A calmodulin inhibitor blocks morphogenesis in Candida albicans

Abstract

A calmodulin inhibitor, trifluoperazine (TFP), can block yeast‐to‐germ‐tube morphogenesis of Candida albicans induced by N‐acetyl‐d‐glucosamine at 37°C. Furthermore, the ionophore A23187 can also block germ tube formation, which can be reversed by Ca2+. This indicates the possible involvement of calcium and calmodulin in morphogenesis of C. albicans. During germ tube formation, there is a progressive increase in the rate of protein phosphorylation, which is completely absent in non‐germinating cells (yeast form). Trifluoperazine can also inhibit this phosphorylation indicating that protein phosphorylation may also be involved in this process.

Calcium signaling is involved in diverse cellular processes in fungi

“…Immunofluorescence assay of the GFP-tagged cam1 protein in S. pombe indicated the localisation of the Cam1 to the spindle body fibres and also to the sites responsible for polarised cell growth (Moser et al 1997 ; Itadani et al 2010 ). Calmodulin also mediates protein phosphorylation via calmodulin-dependent kinase in the presence of N -acetyl-D-glucosamine (GlcNAc), which is involved in germ tube formation causing morphogenesis of C. albicans ; however, calmodulin inhibitor trifluoperazine (TFP) inhibits the phosphorylation and germ tube formation (Roy and Datta 1987 ; Paranjape et al 1990 ). In addition, calmodulin binds to an integral membrane protein Dfi1p that activates mitogen-activated protein kinase (MAPK) Cek1p, which is required for invasive filamentation in C. albicans (Davis et al 2013 ).…”

Phosphorylation of glucosamine-6-phosphate synthase is important but not essential for germination and mycelial growth of Candida albicans

“…Unfortunately, little is known about the molecular mechanism of Y ! A participation of several secondary messenger systems in regulation of C. albicans dimorphism is suggested, including those based on cAMP [7], Ca 2þ /calmodulin or inositol phosphates [8][9][10] or control of intracellular pH [11]. It is induced by very different environmental factors, such as: N-acetyl-D D -glucosamine (GlcNAc) as the only carbon source, elevated temperature, neutral pH, presence of serum, proteins or abundant amino acids [5,6].…”

Roles of Ca2+ in hyphal and yeast-form growth in Candida albicans. Growth regulation by altered extracellular and intracellular free Ca2+ concentrations

“…In C. albicans, the involvement of Ca 2+ in the transition from the yeast form to the hyphal form has been pointed out by several authors. Treatment of cells with various calmodulin inhibitors, or the Ca 2 § ionophore A23187, which causes leakage of intracellular Ca 2 § to the medium, inhibited hyphal formation, implying that Ca 2+ acts as a positive regulator for hypha formation Roy and Datta, 1987;Sable and Gadd, 1989). On the other hand, hyphal formation occurred in synthetic media to which no calcium salt had been added and even in the presence of EGTA (Simonetti et al, 1974;Walker et al, 1984).…”