MYCOLab Ai Logo - gold and army green

The Candida albicans transcription factor Efg1 governs hyphal morphogenesis independently of the cAMP-protein kinase A pathway

Summary

Scientists studied how Candida albicans, a common fungal infection, switches between yeast and filamentous forms. The long-accepted explanation was that a protein signal (PKA) activates a key regulator called Efg1 by adding a chemical tag. However, this new research shows that this mechanism is not actually required for the fungus to change shape, form biofilms, or cause disease in mice, suggesting scientists need to find the real mechanism controlling this critical process.

Background

Candida albicans is a common human fungal pathogen that causes both superficial mucosal and invasive disease. The ability to transition between yeast and filamentous morphologies is a key virulence trait. A long-standing model proposes that the cAMP-protein kinase A pathway phosphorylates the transcription factor Efg1 to drive filamentation.

Objective

To reinvestigate the protein kinase A-Efg1 paradigm by examining whether phosphorylation of Efg1 at threonine 208 (T208) by PKA is necessary for filamentation, biofilm formation, and virulence. The study used updated genetic approaches to test this 25-year-old mechanistic model.

Results

No evidence was found that blocking or mimicking PKA phosphorylation at Efg1 T208 affected filamentation under diverse in vitro conditions, biofilm formation, in vivo filamentation, or virulence in a disseminated candidiasis model. RNA-seq analysis showed no differentially expressed genes between strains with WT or phosphorylation-deficient Efg1 alleles.

Conclusion

The study demonstrates that PKA-mediated phosphorylation of Efg1 at T208 is not essential for hyphal morphogenesis, biofilm formation, or virulence, challenging a foundational paradigm in C. albicans research. These negative findings highlight a knowledge gap regarding how Efg1 is actually regulated during filamentation and warrant future studies to identify alternative regulatory mechanisms.
  • Published in:mBio,
  • Study Type:Experimental Study,
  • Source: PMID: 41170998, DOI: 10.1128/mbio.02913-25
Scroll to Top