title: Distinct roles of cell wall biogenesis in yeast morphogenesis as revealed by multivariate analysis of high-dimensional morphometric data.
abstract: The cell wall of budding yeast is a rigid structure composed of multiple components. To thoroughly understand its involvement in morphogenesis, we used the image analysis software CalMorph to quantitatively analyze cell morphology after treatment with drugs that inhibit different processes during cell wall synthesis. Cells treated with cell wall-affecting drugs exhibited broader necks and increased morphological variation. Tunicamycin, which inhibits the initial step of N-glycosylation of cell wall mannoproteins, induced morphologies similar to those of strains defective in α-mannosylation. The chitin synthase inhibitor nikkomycin Z induced morphological changes similar to those of mutants defective in chitin transglycosylase, possibly due to the critical role of chitin in anchoring the β-glucan network. To define the mode of action of echinocandin B, a 1,3-β-glucan synthase inhibitor, we compared the morphology it induced with mutants of Fks1 that contains the catalytic domain for 1,3-β-glucan synthesis. Echinocandin B exerted morphological effects similar to those observed in some fks1 mutants, with defects in cell polarity and reduced glucan synthesis activity, suggesting that echinocandin B affects not only 1,3-β-glucan synthesis, but also another functional domain. Thus our multivariate analyses reveal discrete functions of cell wall components and increase our understanding of the pharmacology of antifungal drugs.
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba 277-8561, Japan Instituto de Biología Funcional y Genómica and Departamento de Microbiología y Genética, CSIC/Universidad de Salamanca, 37007 Salamanca, Spain Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11794.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Okada
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ohnuki
authors.forename: Cesar
authors.initials: C
authors.lastname: Roncero
authors.forename: James B
authors.initials: JB
authors.lastname: Konopka
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ohya
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D048430:Cell Shape / Q000187:drug effects* / Q000235:genetics; D002473:Cell Wall / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D002687:Chitin Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D054714:Echinocandins / Q000494:pharmacology; D005656:Fungal Proteins / Q000494:pharmacology; D009024:Morphogenesis / Q000235:genetics*; D009154:Mutation; D012441:Saccharomyces cerevisiae; D012984:Software; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D000617:Aminoglycosides; D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D014415:Tunicamycin; C011952:nikkomycin; C007572:echinocandin B; D002687:Chitin Synthase