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Volume 172, Issue 1

Depletion of the gene family reveals a requirement for alpha genes for wild-type virulence Open Access

Abstract

uniquely possesses an expanded family of genes (the gene family) that encodes 10–15 paralogues of the Med2 component of the transcriptional regulator Mediator. Previous studies have shown that null mutants are unable to form hyphae and are hypersensitive to environmental stress. However, the reason for the gene expansion remains unclear, and the current study aimed to determine if reduction in the family copy number affected virulence. In order to investigate this, we used CRISPR-Cas9 mutagenesis to generate two -depleted mutants: one mutant retaining only β (CaTLO2) and the second mutant containing only γ (CaTLO5). Both -depleted mutants exhibited increased filamentous growth, increased susceptibility to specific stresses and reduced virulence in a murine model of oropharyngeal candidiasis (OPC). , the CaTLO5 mutant also exhibited impaired hyphal escape from macrophages and reduced hyphal invasion of oral keratinocytes. We then investigated if complementation with α, a gene previously shown to restore wild-type growth in a Δ null mutant, could restore virulence. infection models showed that α could restore true hypha formation, epithelial invasion and hyphal escape from macrophages in the CaTLO5 background. The murine OPC model showed that α could restore wild-type virulence in both CaTLO2 and CaTLO5 strains, suggesting an essential role for α- in oral mucosal infection. Together, these findings highlight the functional specialization between the α, β and γ gene groups and establish α- as a major regulator of virulence in .

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Candida albicans , gene expression , TLO genes and virulence
Funding
This study was supported by the:
  • Deutsche Forschungsgemeinschaft (Award SPP2225)
    • Principal Award Recipient: BernhardHube
  • National Institute of Dental and Craniofacial Research (Award R01DE030130)
    • Principal Award Recipient: SumantPuri
  • Science Foundation Ireland (Award 19/FFP/6642)
    • Principal Award Recipient: GaryP. Moran
© 2026 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2026-01-16
2026-03-06

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/content/journal/micro/10.1099/mic.0.001654
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Depletion of the Candida albicans TLO gene family reveals a requirement for alpha TLO genes for wild-type virulence
Microbiology 172, 001654 (2026); https://doi.org/10.1099/mic.0.001654
/content/journal/micro/10.1099/mic.0.001654
/content/journal/micro/10.1099/mic.0.001654
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