Five Pmt isoforms O-mannosylate secretory proteins in Candida albicans. Comparisons of genome-wide transcript patterns of each pmt mutant revealed commonly downregulated genes involved in glycolysis and glycerol production. Increased phosphorylation of the Cek1p- but not the Mkc1p-MAP kinase, as well as increased transcript levels for some stress-related genes were detected in the pmt1 strain but not in the other pmt mutants. The transcriptomal pattern after short-term inhibition of Pmt1p activity confirmed stress responses, but did not indicate an alteration of glycolytic flow. Short- but not long-term adaptation to Pmt1p inhibition required signalling components Cek1p, Mkc1p, Efg1p and Tpk1p. Cna1p (calcineurin) but not its downstream effectors Crz1p and Crz2p was generally essential to allow growth during Pmt1p inhibition; accordingly, cyclosporin A strongly inhibited growth of the pmt1 mutant. The lack of Pmt isoforms influenced transcript levels for the remaining isoforms both positively and negatively, suggesting complex cross-regulation among PMT genes. These results confirm individual functions of Pmt isoforms but suggest a common biphasic adaptation response to Pmt deficiency. While known signalling pathways modulate adaptation for a short-term, long-term adaptation requires calcineurin, adjustments of remaining Pmt activities and of glycolytic flow.