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Identification of a major IP(5) kinase in Cryptococcus neoformans confirms that PP-IP(5)/IP(7), not IP(6), is essential for virulence

Fungal inositol polyphosphate (IP) kinases catalyse phosphorylation of IP(3) to inositol pyrophosphate, PP-IP(5)/IP(7), which is essential for virulence of Cryptococcus neoformans. Cryptococcal Kcs1 converts IP(6) to PP-IP(5)/IP(7), but the kinase converting IP(5) to IP(6) is unknown. Deletion of a...

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Autores principales: Li, Cecilia, Lev, Sophie, Saiardi, Adolfo, Desmarini, Desmarini, Sorrell, Tania C., Djordjevic, Julianne T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817067/
https://www.ncbi.nlm.nih.gov/pubmed/27033523
http://dx.doi.org/10.1038/srep23927
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author Li, Cecilia
Lev, Sophie
Saiardi, Adolfo
Desmarini, Desmarini
Sorrell, Tania C.
Djordjevic, Julianne T.
author_facet Li, Cecilia
Lev, Sophie
Saiardi, Adolfo
Desmarini, Desmarini
Sorrell, Tania C.
Djordjevic, Julianne T.
author_sort Li, Cecilia
collection PubMed
description Fungal inositol polyphosphate (IP) kinases catalyse phosphorylation of IP(3) to inositol pyrophosphate, PP-IP(5)/IP(7), which is essential for virulence of Cryptococcus neoformans. Cryptococcal Kcs1 converts IP(6) to PP-IP(5)/IP(7), but the kinase converting IP(5) to IP(6) is unknown. Deletion of a putative IP(5) kinase-encoding gene (IPK1) alone (ipk1Δ), and in combination with KCS1 (ipk1Δkcs1Δ), profoundly reduced virulence in mice. However, deletion of KCS1 and IPK1 had a greater impact on virulence attenuation than that of IPK1 alone. ipk1Δkcs1Δ and kcs1Δ lung burdens were also lower than those of ipk1Δ. Unlike ipk1Δ, ipk1Δkcs1Δ and kcs1Δ failed to disseminate to the brain. IP profiling confirmed Ipk1 as the major IP(5) kinase in C. neoformans: ipk1Δ produced no IP(6) or PP-IP(5)/IP(7) and, in contrast to ipk1Δkcs1Δ, accumulated IP(5) and its pyrophosphorylated PP-IP(4) derivative. Kcs1 is therefore a dual specificity (IP(5) and IP(6)) kinase producing PP-IP(4) and PP-IP(5)/IP(7). All mutants were similarly attenuated in virulence phenotypes including laccase, urease and growth under oxidative/nitrosative stress. Alternative carbon source utilisation was also reduced significantly in all mutants except ipk1Δ, suggesting that PP-IP(4) partially compensates for absent PP-IP(5)/IP(7) in ipk1Δ grown under this condition. In conclusion, PP-IP(5)/IP(7), not IP(6), is essential for fungal virulence.
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spelling pubmed-48170672016-04-05 Identification of a major IP(5) kinase in Cryptococcus neoformans confirms that PP-IP(5)/IP(7), not IP(6), is essential for virulence Li, Cecilia Lev, Sophie Saiardi, Adolfo Desmarini, Desmarini Sorrell, Tania C. Djordjevic, Julianne T. Sci Rep Article Fungal inositol polyphosphate (IP) kinases catalyse phosphorylation of IP(3) to inositol pyrophosphate, PP-IP(5)/IP(7), which is essential for virulence of Cryptococcus neoformans. Cryptococcal Kcs1 converts IP(6) to PP-IP(5)/IP(7), but the kinase converting IP(5) to IP(6) is unknown. Deletion of a putative IP(5) kinase-encoding gene (IPK1) alone (ipk1Δ), and in combination with KCS1 (ipk1Δkcs1Δ), profoundly reduced virulence in mice. However, deletion of KCS1 and IPK1 had a greater impact on virulence attenuation than that of IPK1 alone. ipk1Δkcs1Δ and kcs1Δ lung burdens were also lower than those of ipk1Δ. Unlike ipk1Δ, ipk1Δkcs1Δ and kcs1Δ failed to disseminate to the brain. IP profiling confirmed Ipk1 as the major IP(5) kinase in C. neoformans: ipk1Δ produced no IP(6) or PP-IP(5)/IP(7) and, in contrast to ipk1Δkcs1Δ, accumulated IP(5) and its pyrophosphorylated PP-IP(4) derivative. Kcs1 is therefore a dual specificity (IP(5) and IP(6)) kinase producing PP-IP(4) and PP-IP(5)/IP(7). All mutants were similarly attenuated in virulence phenotypes including laccase, urease and growth under oxidative/nitrosative stress. Alternative carbon source utilisation was also reduced significantly in all mutants except ipk1Δ, suggesting that PP-IP(4) partially compensates for absent PP-IP(5)/IP(7) in ipk1Δ grown under this condition. In conclusion, PP-IP(5)/IP(7), not IP(6), is essential for fungal virulence. Nature Publishing Group 2016-04-01 /pmc/articles/PMC4817067/ /pubmed/27033523 http://dx.doi.org/10.1038/srep23927 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Li, Cecilia
Lev, Sophie
Saiardi, Adolfo
Desmarini, Desmarini
Sorrell, Tania C.
Djordjevic, Julianne T.
Identification of a major IP(5) kinase in Cryptococcus neoformans confirms that PP-IP(5)/IP(7), not IP(6), is essential for virulence
title Identification of a major IP(5) kinase in Cryptococcus neoformans confirms that PP-IP(5)/IP(7), not IP(6), is essential for virulence
title_full Identification of a major IP(5) kinase in Cryptococcus neoformans confirms that PP-IP(5)/IP(7), not IP(6), is essential for virulence
title_fullStr Identification of a major IP(5) kinase in Cryptococcus neoformans confirms that PP-IP(5)/IP(7), not IP(6), is essential for virulence
title_full_unstemmed Identification of a major IP(5) kinase in Cryptococcus neoformans confirms that PP-IP(5)/IP(7), not IP(6), is essential for virulence
title_short Identification of a major IP(5) kinase in Cryptococcus neoformans confirms that PP-IP(5)/IP(7), not IP(6), is essential for virulence
title_sort identification of a major ip(5) kinase in cryptococcus neoformans confirms that pp-ip(5)/ip(7), not ip(6), is essential for virulence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817067/
https://www.ncbi.nlm.nih.gov/pubmed/27033523
http://dx.doi.org/10.1038/srep23927
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