AUTHOR=Son Ye-Eun , Fu Ci , Jung Won-Hee , Oh Sang-Hun , Kwak Jin-Hwan , Cardenas Maria E. , Heitman Joseph , Park Hee-Soo 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2019.00355

DOI=10.3389/fcimb.2019.00355

ISSN=2235-2988

ABSTRACT=<p>The Mkt1–Pbp1 complex promotes mating-type switching by regulating the translation of <italic>HO</italic> mRNA in <italic>Saccharomyces cerevisiae</italic>. Here, we performed <italic>in vivo</italic> immunoprecipitation assays and mass spectrometry analyses in the human fungal pathogen <italic>Cryptococcus neoformans</italic> 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 <italic>pbp1</italic> deletion mutant strains, <italic>mkt1</italic> deletion mutant strains were not resistant to heat stress compared with wild-type. However, similar to the <italic>pbp1</italic> deletion mutant strains, the <italic>mkt1</italic> deletion mutants exhibited both, defective dikaryotic hyphal production and reduced pheromone gene (<italic>MF</italic>α1) expression during mating. In addition, deletion of <italic>mkt1</italic> 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 <italic>C. neoformans</italic>.</p>