Zinc Finger Proteins in the Human Fungal Pathogen Cryptococcus neoformans

Zinc is one of the essential trace elements in eukaryotes and it is a critical structural component of a large number of proteins. Zinc finger proteins (ZNFs) are zinc-finger domain-containing proteins stabilized by bound zinc ions and they form the most abundant proteins, serving extraordinarily diverse biological functions. In recent years, many ZNFs have been identified and characterized in the human fungal pathogen Cryptococcus neoformans, a fungal pathogen causing fatal meningitis mainly in immunocompromised individuals. It has been shown that ZNFs play important roles in the morphological development, differentiation, and virulence of C. neoformans. In this review, we, first, briefly introduce the ZNFs and their classification. Then, we explain the identification and classification of the ZNFs in C. neoformans. Next, we focus on the biological role of the ZNFs functionally characterized so far in the sexual reproduction, virulence factor production, ion homeostasis, pathogenesis, and stress resistance in C. neoformans. We also discuss the perspectives on future function studies of ZNFs in C. neoformans.

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A Predicted Mannoprotein Cmp1 Regulates Fungal Virulence in Cryptococcus neoformans

Pathogens ◽

10.3390/pathogens9110881 ◽

2020 ◽

Vol 9 (11) ◽

pp. 881

Author(s):

Lian-Tao Han ◽

Lei Wu ◽

Tong-Bao Liu

Keyword(s):

Cryptococcus Neoformans ◽

Fungal Pathogen ◽

Gene Expression Pattern ◽

Fungal Virulence ◽

Human Fungal Pathogen ◽

Overexpression Strain ◽

Reproduction Process ◽

Localization Analysis ◽

Survival Assay

The capsule of the fungal pathogen Cryptococcus neoformans consists of glucuronoxylomannan (GXM), glucuronoxylomannogalactan (GXMGal), and mannoproteins (MPs). MPs are a kind of glycoproteins with low content but high immunogenicity, which can stimulate the immune protection of the host. However, there is not much information about the role of mannoproteins in virulence of the human fungal pathogen C. neoformans. In this study, we reported the identification and functional analysis of a predicted mannoprotein Cmp1 that regulates fungal virulence in C. neoformans. Gene expression pattern analysis indicates that the CMP1 gene was ubiquitously expressed at all stages of cryptococcal development. Subcellular localization analysis indicated that Cmp1 was localized in the cytoplasm of cryptococcal cells. Disruption or overexpression of CMP1 results in impairing capsule formation in Cryptococcus, but it does not affect the melanin production and sensitivity under various stress conditions, nor does it affect the sexual reproduction process of Cryptococcus. Survival assay showed that the pathogenicity of the cmp1Δ mutant or the CMP1 overexpression strain was significantly attenuated in a murine inhalation model of cryptococcosis. In conclusion, our findings implied that the mannoprotein Cmp1 is required for the virulence of C. neoformans.

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Zinc Finger Proteins in Neuro-Related Diseases Progression

Frontiers in Neuroscience ◽

10.3389/fnins.2021.760567 ◽

2021 ◽

Vol 15 ◽

Author(s):

Siyuan Bu ◽

Yihan Lv ◽

Yusheng Liu ◽

Sen Qiao ◽

Hongmei Wang

Keyword(s):

Zinc Finger ◽

Neurological Diseases ◽

Zinc Finger Proteins ◽

Regulate Gene Expression ◽

Pathophysiological Role ◽

Zinc Finger Domains ◽

Eukaryotic Genomes ◽

Regulate Gene

Zinc finger proteins (ZNF) are among the most abundant proteins in eukaryotic genomes. It contains several zinc finger domains that can selectively bind to certain DNA or RNA and associate with proteins, therefore, ZNF can regulate gene expression at the transcriptional and translational levels. In terms of neurological diseases, numerous studies have shown that many ZNF are associated with neurological diseases. The purpose of this review is to summarize the types and roles of ZNF in neuropsychiatric disorders. We will describe the structure and classification of ZNF, then focus on the pathophysiological role of ZNF in neuro-related diseases and summarize the mechanism of action of ZNF in neuro-related diseases.

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Faculty Opinions recommendation of Systematic genetic analysis of virulence in the human fungal pathogen Cryptococcus neoformans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1123230.580516 ◽

2008 ◽

Author(s):

Guilhem Janbon

Keyword(s):

Genetic Analysis ◽

Cryptococcus Neoformans ◽

Fungal Pathogen ◽

Human Fungal Pathogen

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Erratum: Proprietary science, open science and the role of patent disclosure: the case of zinc-finger proteins

Nature Biotechnology ◽

10.1038/nbt0509-485d ◽

2009 ◽

Vol 27 (5) ◽

pp. 485-485

Author(s):

Subhashini Chandrasekharan ◽

Sapna Kumar ◽

Cory M Valley ◽

Arti Rai

Keyword(s):

Zinc Finger ◽

Zinc Finger Proteins ◽

Open Science

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Role of clathrin-mediated endocytosis in the use of heme and hemoglobin by the fungal pathogen Cryptococcus neoformans

Cellular Microbiology ◽

10.1111/cmi.12961 ◽

2018 ◽

Vol 21 (3) ◽

pp. e12961 ◽

Cited By ~ 5

Author(s):

Gaurav Bairwa ◽

Mélissa Caza ◽

Linda Horianopoulos ◽

Guanggan Hu ◽

James Kronstad

Keyword(s):

Cryptococcus Neoformans ◽

Fungal Pathogen

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Broadening the spectrum of fluorescent protein tools for use in the encapsulated human fungal pathogen Cryptococcus neoformans

Fungal Genetics and Biology ◽

10.1016/j.fgb.2020.103365 ◽

2020 ◽

Vol 138 ◽

pp. 103365

Author(s):

Garrick W.K. Spencer ◽

Sheena M.H. Chua ◽

Paige E. Erpf ◽

Maha S.I. Wizrah ◽

Taylor G. Dyba ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Fungal Pathogen ◽

Fluorescent Protein ◽

Human Fungal Pathogen

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Cryptococcus neoformans Evades Pulmonary Immunity by Modulating Xylose Precursor Transport

Infection and Immunity ◽

10.1128/iai.00288-20 ◽

2020 ◽

Vol 88 (8) ◽

Author(s):

Lucy X. Li ◽

Camaron R. Hole ◽

Javier Rangel-Moreno ◽

Shabaana A. Khader ◽

Tamara L. Doering

Keyword(s):

Cryptococcus Neoformans ◽

Mutant Strain ◽

Fungal Pathogen ◽

Wild Type ◽

Content Type ◽

Helper Cell Type ◽

Lymphoid Structures ◽

Type Infection

ABSTRACT Cryptococcus neoformans is a fungal pathogen that kills almost 200,000 people each year and is distinguished by abundant and unique surface glycan structures that are rich in xylose. A mutant strain of C. neoformans that cannot transport xylose precursors into the secretory compartment is severely attenuated in virulence in mice yet surprisingly is not cleared. We found that this strain failed to induce the nonprotective T helper cell type 2 (Th2) responses characteristic of wild-type infection, instead promoting sustained interleukin 12p40 (IL-12p40) induction and increased IL-17A (IL-17) production. It also stimulated dendritic cells to release high levels of proinflammatory cytokines, a behavior we linked to xylose expression. We further discovered that inducible bronchus-associated lymphoid tissue (iBALT) forms in response to infection with either wild-type cryptococci or the mutant strain with reduced surface xylose; although iBALT formation is slowed in the latter case, the tissue is better organized. Finally, our temporal studies suggest that lymphoid structures in the lung restrict the spread of mutant fungi for at least 18 weeks after infection, which is in contrast to ineffective control of the pathogen after infection with wild-type cells. These studies demonstrate the role of xylose in modulation of host response to a fungal pathogen and show that cryptococcal infection triggers iBALT formation.

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