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J Biol Chem. 2020 Feb 14;295(7):1815-1828. doi: 10.1074/jbc.RA119.011949. Epub 2020 Jan 2.

Melanin deposition in two Cryptococcus species depends on cell-wall composition and flexibility.

Author information

1
Department of Chemistry and Biochemistry, City College of New York and CUNY Institute for Macromolecular Assemblies, New York, New York 10031.
2
Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, New York 10016.
3
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205.
4
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10033.
5
Department of Preventive Medicine and Public Health and Microbiology, Autonoma University of Madrid, 28049 Madrid, Spain.
6
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110.
7
Department of Chemistry and Biochemistry, City College of New York and CUNY Institute for Macromolecular Assemblies, New York, New York 10031 rstark@ccny.cuny.edu.
8
Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, New York 10016.

Abstract

Cryptococcus neoformans and Cryptococcus gattii are two species complexes in the large fungal genus Cryptococcus and are responsible for potentially lethal disseminated infections. These two complexes share several phenotypic traits, such as production of the protective compound melanin. In C. neoformans, the pigment associates with key cellular constituents that are essential for melanin deposition within the cell wall. Consequently, melanization is modulated by changes in cell-wall composition or ultrastructure. However, whether similar factors influence melanization in C. gattii is unknown. Herein, we used transmission EM, biochemical assays, and solid-state NMR spectroscopy of representative isolates and "leaky melanin" mutant strains from each species complex to examine the compositional and structural factors governing cell-wall pigment deposition in C. neoformans and C. gattii. The principal findings were the following. 1) C. gattii R265 had an exceptionally high chitosan content compared with C. neoformans H99; a rich chitosan composition promoted homogeneous melanin distribution throughout the cell wall but did not increase the propensity of pigment deposition. 2) Strains from both species manifesting the leaky melanin phenotype had reduced chitosan content, which was compensated for by the production of lipids and other nonpolysaccharide constituents that depended on the species or mutation. 3) Changes in the relative rigidity of cell-wall chitin were associated with aberrant pigment retention, implicating cell-wall flexibility as an independent variable in cryptococcal melanin assembly. Overall, our results indicate that cell-wall composition and molecular architecture are critical factors for the anchoring and arrangement of melanin pigments in both C. neoformans and C. gattii species complexes.

KEYWORDS:

Cryptococcus; cell wall; fungi; melanin; molecular structure; nuclear magnetic resonance (NMR); opportunistic pathogen; polysaccharide; solid state NMR; virulence factor

PMID:
31896575
DOI:
10.1074/jbc.RA119.011949

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