title: Role of Cln1 during melanization of Cryptococcus neoformans.
abstract: Cryptococcus neoformans is an opportunistic fungal pathogen that has several well-described virulence determinants. A polysaccharide capsule and the ability to produce melanin are among the most important. Melanization occurs both in vitro, in the presence of catecholamine and indole compounds, and in vivo during the infection. Despite the importance of melanin production for cryptococcal virulence, the component and mechanisms involved in its synthesis have not been fully elucidated. In this work, we describe the role of a G1/S cyclin (Cln1) in the melanization process. Cln1 has evolved specifically with proteins present only in other basidiomycetes. We found that Cln1 is required for the cell wall stability and production of melanin in C. neoformans. Absence of melanization correlated with a defect in the expression of the LAC1 gene. The relation between cell cycle elements and melanization was confirmed by the effect of drugs that cause cell cycle arrest at a specific phase, such as rapamycin. The cln1 mutant was consistently more susceptible to oxidative damage in a medium that induces melanization. Our results strongly suggest a novel and hitherto unrecognized role for C. neoformans Cln1 in the expression of virulence traits.
authors: Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III Majadahonda, Spain.
authors: Rocío
authors: R
authors: García-Rodas
authors: Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III Majadahonda, Spain.
authors: Nuria
authors: N
authors: Trevijano-Contador
authors: Department of Microbiology, Pharmacy Faculty, Complutense University of Madrid Madrid, Spain.
authors: Elvira
authors: E
authors: Román
authors: Unité Biologie et Pathogénicité Fongiques, Institut Pasteur Paris, France.
authors: Guilhem
authors: G
authors: Janbon
authors: Unité Biologie et Pathogénicité Fongiques, Institut Pasteur Paris, France.
authors: Frédérique
authors: F
authors: Moyrand
authors: Department of Microbiology, Pharmacy Faculty, Complutense University of Madrid Madrid, Spain.
authors: Jesús
authors: J
authors: Pla
authors: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA.
authors: Arturo
authors: A
authors: Casadevall
authors: Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III Majadahonda, Spain.
authors: Oscar
authors: O
authors: Zaragoza
keywords: Cryptococcus CLN1; cell wall; laccase; melanin