Lithium-mediated suppression of morphogenesis and growth in Candida albicans.
Hyphal development in Candida albicans contributes to virulence, and inhibition of filamentation is a target for the development of antifungal agents. Lithium is known to impair Saccharomyces cerevisiae growth in galactose-containing media by inhibition of phosphoglucomutase, which is essential for galactose metabolism. Lithium-mediated phosphoglucomutase inhibition is reverted by Mg(2+). In this study we have assessed the effect of lithium upon C. albicans and found that growth is inhibited preferentially in galactose-containing media. No accumulation of glucose-1-phosphate or galactose-1-phosphate was detected when yeasts were grown in the presence of galactose and 15 mM LiCl, though we observed that in vitro lithium-mediated phosphoglucomutase inhibition takes place with an IC(50) of 2 mM. Furthermore, growth inhibition by lithium was not reverted by Mg(2+). These results show that lithium-mediated inhibition of growth in a galactose-containing medium is not due to inhibition of galactose conversion to glucose-6-phosphate but is probably due to inhibition of a signaling pathway. Deletion of the Ser-Thr protein phosphatase SIT4 and treatment with rapamycin have been shown to inhibit filamentous differentiation. We observed that C. albicans filamentation was inhibited by lithium in solid medium containing either galactose as the sole carbon source or 10% fetal bovine serum. These results suggest that suppression of hyphal outgrowth by lithium could be related to inhibition of the target of rapamycin (TOR) pathway.
Martins
Layla F
LF
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
Montero-Lomelí
Monica
M
Masuda
Claudio A
CA
Fortes
Fabio S A
FS
Previato
Jose O
JO
Mendonça-Previato
Lucia
L
D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development*; D003470:Culture Media / Q000737:chemistry; D005690:Galactose / Q000378:metabolism; D005695:Galactosephosphates / Q000032:analysis; D017353:Gene Deletion; D005958:Glucosephosphates / Q000032:analysis; D025301:Hyphae / Q000187:drug effects / Q000254:growth & development; D020128:Inhibitory Concentration 50; D008094:Lithium / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism; D010733:Phosphoglucomutase / Q000037:antagonists & inhibitors; D054648:Protein Phosphatase 2 / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology
D000935:Antifungal Agents; D003470:Culture Media; D005695:Galactosephosphates; D005958:Glucosephosphates; D029701:Saccharomyces cerevisiae Proteins; C029973:galactose-1-phosphate; D008094:Lithium; C031590:glucose-1-phosphate; D054648:Protein Phosphatase 2; C104343:SIT4 protein, S cerevisiae; D010733:Phosphoglucomutase; D008274:Magnesium; D020123:Sirolimus; D005690:Galactose