Phosphate starvation induces replacement of phospholipids with the betaine lipid diacylglycerol-N,N,N-trimethylhomoserine in the human fungal pathogen Candida albicans
Year: 2017
Type: preprint
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 ( Ca BTA1), which is activated during P i scarcity. The Ca BTA1 gene is also induced under certain biofilm-promoting conditions independent of P i starvation. RNA-seq and qRT-PCR showed a significant increase in Ca BTA1 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 hyphaeinducing media and observed defects in biofilm formation and invasive growth in the bta1ΔΔ mutant. This observation is complemented by RNA-seq data demonstrating that P i 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 .
DOI: 10.1101/199133
Institution: University of Nebraska–Lincoln
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2765634064