Effect of the echinocandin caspofungin on expression of Candida albicans secretory aspartyl proteinases and phospholipase in vitro.
Although the echinocandin caspofungin primarily inhibits the synthesis of cell wall 1,3-beta-D-glucan, its fungicidal activity could also potentially perturb the expression of virulence factors involved in the ability of Candida albicans to cause infection. Expression of the C. albicans secretory aspartyl proteinase (SAP) and phospholipase B (PLB) virulence genes was determined by reverse transcription-PCR after the addition of caspofungin to cells grown for 15 h in Sabouraud dextrose broth. In cells that remained viable, expression of SAP1 to SAP3, SAP7 to SAP9, and PLB1 was unaltered after exposure to fungicidal concentrations (4 to 16 micro g/ml) of caspofungin over a period of 7 h. However, expression of SAP5 increased steadily beginning 1 h after exposure to caspofungin. These results indicate that caspofungin is rapidly fungicidal against C. albicans, before any suppression of SAP or PLB1 gene expression can occur.
Department of Microbiology and Immunology, Faculty of Medicine, University of Montreal, Quebec, Canada.
Jean-Sébastien
JS
Ripeau
Francine
F
Aumont
Pierre
P
Belhumeur
Luis
L
Ostrosky-Zeichner
John H
JH
Rex
Louis
L
de Repentigny
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D000077336:Caspofungin; D054714:Echinocandins; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005800:Genes, Fungal / Q000235:genetics; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D010455:Peptides; D010456:Peptides, Cyclic; D010740:Phospholipases / Q000096:biosynthesis* / Q000235:genetics; D012331:RNA, Fungal / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D012331:RNA, Fungal; D012333:RNA, Messenger; D010740:Phospholipases; D016282:Aspartic Acid Endopeptidases; D000077336:Caspofungin