Serum and glycerol regulate yeast-hypha dimorphism in Benjaminiella poitrasii by modulating glutamate dehydrogenase gene expression

Abstract Purpose Dimorphic switching between yeast and hypha is a key virulence trait in many pathogenic fungi. The non-pathogenic zygomycete, Benjaminiella poitrasii , also undergoes yeast-to-hypha transitions in response to pH, temperature, and glucose, and is an established model for fungal dimorphism. However, the role of serum, a major inducer in pathogenic fungi, has not been investigated in B. poitrasii . Methods Whole-cell extracts of yeast and hyphal cells were assayed for NAD- and NADP-dependent glutamate dehydrogenase (GDH) activity by monitoring NAD(P)H oxidation at 340 nm. Total RNA from yeast and hyphal forms was isolated at different time points, converted to cDNA, and analyzed for the expression of NAD- and NADP-GDH and glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ) using RT-PCR and RT-qPCR. Results Serum and glycerol, similar to their effect in Candida albicans , induced the yeast-to-hypha transition in B. poitrasii . Expression analysis revealed a 0.6-fold induction of yeast-specific BpNADPGDH I in glycerol ( p < 0.0001), while serum preferentially enhanced hypha-specific BpNADPGDH II ( p < 0.005), resulting in a 2.3-fold increase in gene expression. These transcriptional patterns were validated by corresponding changes in GDH enzyme activities. Conclusions Multiple triggers, including temperature, glucose, and serum, appear to converge on a shared signaling pathway governing dimorphism in B. poitrasii . Notably, serum exerted a dominant influence over glucose in promoting yeast-to-hypha transition. Although considered non-pathogenic, B. poitrasii shows metabolic adaptability and serum-driven morphogenesis, paralleling pathogenic fungi. Given that its close relative, B. youngii , is pathogenic, these traits raise the possibility of B. poitrasii emerging as an opportunistic pathogen. Graphical Abstract