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Antifungal Effects of the Phloroglucinol Derivative DPPG Against Pathogenic Aspergillus fumigatus

Summary

Scientists developed a new antifungal compound called DPPG based on a natural antibacterial molecule produced by soil bacteria. This synthetic derivative showed strong activity against dangerous fungal pathogens like Aspergillus fumigatus and Candida species, which cause serious infections in humans. The compound works by disrupting the fungal cell membrane, causing it to leak and die. Testing in insect models demonstrated effectiveness comparable to current clinical antifungal medications.

Background

Fungal infections pose a significant threat to human and animal health, with increasing antifungal drug resistance complicating treatment. Natural products and their derivatives have shown promise as novel antifungal agents. This study investigates a phloroglucinol derivative (DPPG) based on 2,4-diacetylphloroglucoside (DAPG), a compound produced by Pseudomonas fluorescens with known antimicrobial properties.

Objective

To assess the antifungal activity of DPPG against pathogenic Aspergillus and Candida species, elucidate its mechanism of action against A. fumigatus, and evaluate its therapeutic efficacy in an in vivo infection model.

Results

DPPG demonstrated significantly improved antifungal activity compared to DAPG, with MIC values of 16-128 μg/mL against Candida species and 16-64 μg/mL against Aspergillus species. DPPG inhibited hyphal growth and spore germination in a dose-dependent manner and disrupted fungal membrane integrity without inducing ROS accumulation. In the G. mellonella model, DPPG showed therapeutic efficacy comparable to amphotericin B.

Conclusion

DPPG is a potent phloroglucinol-based scaffold with broad-spectrum antifungal activity against clinically important fungi. Its mechanism involves membrane perturbation and cellular content leakage rather than ROS-dependent pathways, representing a novel approach to combat invasive fungal infections.
  • Published in:Antibiotics (Basel),
  • Study Type:Experimental Research,
  • Source: PMID: 40426565, DOI: 10.3390/antibiotics14050499
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