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Is metabolic generalism the Breakfast of Champions for pathogenic Candida species?

Summary

This review examines how different Candida species, including the common cause of yeast infections (C. albicans) and the more dangerous bloodstream pathogen (C. glabrata), survive in the human body. While most pathogenic Candida species are metabolic generalists that can eat many different nutrients, the review shows that C. glabrata is a specialist that has found alternative strategies to thrive. Understanding these metabolic strategies is important for developing better treatments and fighting antifungal resistance.

Background

Metabolic generalism refers to an organism’s ability to utilize diverse nutrients and adapt to dynamic environmental conditions. For Candida species, this versatility is crucial for survival and virulence in diverse host niches. Understanding metabolic strategies in pathogenic Candida is essential for comprehending their pathogenesis.

Objective

This review explores major metabolic themes supporting Candida species pathogenesis and examines how the metabolic specialist Candida glabrata provides insights into metabolic determinants critical for host survival. The paper investigates whether metabolic generalism is truly essential for pathogenic Candida species or if alternative strategies can support virulence.

Results

C. albicans demonstrates metabolic flexibility through rewired ubiquitination targets allowing simultaneous glycolysis and alternative carbon source utilization. C. glabrata, despite being a metabolic specialist, exhibits significant adaptability through efficient utilization of non-fermentable carbon sources and relies heavily on mitochondrial respiration. Petite mutants lacking functional mitochondria can paradoxically show increased virulence in certain contexts.

Conclusion

While metabolic generalism is typically associated with Candida pathogenesis, metabolic specialism in C. glabrata demonstrates that alternative strategies can support survival in host environments. The winning metabolic strategy likely involves balancing rapid proliferation under permissive conditions with maintenance of metabolically inactive subpopulations for antifungal tolerance, and further research is needed to understand species-specific metabolic adaptations.
  • Published in:PLoS Pathogens,
  • Study Type:Review,
  • Source: PMID: 39661646, DOI: 10.1371/journal.ppat.1012752
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