Pathogenic Mechanisms of Candida Glabrata

Candida glabrata has emerged as a leading opportunistic fungal pathogen, second only to C. albicans in invasive candidiasis. Unlike its more morphologically versatile counterparts, C. glabrata remains in a yeast form, relying on a repertoire of cell surface adhesins to bind host tissues and to assemble resilient biofilms on abiotic surfaces, such as indwelling medical devices. Once attached, the organism withstands oxidative and nitrosative stress through robust stress‐response pathways and deploys aspartyl proteases to subvert epithelial and immune cell signalling, thereby dampening cytokine release and neutrophil recruitment. Within macrophages, C. glabrata exhibits an ability to survive and replicate, governed by dynamic transcriptional programmes that also underpin its intrinsic tolerance to azole and echinocandin antifungals. Metabolic plasticity is further illustrated by the petite phenotype, where loss of mitochondrial function confers drug tolerance and distinct host‐inflammatory interactions, albeit at the cost of in vivo fitness. Collectively, these attributes—adhesion, immune evasion, intracellular persistence, transcriptional regulation and drug tolerance—shape a stealthy strategy of evasion and persistence that poses significant challenges in immunocompromised patients and underscores the global importance of novel therapeutic targets.

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Pathogenic Mechanisms of Candida Glabrata publication trend

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Technical terms

Adhesin: A cell‐surface protein that mediates fungal attachment to host tissues or abiotic surfaces.

Biofilm: A structured community of fungal cells embedded in an extracellular matrix, often resistant to antifungal agents.

Echinocandin: A class of antifungal drugs that inhibit the synthesis of β-1,3-glucan in fungal cell walls.

Macrophage: A type of host immune cell that engulfs and kills pathogens, including yeasts.

Transcription factor: A protein that binds DNA to regulate the expression of specific genes.

Aspartyl protease: An enzyme that cleaves peptide bonds, used by fungi to modulate host proteins and immune responses.

Petite phenotype: A mitochondrial‐deficient state in yeast associated with altered metabolism and drug tolerance.

References

1. Temporal transcriptional response of Candida glabrata during macrophage infection reveals a multifaceted transcriptional regulator CgXbp1 important for macrophage response and fluconazole resistance. eLife (2024).
2. Aspartyl proteases target host actin nucleator complex protein to limit epithelial innate immunity. EMBO Reports (2024).
3. Overlooked Candida glabrata petites are echinocandin tolerant, induce host inflammatory responses, and display poor in vivo fitness. mBio (2023).