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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.02690

Conserved autophagy pathway contributes to stress tolerance and virulence and differentially controls autophagic flux upon nutrient starvation in Cryptococcus neoformans

 Xueru Zhao1, Weijia Feng2, Xiangyang Zhu2,  Chenxi Li3, Xiaoyu Ma3, Xin Li2,  Xudong Zhu4* and  Dongsheng Wei1*
  • 1Department of Microbiology, College of Life Sciences, Nankai University, China
  • 2College of Life Sciences, Nankai University, China
  • 3College of Life Sciences, Beijing Normal University, China
  • 4Institute of Biochemistry and Molecular Biology, School of Life Sciences, Beijing Normal University, China

Cryptococcus neoformans is a major fungal pathogen primarily infecting immunocompromised hosts. Autophagy is mainly a catabolic process induced by and coping with nutrient deficiency and various stressful conditions. Human environment often imposes various stresses to C. neoformans and therefore, autophagic responsiveness of C. neoformans to these stresses often decides its survival in host. However, a systematic study on how these ATG genes influence these phenotypes in C. neoformans is still lacking. In this study, 22 ATG-deficient strains were constructed to investigate their roles in virulence, pathogenesis, stress response, starvation tolerance and autophagic flux in C.neoformans. We found several interesting points. 1 Atg6 and Atg14-03, have a significant impact on the ability of growth at 37℃ and laccase production. 2 Atg2∆ and atg6∆ strains were also sensitive to oxidative stress caused by H2O2. 3 About half of atg∆ strains displayed a higher sensitivity to 1.5 M NaCl and remarkable lower virulence than WT in Galleria mellonella model. 4 Autophagic flux was dependent on Atg1-Atg13 complex, Atg5-Atg12-Atg16 complex, Atg2-Atg18 complex and Atg11, GFP-Atg8 cleavage was hardly detected in these autophagy-defective mutants. 5 More interestingly, cleavage of GFP-Atg8 was still observed in atg3∆, atg4∆, atg6∆ and atg14∆ strains. 6 There is no obvious ATG10 homologs in this fungus. 7 These ATG genes contribute differentially to carbon and nitrogen starvation tolerance comparing with S. cerevisiae. This investigation provided very useful information about the specific roles played by ATG genes in Cryptococcus neoformans.

Keywords: Cryptococcus neoformans, Atg genes, Autophagy, Atg8, Starvation, Virulence, Stress Tolerance

Received: 08 Jul 2019; Accepted: 06 Nov 2019.

Copyright: © 2019 Zhao, Feng, Zhu, Li, Ma, Li, Zhu and Wei. 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.

* Correspondence:
Dr. Xudong Zhu, Institute of Biochemistry and Molecular Biology, School of Life Sciences, Beijing Normal University, Tianjin, China, zhu11187@bnu.edu.cn
Dr. Dongsheng Wei, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, China, weidongsheng@nankai.edu.cn