientists a better opportunity to test potential medications and combat the infection. It is worth noting that the World Health Organization recently included Pneumocystis among the top 19 fungal priority pathogens.
Dr. Jay Kolls, the corresponding author and John W Deming Endowed Chair in Internal Medicine at Tulane, stated that Pneumocystis is likely the most common fungal pneumonia in children. However, the challenge of culturing this fungus has resulted in a lack of new antibiotics for over two decades, as they have to be tested in animal studies.
The Tulane model utilizes precision-cut lung slices, which accurately replicate the complexity and structure of lung tissue, providing an environment that closely mimics the conditions inside the lung. The researchers applied this technique to successfully cultivate two forms of the Pneumocystis fungus, namely the troph and ascus, for up to 14 days. Through viability testing and gene expression analysis, it was observed that the fungus survived over time within the model.
This groundbreaking research marks the first time that both the trophic and ascus forms of Pneumocystis have been sustained outside of a mammalian host. Moreover, the model demonstrates its potential for in vitro drug testing. Treatment with the commonly used medications trimethoprim-sulfamethoxazole and echinocandins resulted in a reduction in the expression of Pneumocystis genes, indicating successful targeting of the fungus.
One of the key advantages of the Tulane technique is its ability to generate numerous uniform lung tissue samples from a single lung, facilitating high-capacity testing. Dr. Kolls expressed optimism in the potential of precision lung slices to promote the growth of Pneumocystis and become a powerful tool for the development of new medications to treat the infection. This advancement could significantly accelerate research on this particular pathogen.
The study was led by Ferris T. Munyonho, a graduate student in Tulane’s Biomedical Sciences program. Munyonho, who previously obtained a Bachelor’s degree in Science from the University of Zimbabwe, is also a recipient of a Fulbright Scholarship.
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1. Source: Coherent Market Insights, Public sources, Desk research
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