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Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans

The Mkt1–Pbp1 complex promotes mating-type switching by regulating the translation of HO mRNA in Saccharomyces cerevisiae. Here, we performed in vivo immunoprecipitation assays and mass spectrometry analyses in the human fungal pathogen Cryptococcus neoformans to show that Pbp1, a poly(A)-binding pr...

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Autores principales: Son, Ye-Eun, Fu, Ci, Jung, Won-Hee, Oh, Sang-Hun, Kwak, Jin-Hwan, Cardenas, Maria E., Heitman, Joseph, Park, Hee-Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811503/
https://www.ncbi.nlm.nih.gov/pubmed/31681631
http://dx.doi.org/10.3389/fcimb.2019.00355
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author Son, Ye-Eun
Fu, Ci
Jung, Won-Hee
Oh, Sang-Hun
Kwak, Jin-Hwan
Cardenas, Maria E.
Heitman, Joseph
Park, Hee-Soo
author_facet Son, Ye-Eun
Fu, Ci
Jung, Won-Hee
Oh, Sang-Hun
Kwak, Jin-Hwan
Cardenas, Maria E.
Heitman, Joseph
Park, Hee-Soo
author_sort Son, Ye-Eun
collection PubMed
description The Mkt1–Pbp1 complex promotes mating-type switching by regulating the translation of HO mRNA in Saccharomyces cerevisiae. Here, we performed in vivo immunoprecipitation assays and mass spectrometry analyses in the human fungal pathogen Cryptococcus neoformans to show that Pbp1, a poly(A)-binding protein-binding protein, interacts with Mkt1 containing a PIN like-domain. Association of Pbp1 with Mkt1 was confirmed by co-immunoprecipitation assays. Results of spot dilution growth assays showed that unlike pbp1 deletion mutant strains, mkt1 deletion mutant strains were not resistant to heat stress compared with wild-type. However, similar to the pbp1 deletion mutant strains, the mkt1 deletion mutants exhibited both, defective dikaryotic hyphal production and reduced pheromone gene (MFα1) expression during mating. In addition, deletion of mkt1 caused attenuated virulence in a murine intranasal inhalation model. Taken together, our findings reveal that Mkt1 plays a crucial role in sexual reproduction and virulence in C. neoformans.
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spelling pubmed-68115032019-11-03 Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans Son, Ye-Eun Fu, Ci Jung, Won-Hee Oh, Sang-Hun Kwak, Jin-Hwan Cardenas, Maria E. Heitman, Joseph Park, Hee-Soo Front Cell Infect Microbiol Cellular and Infection Microbiology The Mkt1–Pbp1 complex promotes mating-type switching by regulating the translation of HO mRNA in Saccharomyces cerevisiae. Here, we performed in vivo immunoprecipitation assays and mass spectrometry analyses in the human fungal pathogen Cryptococcus neoformans to show that Pbp1, a poly(A)-binding protein-binding protein, interacts with Mkt1 containing a PIN like-domain. Association of Pbp1 with Mkt1 was confirmed by co-immunoprecipitation assays. Results of spot dilution growth assays showed that unlike pbp1 deletion mutant strains, mkt1 deletion mutant strains were not resistant to heat stress compared with wild-type. However, similar to the pbp1 deletion mutant strains, the mkt1 deletion mutants exhibited both, defective dikaryotic hyphal production and reduced pheromone gene (MFα1) expression during mating. In addition, deletion of mkt1 caused attenuated virulence in a murine intranasal inhalation model. Taken together, our findings reveal that Mkt1 plays a crucial role in sexual reproduction and virulence in C. neoformans. Frontiers Media S.A. 2019-10-17 /pmc/articles/PMC6811503/ /pubmed/31681631 http://dx.doi.org/10.3389/fcimb.2019.00355 Text en Copyright © 2019 Son, Fu, Jung, Oh, Kwak, Cardenas, Heitman and Park. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Son, Ye-Eun
Fu, Ci
Jung, Won-Hee
Oh, Sang-Hun
Kwak, Jin-Hwan
Cardenas, Maria E.
Heitman, Joseph
Park, Hee-Soo
Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans
title Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans
title_full Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans
title_fullStr Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans
title_full_unstemmed Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans
title_short Pbp1-Interacting Protein Mkt1 Regulates Virulence and Sexual Reproduction in Cryptococcus neoformans
title_sort pbp1-interacting protein mkt1 regulates virulence and sexual reproduction in cryptococcus neoformans
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811503/
https://www.ncbi.nlm.nih.gov/pubmed/31681631
http://dx.doi.org/10.3389/fcimb.2019.00355
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