A forkhead transcription factor contributes to the regulatory differences of pathogenicity in closely related fungal pathogens  

作　　者：Weixin Ke Yuyan Xie Yue Hu Hao Ding Xin Fan Jingjing Huang Xiuyun Tian Baokun Zhang Yingchun Xu Xiao Liu Ying Yang Linqi Wang 

机构地区：[1]State Key Laboratory of Mycology,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China [2]College of Life Sciences,University of Chinese Academy of Sciences,Beijing,China [3]Department of Infectious Diseases and Clinical Microbiology,Beijing Chaoyang Hospital,Capital Medical University,Beijing,China [4]Department of Clinical Laboratory,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing,China [5]Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing,China [6]Graduate School,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing,China [7]Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Disease,Department of Biotechnology,Beijing Institute of Radiation Medicine,Beijing,China

出　　处：《mLife》2022年第1期79-91,共13页微生物（英文）

基　　金：supported by the National Key Research and Development Program of China(2021YFC2300400)[Linqi Wang],2021YFC230000[Linqi Wang],2021YFA0911300[Xiao Liu],2021YFC2100600[Xiuyun Tian]:Major Infections Diseases Such as AIDS and Viral Hepatitis Prevention and Control Technology Major Projects(2018ZX10101003[Ying Yang]);and CAS Interdisciplinary Innovation Team(Linqi Wang).

摘　　要：Cryptococcus neoformans and its sister species Cryptococcus deuterogattii are important human fungal pathogens.Despite their phylogenetically close relationship,these two Cryptococcus pathogens are greatly different in their clinical characteristics.However,the determinants underlying the regulatory differences of their pathogenicity remain largely unknown.Here,we show that the forkhead transcription factor Hcm1 promotes infection in C.neoformans but not in C.deuterogattii.Monitoring in vitro and in vivo fitness outcomes of multiple clinical isolates from the two pathogens indicates that Hcm1 mediates pathogenicity in C.neoformans through its key involvement in oxidative stress defense.By comparison,Hcm1 is not critical for antioxidation in C.deuterogattii.Furthermore,we identified SRX1,which encodes the antioxidant sulfiredoxin,as a conserved target of Hcm1 in two Cryptococcus pathogens.Like HCM1,SRX1 had a greater role in antioxidation in C.neoformans than in C.deuterogattii.Significantly,overexpression of SRX1 can largely rescue the defective pathogenicity caused by the absence of Hcm1 in C.neoformans.Conversely,Srx1 is dispensable for virulence in C.deuterogattii.Overall,our findings demonstrate that the difference in the contribution of the antioxidant sulfiredoxin to oxidative stress defense underlies the Hcm1-mediated regulatory differences of pathogenicity in two closely related pathogens.

关 键 词：Cryptococcus deuterogattii Cryptococcus neoformans forkhead transcription factor PATHOGENICITY 

分 类 号：R519[医药卫生—内科学]