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In-depth evaluation of the acetylome in major human fungal pathogens elucidates the essential role of lysine acetylation in regulation of fungal pathogenicity

ABSTRACT: Fungal pathogens cause deadly diseases in living organisms. Numerous studies suggest that lysine acetylation is a critical regulator in pathogenic fungi, but an in-depth and cross-species analysis of the acetylome in major pathogenic fungi is lacking, and our knowledge of the mechanism of acetylation in manipulating fungal pathogenicity is limited. Here, we show that lysine acetylation plays essential roles during cryptococcosis through modulating the gene expression of important virulence factors and the activity of key players in important pathways. We show that the Cryptococcus TOR pathway and translational elongation process are functionally regulated by acetylation via the HDAC and sirtuin families, respectively. Through comparative acetylome network analysis among pathogens and baker’s yeast, we demonstrate significant correlation between acetylation sites and virulence factors, indicating a unique selective pressure on lysine acetylation motifs in pathogenic fungi. These results provide a basis for understanding the regulation of fungal pathogenicity by posttranslational lysine acetylation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Cryptococcus Neoformans Var. Grubii Serotype A (strain H99 / Atcc 208821 / Cbs 10515 / Fgsc 9487) (filobasidiella Neoformans Var. Grubii)

TISSUE(S): Fungal Cell

DISEASE(S): Fungal Meningitis

SUBMITTER: Hai-Long Li

LAB HEAD: Cheney Ding

PROVIDER: PXD010354 | Pride | 2019-04-29

REPOSITORIES: Pride

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Project description:Around two-thirds of all plant species form arbuscular mycorrhizasa symbiosis between plant roots and glomalean fungi that leads to the formation of intraradical organs of nutrient exchange and an extraradical network of fungal hyphae effectively extending the plant root system. The mycorrhiza plays a key role in plant nutrition and in enhancing plant resistance against pathogens and improving drought resistance. At present very little is known about the molecular basis of arbuscular mycorrhiza formation. Arabidopsis thaliana (as with all Brassicaceae) does not form arbuscular mycorrhizas (AM). Arabidopsis may either have lost essential gene functions or acquired new ones that prevent a successful symbiotic interaction. However given that mycorrhizal symbiosis developed very early during the evolution of land plants and that many ectomycorrhizal plant species can be colonised by AM fungi it is likely that important components of AM signalling pathways are conserved in all plants including Arabidopsis. Possibly the lack of AM development is a multigenic trait and this would make it difficult to isolate mutants that (re-)gain the ability to interact with AM fungi. What can be done however is firstly to test which parts of one or several putative AM signalling pathways are still functional and which ones are not. Secondly we can test whether negatively acting pathways such as those involved in defence against pathogenic microorganisms are induced upon inoculation with AM fungi. Together this work is likely to give important information of why Arabidopsis (and Brassicaceae) are behaving as non-hosts for AM fungi. In other words Arabidopsis will be an ideal system to study mechanisms of non-host "resistance" to AM colonisation. Elucidating these mechanisms will obviously make a great contribution to understanding the basis of the mycorrhizal interaction. Moreover using Arabidopsis as a tool it will be possible at the end to integrate the information obtained for AM signalling with that obtained for other developmental and environmentally triggered signalling pathways such as plant hormone signalling or plant defence responses. To produce an inventory of which Arabidopsis genes respond at all to inoculation with AM fungi a genome-wide screen for AM-controlled genes is proposed. RNA will be prepared from Arabidopsis roots treated with AM fungus and mock-inoculated control plants. Arabidopsis (Col-0) will be grown in pot culture (1:1 sand/Terra-Green) at low concentrations of phosphate. Three week-old plants will be inoculated with surface-sterilised spores of Gigaspora rosea. RNA will be isolated 3 days post inoculation. Experimenter name: Hsiu-Ling Yap; Experimenter phone: 01904 434 302/304; Experimenter fax: 01904 434 312; Experimenter institute: University of York; Experimenter address: Department of Biology; University of York; P.O.Box 373; York!Series_summary = Experimenter zip/postal_code: YO10 5YW; Experimenter country: UK Experiment Overall Design: 4 samples were used in this experiment

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In-depth evaluation of the acetylome in major human fungal pathogens elucidates the essential role of lysine acetylation in regulation of fungal pathogenicity

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