title: Members of protein O-mannosyltransferase family in Aspergillus fumigatus differentially affect growth, morphogenesis and viability.
abstract: O-mannosylation is an essential protein modification in eukaryotes. It is initiated at the endoplasmic reticulum by O-mannosyltransferases (PMT) that are evolutionary conserved from yeast to humans. The PMT family is phylogenetically classified into PMT1, PMT2 and PMT4 subfamilies, which differ in protein substrate specificity and number of genes per subfamily. In this study, we characterized for the first time the whole PMT family of a pathogenic filamentous fungus, Aspergillus fumigatus. Genome analysis showed that only one member of each subfamily is present in A. fumigatus, PMT1, PMT2 and PMT4. Despite the fact that all PMTs are transmembrane proteins with conserved peptide motifs, the phenotype of each PMT deletion mutant was very different in A. fumigatus. If disruption of PMT1 did not reveal any phenotype, deletion of PMT2 was lethal. Disruption of PMT4 resulted in abnormal mycelial growth and highly reduced conidiation associated to significant proteomic changes. The double pmt1pmt4 mutant was lethal. The single pmt4 mutant exhibited an exquisite sensitivity to echinocandins that is associated to major changes in the expression of signal transduction cascade genes. These results indicate that the PMT family members play a major role in growth, morphogenesis and viability of A. fumigatus.
authors.affiliation: Unité des Aspergillus, Institut Pasteur, 25 rue du Docteur Roux 75724 Paris Cedex 15, France. imouyna@pasteur.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mouyna
authors.forename: Olaf
authors.initials: O
authors.lastname: Kniemeyer
authors.forename: Thomas
authors.initials: T
authors.lastname: Jank
authors.forename: Céline
authors.initials: C
authors.lastname: Loussert
authors.forename: Emilia
authors.initials: E
authors.lastname: Mellado
authors.forename: Vishukumar
authors.initials: V
authors.lastname: Aimanianda
authors.forename: Anne
authors.initials: A
authors.lastname: Beauvais
authors.forename: Dirk
authors.initials: D
authors.lastname: Wartenberg
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Sarfati
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Prévost
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
authors.forename: Sabine
authors.initials: S
authors.lastname: Strahl
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Latgé
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D054714:Echinocandins / Q000494:pharmacology; D005656:Fungal Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D006801:Humans; D007527:Isoenzymes / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008364:Mannosyltransferases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D009154:Mutation; D025282:Mycelium / Q000378:metabolism / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D007527:Isoenzymes; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase