MYCOLab Ai Logo - gold and army green

Deubiquitinase Ubp5 is essential for pulmonary immune evasion and hematogenous dissemination of Cryptococcus neoformans

Summary

Researchers studied a protein called Ubp5 that helps the fungus Cryptococcus neoformans cause disease in humans. By removing this protein, the fungus became much less harmful and the immune system could fight it better. The fungus with the missing protein had problems with its outer coating, couldn’t hide as well from the immune system, and couldn’t spread to the brain. This suggests that blocking Ubp5 could be a new way to help the body defend against this dangerous fungal infection.

Background

Cryptococcosis is a serious opportunistic fungal infection affecting immunocompromised populations, with Cryptococcus neoformans being the primary pathogenic species. The ubiquitin system plays critical roles in fungal virulence, and deubiquitinases like Ubp5 regulate important cellular processes including ribosomal biogenesis and protein degradation.

Objective

This study investigates the role of deubiquitinase Ubp5 in modulating host defenses and facilitating C. neoformans dissemination during pulmonary and systemic infections. The researchers aimed to determine how Ubp5 deletion affects fungal virulence, immune responses, and dissemination mechanisms.

Results

Ubp5 deletion significantly reduced pulmonary invasion and extrapulmonary dissemination, with mice showing prolonged survival and reduced fungal burdens. The attenuated virulence was associated with enhanced protective Th1/Th17 immune responses, lymphocyte-dominated lung infiltration, and reduced expression of virulence factors including capsule and melanin. Ubp5 deletion also caused morphological abnormalities and reduced ribosomal particles, impairing protein synthesis.

Conclusion

Ubp5 is essential for C. neoformans pulmonary invasion and dissemination through maintaining virulence factors, morphological stability, and immune evasion capabilities. Targeting Ubp5 represents a potential therapeutic strategy to enhance host immunity against cryptococcosis by promoting protective adaptive immune responses and limiting fungal dissemination.
  • Published in:Mycology,
  • Study Type:Experimental Animal Study,
  • Source: PMID: 40937134, DOI: 10.1080/21501203.2025.2453739
Scroll to Top