title: Hydroxyurea enhances post-fusion hyphal extension during sexual development in C. neoformans var. grubii.
abstract: Mating and sexual development in C. neoformans var. grubii strains of the H99 background is often less robust than that laboratory generated isogenic C. neoformans var. neoformans strains in the JEC21 background. In Candida albicans and Saccharomyces serevisiae, slowing of DNA synthesis and engagement of the replication stress response, such as that caused by treatment with hydroxyurea (HU), induces filamentation and pseudohyphal growth, respectively. In this study, we investigated the effect of HU treatment on C. neoformans var. grubii morphogenesis. Treatment with HU did not induce filamentation of yeast cells either in liquid culture or on solid YPD or V8 agar. In the presence of the opposite mating partner, we observed early emergence of hyphae in the presence of HU. Semi-quantitative analysis of fusion using marked strains demonstrated that no significant enhancement of fusion in the presence of HU. Transfer of fusion colonies from crosses performed in the absence of HU to V8 + HU revealed enhanced hyphal growth in the presence of HU. Analysis of expression of the target of HU, ribonucleotide reductase, revealed that a phylogenetically divergent catalytic subunit is replication stress responsive in C. neoformans. These results suggest that induction of replication stress promotes post-fusion hyphal growth of C. neoformans var. grubii strains in the H99 background.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA.
authors.forename: M Naim
authors.initials: MN
authors.lastname: Zulkifli
authors.forename: Jan Naseer
authors.initials: JN
authors.lastname: Kaur
authors.forename: John C
authors.initials: JC
authors.lastname: Panepinto
mesh_terms: D000595:Amino Acid Sequence; D003455:Cryptococcus neoformans / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D006918:Hydroxyurea / Q000494:pharmacology*; D025301:Hyphae / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000187:drug effects; D010802:Phylogeny; D012098:Reproduction / Q000187:drug effects; D016415:Sequence Alignment; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005656:Fungal Proteins; D006918:Hydroxyurea