cryptococcus neoformans mediator protein ssn8 negatively regulates diverse physiological processes and is required for virulence新型隐球菌中介蛋白质ssn8负调节需要不同的生理过程和毒性.pdfVIP

Cryptococcus neoformans Mediator Protein Ssn8 Negatively Regulates Diverse Physiological Processes and Is Required for Virulence 1 1 1 2 1 Lin-Ing Wang , Yu-Sheng Lin , Kung-Hung Liu , Ambrose Y. Jong , Wei-Chiang Shen * 1 Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan, 2 Division of Hematology-Oncology, Childrens Hospital Los Angeles, Los Angeles, California, United States of America Abstract Cryptococcus neoformans is a ubiquitously distributed human pathogen. It is also a model system for studying fungal virulence, physiology and differentiation. Light is known to inhibit sexual development via the evolutionarily conserved white collar proteins in C. neoformans. To dissect molecular mechanisms regulating this process, we have identified the SSN8 gene whose mutation suppresses the light-dependent CWC1 overexpression phenotype. Characterization of sex- related phenotypes revealed that Ssn8 functions as a negative regulator in both heterothallic a-a mating and same-sex mating processes. In addition, Ssn8 is involved in the suppression of other physiological processes including invasive growth, and production of capsule and melanin. Interestingly, Ssn8 is also required for the maintenance of cell wall integrity and virulence. Our gene expression studies confirmed that deletion of SSN8 results in de-repression of genes involved in sexual development and melanization. Epistatic and yeast two hybrid studies suggest that C. neoformans Ssn8 plays critical roles downstream of the Cpk1 MAPK cascade and Ste12 and possibly resides at one of the major branches downstream of the Cwc complex in the light-mediated sexual development pathway