title: KRE genes are required for beta-1,6-glucan synthesis, maintenance of capsule architecture and cell wall protein anchoring in Cryptococcus neoformans.
abstract: The polysaccharide beta-1,6-glucan is a major component of the cell wall of Cryptococcus neoformans, but its function has not been investigated in this fungal pathogen. We have identified and characterized seven genes, belonging to the KRE family, which are putatively involved in beta-1,6-glucan synthesis. The H99 deletion mutants kre5Delta and kre6Deltaskn1Delta contained less cell wall beta-1,6-glucan, grew slowly with an aberrant morphology, were highly sensitive to environmental and chemical stress and were avirulent in a mouse inhalation model of infection. These two mutants displayed alterations in cell wall chitosan and the exopolysaccharide capsule, a primary cryptococcal virulence determinant. The cell wall content of the GPI-anchored phospholipase B1 (Plb1) enzyme, which is required for cryptococcal cell wall integrity and virulence, was reduced in kre5Delta and kre6Deltaskn1Delta. Our results indicate that KRE5, KRE6 and SKN1 are involved in beta-1,6-glucan synthesis, maintenance of cell wall integrity and retention of mannoproteins and known cryptococcal virulence factors in the cell wall of C. neoformans. This study sets the stage for future investigations into the function of this abundant cell wall polymer.
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Gilbert
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Donlin
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Gerik
authors.forename: Charles A
authors.initials: CA
authors.lastname: Specht
authors.forename: Julianne T
authors.initials: JT
authors.lastname: Djordjevic
authors.forename: Christabel F
authors.initials: CF
authors.lastname: Wilson
authors.forename: Tania C
authors.initials: TC
authors.lastname: Sorrell
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Lodge
mesh_terms: D000818:Animals; D001108:Architecture; D002473:Cell Wall / Q000378:metabolism*; D003453:Cryptococcosis / Q000382:microbiology / Q000473:pathology; D003455:Cryptococcus neoformans / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D008283:Maintenance; D051379:Mice; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding; D016019:Survival Analysis; D014774:Virulence; D047071:beta-Glucans / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D011134:Polysaccharides; D047071:beta-Glucans; C064197:beta-1,6-glucan
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