scholarly journals Role of Protein Glycosylation in Interactions of Medically Relevant Fungi with the Host

2021 ◽  
Vol 7 (10) ◽  
pp. 875
Author(s):  
Manuela Gómez-Gaviria ◽  
Ana P. Vargas-Macías ◽  
Laura C. García-Carnero ◽  
Iván Martínez-Duncker ◽  
Héctor M. Mora-Montes
Keyword(s):  
Protein Trafficking ◽  
Mammalian Cells ◽  
Fungal Infections ◽  
Fungal Species ◽  
Protein Glycosylation ◽  
Amino Acid Side Chain ◽  
Post Translational Modification ◽  
Fungal Cell ◽  
The Relationship

Protein glycosylation is a highly conserved post-translational modification among organisms. It plays fundamental roles in many biological processes, ranging from protein trafficking and cell adhesion to host–pathogen interactions. According to the amino acid side chain atoms to which glycans are linked, protein glycosylation can be divided into two major categories: N-glycosylation and O-glycosylation. However, there are other types of modifications such as the addition of GPI to the C-terminal end of the protein. Besides the importance of glycoproteins in biological functions, they are a major component of the fungal cell wall and plasma membrane and contribute to pathogenicity, virulence, and recognition by the host immunity. Given that this structure is absent in host mammalian cells, it stands as an attractive target for developing selective compounds for the treatment of fungal infections. This review focuses on describing the relationship between protein glycosylation and the host–immune interaction in medically relevant fungal species.

scholarly journals Protein Glycosylation inAspergillus fumigatusIs Essential for Cell Wall Synthesis and Serves as a Promising Model of Multicellular Eukaryotic Development

2012 ◽  
Vol 2012 ◽  
pp. 1-21 ◽  
Author(s):  
Cheng Jin
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Posttranslational Modification ◽  
Mammalian Cells ◽  
Protein Glycosylation ◽  
Cell Wall Synthesis ◽  
Fungal Cell ◽  
Multiple Functions ◽  
Significant Attention

Glycosylation is a conserved posttranslational modification that is found in all eukaryotes, which helps generate proteins with multiple functions. Our knowledge of glycosylation mainly comes from the investigation of the yeastSaccharomyces cerevisiaeand mammalian cells. However, during the last decade, glycosylation in the human pathogenic moldAspergillus fumigatushas drawn significant attention. It has been revealed that glycosylation inA. fumigatusis crucial for its growth, cell wall synthesis, and development and that the process is more complicated than that found in the budding yeastS. cerevisiae. The present paper implies that the investigation of glycosylation inA. fumigatusis not only vital for elucidating the mechanism of fungal cell wall synthesis, which will benefit the design of new antifungal therapies, but also helps to understand the role of protein glycosylation in the development of multicellular eukaryotes. This paper describes the advances in functional analysis of protein glycosylation inA. fumigatus.

scholarly journals A Glucan Synthase FKS1 Homolog inCryptococcus neoformans Is Single Copy and Encodes an Essential Function

1999 ◽  
Vol 181 (2) ◽  
pp. 444-453 ◽  
Author(s):  
John R. Thompson ◽  
Cameron M. Douglas ◽  
Weili Li ◽  
Chong K. Jue ◽  
Barnali Pramanik ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mammalian Cells ◽  
Fungal Infections ◽  
Single Copy ◽  
Fungal Species ◽  
Term Treatment ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Long Term Treatment

ABSTRACT Cryptococcal meningitis is a fungal infection, caused byCryptococcus neoformans, which is prevalent in immunocompromised patient populations. Treatment failures of this disease are emerging in the clinic, usually associated with long-term treatment with existing antifungal agents. The fungal cell wall is an attractive target for drug therapy because the syntheses of cell wall glucan and chitin are processes that are absent in mammalian cells. Echinocandins comprise a class of lipopeptide compounds known to inhibit 1,3-β-glucan synthesis, and at least two compounds belonging to this class are currently in clinical trials as therapy for life-threatening fungal infections. Studies ofSaccharomyces cerevisiae and Candida albicansmutants identify the membrane-spanning subunit of glucan synthase, encoded by the FKS genes, as the molecular target of echinocandins. In vitro, the echinocandins show potent antifungal activity against Candida and Aspergillusspecies but are much less potent against C. neoformans. In order to examine why C. neoformans cells are less susceptible to echinocandin treatment, we have cloned a homolog of S. cerevisiae FKS1 from C. neoformans. We have developed a generalized method to evaluate the essentiality of genes inCryptococcus and applied it to the FKS1 gene. The method relies on homologous integrative transformation with a plasmid that can integrate in two orientations, only one of which will disrupt the target gene function. The results of this analysis suggest that the C. neoformans FKS1 gene is essential for viability. The C. neoformans FKS1 sequence is closely related to the FKS1 sequences from other fungal species and appears to be single copy in C. neoformans. Furthermore, amino acid residues known to be critical for echinocandin susceptibility in Saccharomyces are conserved in theC. neoformans FKS1 sequence.

scholarly journals Autophagy and LAP in the Fight against Fungal Infections: Regulation and Therapeutics

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Vasileios Oikonomou ◽  
Giorgia Renga ◽  
Antonella De Luca ◽  
Monica Borghi ◽  
Marilena Pariano ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Cell Types ◽  
Fungal Species ◽  
Host Immune Responses ◽  
Host Protection ◽  
Pathogen Clearance ◽  
The Relationship ◽  
Broad Role

Phagocytes fight fungi using canonical and noncanonical, also called LC3-associated phagocytosis (LAP), autophagy pathways. However, the outcomes of autophagy/LAP in shaping host immune responses appear to greatly vary depending on fungal species and cell types. By allowing efficient pathogen clearance and/or degradation of inflammatory mediators, autophagy proteins play a broad role in cellular and immune homeostasis during fungal infections. Indeed, defects in autophagic machinery have been linked with aberrant host defense and inflammatory states. Thus, understanding the molecular mechanisms underlying the relationship between the different forms of autophagy may offer a way to identify drugable molecular signatures discriminating between selective recognition of cargo and host protection. In this regard, IFN-γ and anakinra are teaching examples of successful antifungal agents that target the autophagy machinery. This article provides an overview of the role of autophagy/LAP in response to fungi and in their infections, regulation, and therapeutic exploitation.

scholarly journals The Role of Fungi in the Cocoa Production Chain and the Challenge of Climate Change

2021 ◽  
Vol 7 (3) ◽  
pp. 202
Author(s):  
Johannes Delgado-Ospina ◽  
Junior Bernardo Molina-Hernández ◽  
Clemencia Chaves-López ◽  
Gianfranco Romanazzi ◽  
Antonello Paparella
Keyword(s):  
Climate Change ◽  
Fungal Infections ◽  
Close Association ◽  
Pathogenic Fungi ◽  
Fungal Species ◽  
Mitigation Strategies ◽  
Plant Diseases ◽  
Production Chain ◽  
Cocoa Production

Background: The role of fungi in cocoa crops is mainly associated with plant diseases and contamination of harvest with unwanted metabolites such as mycotoxins that can reach the final consumer. However, in recent years there has been interest in discovering other existing interactions in the environment that may be beneficial, such as antagonism, commensalism, and the production of specific enzymes, among others. Scope and approach: This review summarizes the different fungi species involved in cocoa production and the cocoa supply chain. In particular, it examines the presence of fungal species during cultivation, harvest, fermentation, drying, and storage, emphasizing the factors that possibly influence their prevalence in the different stages of production and the health risks associated with the production of mycotoxins in the light of recent literature. Key findings and conclusion: Fungi associated with the cocoa production chain have many different roles. They have evolved in a varied range of ecosystems in close association with plants and various habitats, affecting nearly all the cocoa chain steps. Reports of the isolation of 60 genera of fungi were found, of which only 19 were involved in several stages. Although endophytic fungi can help control some diseases caused by pathogenic fungi, climate change, with increased rain and temperatures, together with intensified exchanges, can favour most of these fungal infections, and the presence of highly aggressive new fungal genotypes increasing the concern of mycotoxin production. For this reason, mitigation strategies need to be determined to prevent the spread of disease-causing fungi and preserve beneficial ones.

scholarly journals Overview on the Prevalence of Fungal Infections, Immune Response, and Microbiome Role in COVID-19 Patients

2021 ◽  
Vol 7 (9) ◽  
pp. 720
Author(s):  
Maryam Roudbary ◽  
Sunil Kumar ◽  
Awanish Kumar ◽  
Lucia Černáková ◽  
Fatemeh Nikoomanesh ◽  
...  
Keyword(s):  
Immune Response ◽  
Intensive Care ◽  
Intensive Care Units ◽  
Fungal Infections ◽  
Fungal Species ◽  
Fungal Diseases ◽  
Severe Illness ◽  
Rising Incidence ◽  
Cryptococcus Spp

Patients with severe COVID-19, such as individuals in intensive care units (ICU), are exceptionally susceptible to bacterial and fungal infections. The most prevalent fungal infections are aspergillosis and candidemia. Nonetheless, other fungal species (for instance, Histoplasma spp., Rhizopus spp., Mucor spp., Cryptococcus spp.) have recently been increasingly linked to opportunistic fungal diseases in COVID-19 patients. These fungal co-infections are described with rising incidence, severe illness, and death that is associated with host immune response. Awareness of the high risks of the occurrence of fungal co-infections is crucial to downgrade any arrear in diagnosis and treatment to support the prevention of severe illness and death directly related to these infections. This review analyses the fungal infections, treatments, outcome, and immune response, considering the possible role of the microbiome in these patients. The search was performed in Medline (PubMed), using the words “fungal infections COVID-19”, between 2020–2021.

scholarly journals The Chitin Connection

mBio ◽  
2012 ◽  
Vol 3 (2) ◽  
Author(s):  
David L. Goldman ◽  
Alfin G. Vicencio
Keyword(s):  
Cell Wall ◽  
Cell Membrane ◽  
Fungal Infections ◽  
Allergic Inflammation ◽  
Chitinase Activity ◽  
Chitin Deacetylase ◽  
Fungal Cell ◽  
Content Type ◽  
Covalently Linked

ABSTRACTChitin, a polymer ofN-acetylglucosamine, is an essential component of the fungal cell wall. Chitosan, a deacetylated form of chitin, is also important in maintaining cell wall integrity and is essential forCryptococcus neoformansvirulence. In their article, Gilbert et al. [N. M. Gilbert, L. G. Baker, C. A. Specht, and J. K. Lodge, mBio 3(1):e00007-12, 2012] demonstrate that the enzyme responsible for chitosan synthesis, chitin deacetylase (CDA), is differentially attached to the cell membrane and wall. Bioactivity is localized to the cell membrane, where it is covalently linked via a glycosylphosphatidylinositol (GPI) anchor. Findings from this study significantly enhance our understanding of cryptococcal cell wall biology. Besides the role of chitin in supporting structural stability, chitin and host enzymes with chitinase activity have an important role in host defense and modifying the inflammatory response. Thus, chitin appears to provide a link between the fungus and host that involves both innate and adaptive immune responses. Recently, there has been increased attention to the role of chitinases in the pathogenesis of allergic inflammation, especially asthma. We review these findings and explore the possible connection between fungal infections, the induction of chitinases, and asthma.

scholarly journals Antifungal Treatment Aggravates Sepsis through the Elimination of Intestinal Fungi

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Baifa Sheng ◽  
Yihui Chen ◽  
Lihua Sun ◽  
Peng Xu ◽  
Ben Han ◽  
...  
Keyword(s):  
Antifungal Therapy ◽  
Protective Role ◽  
Fungal Cell ◽  
Distal Small Intestine ◽  
Gram Positive Bacteria ◽  
Health And Disease ◽  
Mouse Intestine ◽  
Critical Patients ◽  
The Relationship

Prophylactic antifungal therapy is widely adopted clinically for critical patients and effective in reducing the morbidity of invasive fungal infection and improves outcomes of those diagnosed patients; however, it is not associated with higher overall survival. As intestinal commensal fungi play a fundamental role in the host immune response in health and disease, we propose that antifungal therapy may eliminate intestinal fungi and aggravate another critical syndrome, sepsis. Here, with murine sepsis model, we found that antifungal therapy with fluconazole dismissed intestinal fungal burden and aggravated endotoxin-induced but no gram-positive bacteria-induced sepsis. Nevertheless, antifungal therapy did not exert its detrimental effect on germ-free mice. Moreover, colonizing more commensal fungi in the mouse intestine or administration of fungal cell wall component mannan protected the mice from endotoxin-induced sepsis. On the molecular level, we demonstrated that antifungal therapy aggravated endotoxin sepsis through promoting Gasdermin D cleavage in the distal small intestine. Intestinal colonization with commensal fungi inhibited Gasdermin D cleavage in response to lipopolysaccharide challenge. These findings show that intestinal fungi inhibit Gasdermin D-mediated pyroptosis and protect the mice from endotoxin-induced sepsis. This study demonstrates the protective role of intestinal fungi in the pathogenesis of endotoxin-induced sepsis in the laboratory. It will undoubtedly prompt us to study the relationship between antifungal therapy and sepsis in critical patients who are susceptible to endotoxin-induced sepsis in the future.

scholarly journals Protein glycosylation is essential for SARS-CoV-2 infection

2021 ◽  
Author(s):  
Aitor Casas-Sanchez ◽  
Alessandra Romero-Ramirez ◽  
Eleanor Hargreaves ◽  
Edward I Patterson ◽  
Grant L Hughes ◽  
...  
Keyword(s):  
Host Cell ◽  
Protein Conformation ◽  
Protein Glycosylation ◽  
Post Translational Modification ◽  
Cell Infection ◽  
Normal Functioning ◽  
Viral Particles ◽  
Show Evidence ◽  
Glycosylation Pathway

AbstractSARS-CoV-2 extensively N-glycosylates its surface spike (S) proteins. This post-translational modification is essential to modulate protein conformation and host cell invasion. Each S monomer can be modified with up to 22 N-glycans. To meet the high demand of protein glycosylation during virus replication, SARS-CoV-2 upregulates the expression of host N-glycosylation genes. Although a substantial amount of detail is known about the structure of S protein N-glycans, the role of N-glycosylation in SARS-CoV-2 infection remains largely undetermined. Here, we investigated the essentiality of the host N-glycosylation pathway and viral N-glycans for SARS-CoV-2 infection. When either monkey or human cells were preincubated with glycosylation inhibitors, including FDA-approved iminosugars, virus infection was significantly reduced. This infection phenotype was confirmed after RNAi knockdown of several glycosylation genes. In addition, enzymatic deglycosylation of whole viral particles confirmed that accessible oligosaccharides on the SARS-CoV-2 surface are essential for host cell infection. Altogether, we show evidence that the normal functioning of the host N- glycosylation machinery is essential not only for SARS-CoV-2 to infect, but also to produce new functional virions. These findings open the door for developing new approaches targeting N-glycosylation against COVID-19.

scholarly journals Protein Glycosylation Investigated by Mass Spectrometry: An Overview

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1986
Author(s):  
Anna Illiano ◽  
Gabriella Pinto ◽  
Chiara Melchiorre ◽  
Andrea Carpentieri ◽  
Vincenza Faraco ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Trafficking ◽  
Inflammatory Diseases ◽  
Protein Glycosylation ◽  
Qualitative And Quantitative Analysis ◽  
Post Translational Modification ◽  
Cellular Mechanisms ◽  
Disease States ◽  
Recognition Protein ◽  
The Individual

The protein glycosylation is a post-translational modification of crucial importance for its involvement in molecular recognition, protein trafficking, regulation, and inflammation. Indeed, abnormalities in protein glycosylation are correlated with several disease states such as cancer, inflammatory diseases, and congenial disorders. The understanding of cellular mechanisms through the elucidation of glycan composition encourages researchers to find analytical solutions for their detection. Actually, the multiplicity and diversity of glycan structures bond to the proteins, the variations in polarity of the individual saccharide residues, and the poor ionization efficiencies make their detection much trickier than other kinds of biopolymers. An overview of the most prominent techniques based on mass spectrometry (MS) for protein glycosylation (glycoproteomics) studies is here presented. The tricks and pre-treatments of samples are discussed as a crucial step prodromal to the MS analysis to improve the glycan ionization efficiency. Therefore, the different instrumental MS mode is also explored for the qualitative and quantitative analysis of glycopeptides and the glycans structural composition, thus contributing to the elucidation of biological mechanisms.

scholarly journals Antiviral Role of IFITM Proteins in Classical Swine Fever Virus Infection

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 126 ◽  
Author(s):  
Cheng Li ◽  
Hongqing Zheng ◽  
Yifan Wang ◽  
Wang Dong ◽  
Yaru Liu ◽  
...  
Keyword(s):  
Classical Swine Fever Virus ◽  
Mammalian Cells ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Late Endosomes ◽  
Early Endosomes ◽  
Infected Cells ◽  
The Relationship ◽  
Antiviral Role

The proteins IFITM1, IFITM2, and IFITM3 are host effectors against a broad range of RNA viruses whose roles in classical swine fever virus (CSFV) infection had not yet been reported. We investigated the effect of these proteins on CSFV replication in mammalian cells. The proteins were overexpressed and silenced using lentiviruses. Confocal microscopy was used to determine the distribution of these proteins in the cells, and immunofluorescence colocalization analysis was used to evaluate the relationship between IFITMs and the CSFV endosomal pathway, including early endosomes, late endosomes, and lysosomes. IFITM1, IFITM2, or IFITM3 overexpression significantly inhibited CSFV replication, whereas protein knockdown enhanced CSFV replication. In porcine alveolar macrophages (PAMs), IFITM1 was mainly located at the cell surface, whereas IFITM2 and IFITM3 were mainly located in the cytoplasm. Following CSFV infection, the distribution of IFITM1 changed. IFITM1, IFITM2, and IFITM3 colocalization with Lamp1, IFITM2 with Rab5 and Rab7, and IFITM3 with Rab7 were observed in CSFV-infected cells. Collectively, these results provide insights into the possible mechanisms associated with the anti-CSFV action of the IFITM family.

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