Phosphatases, together with kinases and transcription factors, are key components in cellular signalling networks. Here, we present a systematic functional analysis of the phosphatases in Cryptococcus neoformans, a fungal pathogen that causes life-threatening fungal meningoencephalitis. We analyse 230 signature-tagged mutant strains for 114 putative phosphatases under 30 distinct in vitro growth conditions, revealing at least one function for 60 of these proteins. Large-scale virulence and infectivity assays using insect and mouse models indicate roles in pathogenicity for 31 phosphatases involved in various processes such as thermotolerance, melanin and capsule production, stress responses, O-mannosylation, or retromer function. Notably, phosphatases Xpp1, Ssu72, Siw14, and Sit4 promote blood-brain barrier adhesion and crossing by C. neoformans. Together with our previous systematic studies of transcription factors and kinases, our results provide comprehensive insight into the pathobiological signalling circuitry of C. neoformans.
Bibliographical noteFunding Information:
This work was supported by the Strategic Initiative for Microbiomes in Agriculture and Food funded by the Ministry of Agriculture, Food and Rural Affairs (grant 916006-2 and 918012-4 to Y.-S.B.) and, in part, by National Research Foundation of Korea grants (grants 2016R1E1A1A01943365 and 2018R1A5A1025077 to Y.-S.B.; 2018R1C1B6009031 to K.-T.L.) from the Ministry of Science and ICT, and Brain Korea 21 (BK21) PLUS programme. This work was also supported by NIH/NIAID R37 MERIT award AI39115-21 and NIH/NIAID RO1 award AI50113-15 to J.H. J.H. is co-director and fellow CIFAR programme Fungal Kingdom: Threats & Opportunities.
© 2020, The Author(s).
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)