Transcriptional and physiological adaptation to defective protein-O-mannosylation in Candida albicans

Area of Science:

• Biochemistry
• Molecular Biology
• Mycology

Background:

• Protein O-mannosylation is crucial for fungal cell wall integrity and virulence in Candida albicans.
• Five Pmt (protein O-mannosyltransferase) isoforms are responsible for O-mannosylation in C. albicans.
• The specific roles and regulatory mechanisms of individual Pmt isoforms are not fully understood.

Purpose of the Study:

• To investigate the functions of individual Pmt isoforms in Candida albicans.
• To elucidate the adaptive responses to Pmt deficiency at the transcriptomal and signaling levels.
• To identify key signaling pathways involved in short-term and long-term adaptation to Pmt inhibition.

Main Methods:

• Construction and analysis of genome-wide transcript patterns for single pmt mutants.
• Analysis of MAP kinase phosphorylation and stress-related gene expression.
• Short-term inhibition of Pmt1p activity and subsequent transcriptomal analysis.
• Assessment of adaptation requirements using signaling component mutants and calcineurin inhibition.

Main Results:

• Common downregulation of glycolysis and glycerol production genes observed in pmt mutants.
• Specific stress responses and altered Cek1p phosphorylation in the pmt1 mutant.
• Short-term adaptation to Pmt1p inhibition involves Cek1p, Mkc1p, Efg1p, and Tpk1p.
• Long-term adaptation requires calcineurin (Cna1p) and adjustments in glycolytic flow and remaining Pmt activities.
• Complex cross-regulation observed among PMT gene isoforms.

Conclusions:

• Pmt isoforms have both individual functions and complex cross-regulatory interactions.
• Candida albicans exhibits a biphasic adaptation response to Pmt deficiency.
• Short-term adaptation relies on known signaling pathways, while long-term adaptation involves calcineurin and metabolic adjustments.