Current opinions on autophagy in pathogenicity of fungi

Zhu, Xue-Ming; Li, Lin; Wu, Min; Liang, Shuang; Shi, Huanbin; Liu, Xiao-Hong; Lin, Fu‐Cheng

doi:10.1080/21505594.2018.1551011

Cited by 72 publications

(62 citation statements)

References 64 publications

(87 reference statements)

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“…Due to the fact that C. neoformans causes infections mainly in immunodeficient individuals [55], affecting up to 223,000 individuals per year [56] and that there is a constraint regarding treatment; it is necessary to broad the knowledge on this fungus biology in order to search for alternatives for treatment and disease control. Understanding the molecular mechanisms that connect both pathogenicity and autophagy could provide us new insights into the relationship established during the fungal infection [57]. One of the central steps of the autophagy pathway is the autophagosome formation in which, in yeast model S. cerevisiae, Atg4 is important to start the autophagosome synthesis by processing Atg8 [58].…”

Section: Discussionmentioning

confidence: 99%

Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans

et al. 2020

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Autophagy is a mechanism responsible for intracellular degradation and recycling of macromolecules and organelles, essential for cell survival in adverse conditions. More than 40 autophagy-related (ATG) genes have been identified and characterized in fungi, among them ATG4 and ATG8. ATG4 encodes a cysteine protease (Atg4) that plays an important role in autophagy by initially processing Atg8 at its C-terminus region. Atg8 is a ubiquitin-like protein essential for the synthesis of the double-layer membrane that constitutes the autophagosome vesicle, responsible for delivering the cargo from the cytoplasm to the vacuole lumen. The contributions of Atg-related proteins in the pathogenic yeast in the genus Cryptococcus remain to be explored, to elucidate the molecular basis of the autophagy pathway. In this context, we aimed to investigate the role of autophagy-related proteins 4 and 8 (Atg4 and Atg8) during autophagy induction and their contribution with non-autophagic events in C. neoformans. We found that Atg4 and Atg8 are conserved proteins and that they interact physically with each other. ATG gene deletions resulted in cells sensitive to nitrogen starvation. ATG4 gene disruption affects Atg8 degradation and its translocation to the vacuole lumen, after autophagy induction. Both atg4 and atg8 mutants are more resistant to oxidative stress, have an impaired growth in the presence of the cell wall-perturbing agent Congo Red, and are sensitive to the proteasome inhibitor bortezomib (BTZ). By that, we conclude that in C. neoformans the autophagy-related proteins Atg4 and Atg8 play an important role in the autophagy pathway; which are required for autophagy regulation, maintenance of amino acid levels and cell adaptation to stressful conditions. OPEN ACCESS Citation: Roberto TN, Lima RF, Pascon RC, Idnurm A, Vallim MA (2020) Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans. PLoS ONE 15(4): e0230981. https://doi.org/10.Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files.individuals [2]. The therapy against cryptococcosis requires a long period of treatment with antifungal drugs used singly or in combination, some of which are highly toxic to the patient [3]. Due to the long period of clinical treatment, some reports indicate that fungi of the genus Cryptococcus may have a high potential to antifungal resistance, which could explain the therapeutic failures and recurrent relapses in the patients with cryptococcosis [4]. Thus, further studies for new strategies that contribute with the knowledge about the treatment of this mycosis, leading to the deficiency of growth, multiplication, and/or survival of the fungus in the host are of great importance. In this context, the elucidation of autophagic pathways in fungi may provide new insights into the relationship established during the infection process between pathogen and host [5].Autophagy is an intracellular mechanism responsible for degradation and recycling of macr...

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Section: Discussionmentioning

confidence: 99%

Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans

et al. 2020

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“…Based upon proteomics, is has been suggested that selective ribosome autophagy might occur in Candida orthopsilosis biofilms (Pires et al, 2016), but our study might be the first to directly demonstrate activation of autophagy within a fungal biofilm. In addition, autophagy has been shown to be activated within filamentous fungal plant pathogens as they encounter nutrient poor conditions during the infection process (Kershaw and Talbot, 2009;Zhu et al, 2019) and autophagy is required for fungal plant pathogenesis (Zhu et al, 2019). It will be interesting to investigate what microenvironmental changes might be responsible for activation of autophagy (Corona Velazquez and Jackson, 2018) but, as discussed further below, it is possible that reactive oxygen species (ROS) could be involved.…”

Section: Subcellular Modifications During Biofilm Developmentmentioning

confidence: 99%

Aspergillus nidulans biofilm formation modifies cellular architecture and enables light-activated autophagy

Lingo

Shukla

Osmani

et al. 2021

MBoC

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After growing on surfaces, including those of medical and industrial importance, fungal biofilms self-generate internal microenvironments. We previously reported that gaseous microenvironments around founder Aspergillus nidulans cells change during biofilm formation causing microtubules (MTs) to disassemble under control of the hypoxic transcription factor SrbA. Here we investigate if biofilm formation might also promote changes to structures involved in exocytosis and endocytosis. During biofilm formation the ER remained intact but ER exit sites and the Golgi apparatus were modified as were endocytic actin patches. The biofilm driven changes required the SrbA hypoxic transcription factor and could be triggered by nitric oxide, further implicating gaseous regulation of biofilm cellular architecture. By tracking GFP-Atg8 dynamics, biofilm founder cells were also observed to undergo autophagy. Most notably, biofilm cells that had undergone autophagy were triggered into further autophagy by spinning disc confocal light. Our findings indicate that fungal biofilm formation modifies the secretory and endocytic apparatus and show biofilm cells can also undergo autophagy that is reactivated by light. The findings provide new insights into the changes occurring in fungal biofilm cell biology that potentially impact their unique characteristics, including antifungal drug resistance. [Media: see text]

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“…Autophagy is involved in many important processes, including cell differentiation, development, and responses to nutrient starvation. The disruption of autophagy leads to impaired pathogenesis in some plant fungal pathogens (Sumita et al 2017;Shi et al 2019;Ren et al 2018;Nadal and Gold 2010;Josefsen et al 2012;Deng et al 2009;Liu et al 2016;Zhu et al 2019).…”

Section: Introductionmentioning

confidence: 99%

UvAtg8-Mediated Autophagy Regulates Fungal Growth, Stress Responses, Conidiation, and Pathogenesis in Ustilaginoidea virens

Meng

Xiong

Jagernath

et al. 2020

Rice

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Background: Ustilaginoidea virens has become one of the most devastating rice pathogens in China, as well as other rice-growing areas. Autophagy is an important process in normal cell differentiation and development among various organisms. To date, there has been no optimized experimental system introduced for the study of autophagy in U. virens. In addition, the function of autophagy in pathogenesis remains unknown in U. virens. Therefore, the functional analyses of UvAtg8 may potentially shed some light on the regulatory mechanism and function of autophagy in U. virens. Results: In this study, we characterized the functions of UvAtg8, which is a homolog of Saccharomyces cerevisiae ScAtg8, in the rice false smut fungus U. virens. The results showed that UvATG8 is essential for autophagy in U. virens. Also, the GFP-UvATG8 strain, which could serve as an appropriate marker for monitoring autophagy in U. virens, was generated. Furthermore, this study found that the ΔUvatg8 mutant was defective in the vegetative growth, conidiation, adaption to oxidative, hyperosmotic, cell wall stresses, and production of toxic compounds. Pathogenicity assays indicated that deletion of UvATG8 resulted in significant reduction in virulence of U. virens. Further microscopic examinations of the infection processes revealed that the severe virulence defects in the ΔUvatg8 were mainly caused by the highly reduced conidiation and secondary spore formation. Conclusions: Our results indicated that the UvAtg8 is necessary for the fungal growth, stresses responses, conidiation, secondary spore formation, and pathogenicity of U. virens. Moreover, our research finding will potentially assist in further clarifying the molecular mechanism of U. virens infection, as well as provide a good marker for autophagy in U. virens and a good reference value for the further development of effective fungicides based on gene targeting.

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Current opinions on autophagy in pathogenicity of fungi

Cited by 72 publications

References 64 publications

Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans

Biological functions of the autophagy-related proteins Atg4 and Atg8 in Cryptococcus neoformans

Aspergillus nidulans biofilm formation modifies cellular architecture and enables light-activated autophagy

UvAtg8-Mediated Autophagy Regulates Fungal Growth, Stress Responses, Conidiation, and Pathogenesis in Ustilaginoidea virens

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