Review 2: "The Riboflavin Biosynthetic Pathway as a Novel Target for Antifungal Drugs Against Candida Species"

RR\ID Evidence Scale rating by reviewer:

• Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review: This is an exciting report of how genes for the flavin biosynthesis pathway in C. albicans are important virulence factors to consider as future potential drug targets.  With the increasing rise of drug resistant fungi, these studies are important.  My only concern with this report is the assay they are using to monitor riboflavin.  Fluorescence at 530 nm is not specific to riboflavin and FAD and FMN also emit at this wavelength. This is of particular concern with investigations of intracellular flavins, where studies in bakers’ yeast have shown the vast majority (95%) of flavins and fluorescence at 530 is due to FAD and FMN, not riboflavin. The authors need to take into account that much of what they are investigating could be non-riboflavin flavins. Still, the findings of the biosynthetic pathway and possible riboflavin importer are exciting and interesting.