Phosphate starvation induces replacement of phospholipids with the betaine lipid diacylglycerol-N,N,N-trimethylhomoserine in the human fungal pathogen Candida albicans

Authors

Surabhi Naik, University of Nebraska-LincolnFollow
Rebecca E. Cahoon, University of Nebraska-LincolnFollow
Bridget Tripp, University of Nebraska-LincolnFollow
Christian Elowsky, University of Nebraska-LincolnFollow
Sophie Alvarez, University of Nebraska-LincolnFollow
Kan Liu, University of Nebraska-LincolnFollow
Chi Zhang, University of Nebraska-LincolnFollow
Wayne R. Riekhof, University of Nebraska–LincolnFollow

Date of this Version

10-2017

Citation

bioRxiv preprint first posted online Oct. 16, 2017; doi: http://dx.doi.org/10.1101/199133.

Comments

CC-BY-NC-ND 4.0 International license.

Abstract

We have previously demonstrated that phosphate starvation induces replacement of phosphatidylcholine with the betaine lipid diacylglyceryl-N,N,N-trimethylhomoserine (DGTS) in fungi. In Neurospora crassa, the BTA1 gene encodes the betaine lipid synthase, which is necessary and sufficient for DGTS synthesis. BTA1 expression and DGTS accumulation are part of the fungal phosphorus (P_i) deprivation (PHO) regulon, mediated by the NUC-1/Pho4p transcription factor. We now demonstrate that the human pathogen Candida albicans encodes a BTA1 ortholog (CaBTA1), which is activated during P_i scarcity. The CaBTA1 gene is also induced under certain biofilm-promoting conditions independent of P_i starvation. RNA-seq and qRT-PCR showed a significant increase in CaBTA1 expression in response to P_i limitation. Thin-layer chromatography and LC-ESI-MS/MS confirmed the replacement of PC with DGTS in wild-type under low P_i and showed the absence of DGTS in the bta1ΔΔ mutant.

P_i limitation in the gut of critically ill patients also triggers the switching of C. albicans into an invasive filamentous form. To assess the role of BTA1 and DGTS in the pathogenicity of C. albicans in vitro, we compared the growth and morphology of bta1ΔΔ and wild type in hyphae-inducing media and observed defects in biofilm formation and invasive growth in the bta1ΔΔ mutant. This observation is complemented by RNA-seq data demonstrating that Pi starvation in planktonic C. albicans cells induces the expression of virulence-associated cell surface proteins. Taken together, these results show novel functional interactions between lipid metabolism and remodeling, biofilm formation, and the phosphate starvation response of C. albicans.