Discovery of highly reactive self-splicing group II introns within the mitochondrial genomes of human pathogenic...

Area of Science:

• Molecular biology
• Mycology
• Bioinformatics

Background:

• Fungal pathogens pose increasing health risks with limited treatment options.
• Self-splicing group II introns are potential antifungal drug targets but their distribution in fungi is poorly understood.

Purpose of the Study:

• To develop a bioinformatic method for identifying group II introns in pathogenic fungi.
• To characterize the distribution, structure, and reactivity of these introns.
• To assess the potential of these introns as antifungal drug targets.

Main Methods:

• Developed a bioinformatic workflow to scan sequence data for group II intron structural signatures.
• Analyzed sequence data from thermally dimorphic fungi (Blastomyces, Coccidioides, Histoplasma).
• Assessed intron self-splicing activity and inhibition by mitoxantrone in vitro.

Main Results:

• Discovered ubiquitous group II introns in Blastomyces, Coccidioides, and Histoplasma.
• These introns exhibit the highest biochemical reactivity reported for group II introns.
• Introns self-splice rapidly under physiological conditions without protein cofactors.
• Demonstrated in vitro inhibition of these introns by the FDA-approved drug mitoxantrone.

Conclusions:

• Structure-based bioinformatic searches are effective for identifying regulatory RNA elements in pathogens.
• Ubiquitous, highly reactive self-splicing group II introns in pathogenic fungi represent promising antifungal drug targets.
• These findings open new avenues for developing novel antifungal therapies.