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Antifungal drugs acting via new mechanisms of action are urgently needed to combat the increasing numbers of severe fungal infections caused by pathogens such as  Candida albicans . The phosphopantetheinyl transferase of  Aspergillus fumigatus , encoded by the essential gene  pptB , has previously been identified as a potential antifungal target. This study investigated the function of its orthologue in  C .  albicans ,  PPT2 /C1_09480W by placing one allele under the control of the regulatable  MET3  promoter, and deleting the remaining allele. The phenotypes of this conditional null mutant showed that, as in  A .  fumigatus , the gene  PPT2  is essential for growth in  C .  albicans , thus fulfilling one aspect of an efficient antifungal target. The catalytic activity of Ppt2 as a phosphopantetheinyl transferase and the acyl carrier protein Acp1 as a substrate were demonstrated in a fluorescence transfer assay, using recombinant Ppt2 and Acp1 produced and purified from  E . coli . A fluorescence polarisation assay amenable to high-throughput screening was also developed. Therefore we have identified Ppt2 as a broad-spectrum novel antifungal target and developed tools to identify inhibitors as potentially new antifungal compounds.

Characterisation of the Candida albicans Phosphopantetheinyl Transferase Ppt2 as a Potential Antifungal Drug Target