KRE genes are required for β‐1,6‐glucan synthesis,maintenance of capsule architecture and cell wall protein anchoring in Cryptococcus neoformans |
| |
Authors: | Nicole M. Gilbert Maureen J. Donlin Kimberly J. Gerik Charles A. Specht Julianne T. Djordjevic Christabel F. Wilson Tania C. Sorrell Jennifer K. Lodge |
| |
Affiliation: | 1. Edward A. Doisy Department of Biochemistry and Molecular Biology, and;2. Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA.;3. Department of Molecular Microbiology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.;4. Department of Medicine, University of Massachusetts, Worcester, MA 01605, USA.;5. Centre for Infectious Diseases and Microbiology,;6. ICPMR and;7. Westmead Millennium Institute, University of Sydney at Westmead Hospital, Sydney, NSW 2145, Australia. |
| |
Abstract: | The polysaccharide β‐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 β‐1,6‐glucan synthesis. The H99 deletion mutants kre5Δ and kre6Δskn1Δ contained less cell wall β‐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 kre5Δ and kre6Δskn1Δ. Our results indicate that KRE5, KRE6 and SKN1 are involved in β‐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. |
| |
Keywords: | |
|
|