Depletion of the Candida albicans TLO gene family reveals a requirement for alpha TLO genes for wild-type virulence

Candida albicans is usually a harmless member of the human microbiome. However, it is also one of the most important causes of fungal disease in humans, especially in individuals with compromised immune systems. The reasons for the shift from harmless commensal to pathogen are complex. We have previously shown that a unique expansion of a gene family, called TLO, plays a role in the pathogenesis of C. albicans infections. The proteins encoded by the 10-14 copies of the TLO genes present in the C. albicans genome are components of the Mediator complex, which plays an important role in the control of gene expression. To try and investigate the functionality of specific TLO genes, we have generated mutant strains that only express a single TLO gene (i.e. TLO2 and TLO5). Analysis of these mutants shows that they display distinct morphologies and growth characteristics that affect their virulence. We also show that reintroducing the TLO alpha 1 gene into these mutants results in a restoration of growth and virulence defects. Our data provide further evidence that there is functional diversity within the TLO gene family and suggest that there may be competition between alpha- and gamma-clade Tlo proteins.