| Autor: |
Yee EA; Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556.; E Arsenault Yee and RL Ross contributed equally to this work, and order was determined by who initiated the study (EAY) and who brought it to completion (RLR)., Ross RL; Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556.; E Arsenault Yee and RL Ross contributed equally to this work, and order was determined by who initiated the study (EAY) and who brought it to completion (RLR)., Santiago-Tirado FH; Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556.; Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana 46556.; Warren Center for Drug Discovery, University of Notre Dame, Notre Dame, Indiana 46556. |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 31. Date of Electronic Publication: 2024 Mar 31. |
| DOI: |
10.1101/2023.09.18.558251 |
| Abstrakt: |
Cryptococcus neoformans is a fungal pathogen responsible for >200,000 yearly cases with a mortality as high as 81%. This burden results, in part, from an incomplete understanding of its pathogenesis and ineffective antifungal treatments; hence, there is a pressing need to understand the biology and host interactions of this yeast to develop improved treatments. Protein palmitoylation is important for cryptococcal virulence, and we previously identified the substrates of its main palmitoyl transferase. One of them was encoded by the uncharacterized gene CNAG_02129. In the filamentous fungus Neurospora crassa , a homolog of this gene named HAM-13 plays a role in proper cellular communication and filament fusion. In Cryptococcus , cellular communication is essential during mating, therefore we hypothesized that CNAG_02129, which we named HAM1 , may play a role in mating. We found that ham1 Δ mutants produce more fusion products during mating, filament more robustly, and exhibit competitive fitness defects under mating and non-mating conditions. Additionally, we found several differences with the major virulence factor, the polysaccharide capsule, that may affect virulence, consistent with prior studies linking virulence to mating. We observed that ham1 Δ mutants have decreased capsule attachment and transfer but exhibit higher amounts of exopolysaccharide shedding and biofilm production. Lastly, HAM1 expression is significantly lower in mating media relative to non-mating conditions, consistent with it acting as a negative regulator of mating. Understanding the connection between mating and virulence in C. neoformans may open new avenues of investigation into ways to improve the treatment of this disease. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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