title: Glucan-associated protein modulations and ultrastructural changes of the cell wall in Candida albicans treated with micafungin, a water-soluble, lipopeptide antimycotic.
abstract: The composition of glucan-associated proteins (GAP) in the cell wall of Candida albicans was strongly affected by treatment with a sub-MIC yet beta-glucan synthesis inhibitory concentration (0.01 microg/ml) of FK463 (micafungin). Namely, a decrease in enzymes of glucose metabolism (mostly enolase and a novel 40 kDaltons component, here identified as the enzyme fructose-1,6-biphosphate aldolase) was observed, and this was coupled with an increase in two beta1-3 exo-glucanase isoforms (34 and 44 kDa, respectively). No GAP changes were detected in the same strain of the fungus made resistant to the drug, attesting to the specificity of the observed cell wall protein modulation. In addition, GAP changes were accompanied by marked ultrastructural alterations upon treatment with the sub-MIC dose of the drug, the majority of which was an aberrant cell surface morphology and a derangement of the normal layering of the cell wall. Our data demonstrate that sub-MIC doses of micafungin do critically affect not only the beta-glucan synthetic machinery but also protein composition and the whole cell wall structure of Candida albicans.
authors.affiliation: Institute of Microbiology, Faculty of Pharmacy,"Rossi Fanelli", University of Rome "La Sapienza", Rome, Italy. letizia.angiolella@uniroma1.it
authors.forename: L
authors.initials: L
authors.lastname: Angiolella
authors.forename: B
authors.initials: B
authors.lastname: Maras
authors.forename: A R
authors.initials: AR
authors.lastname: Stringaro
authors.forename: G
authors.initials: G
authors.lastname: Arancia
authors.forename: F
authors.initials: F
authors.lastname: Mondello
authors.forename: A
authors.initials: A
authors.lastname: Girolamo
authors.forename: A T
authors.initials: AT
authors.lastname: Palamara
authors.forename: A
authors.initials: A
authors.lastname: Cassone
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D054714:Echinocandins; D005656:Fungal Proteins / Q000187:drug effects / Q000378:metabolism; D005936:Glucans / Q000378:metabolism*; D006801:Humans; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology*; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012995:Solubility
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D005936:Glucans; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077551:Micafungin