title: Connecting virulence pathways to cell-cycle progression in the fungal pathogen Cryptococcus neoformans.
abstract: Proliferation and host evasion are critical processes to understand at a basic biological level for improving infectious disease treatment options. The human fungal pathogen Cryptococcus neoformans causes fungal meningitis in immunocompromised individuals by proliferating in cerebrospinal fluid. Current antifungal drugs target "virulence factors" for disease, such as components of the cell wall and polysaccharide capsule in C. neoformans. However, mechanistic links between virulence pathways and the cell cycle are not as well studied. Recently, cell-cycle synchronized C. neoformans cells were profiled over time to identify gene expression dynamics (Kelliher et al., PLoS Genet 12(12):e1006453, 2016). Almost 20% of all genes in the C. neoformans genome were periodically activated during the cell cycle in rich media, including 40 genes that have previously been implicated in virulence pathways. Here, we review important findings about cell-cycle-regulated genes in C. neoformans and provide two examples of virulence pathways-chitin synthesis and G-protein coupled receptor signaling-with their putative connections to cell division. We propose that a "comparative functional genomics" approach, leveraging gene expression timing during the cell cycle, orthology to genes in other fungal species, and previous experimental findings, can lead to mechanistic hypotheses connecting the cell cycle to fungal virulence.
authors.affiliation: Department of Biology, Duke University, Box 90338, 130 Science Drive, Durham, NC, 27708-0338, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Kelliher
authors.affiliation: Department of Biology, Duke University, Box 90338, 130 Science Drive, Durham, NC, 27708-0338, USA. shaase@duke.edu.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Haase
mesh_terms: D002453:Cell Cycle; D002686:Chitin / Q000096:biosynthesis; D003453:Cryptococcosis / Q000382:microbiology*; D003455:Cryptococcus neoformans / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
chemical_list: D021122:Protein Subunits; D043562:Receptors, G-Protein-Coupled; D037521:Virulence Factors; D002686:Chitin
keywords: Cell-cycle transcription; Cryptococcus neoformans; Gene regulatory networks; Virulence factors