Nutritional Immunity and Fungal Pathogenesis

The human response to invading fungi includes a series of events that detect, kill, or clear the fungi. If the metabolic host response is unable to eliminate the fungi, an infection ensues. Some of the host response’s metabolic events to fungi can be imaged with molecules labelled with radionuclides. Several important clinical applications have been found with radiolabelled biomolecules of inflammation. 18F-fluorodeoxyglucose is the tracer that has been most widely investigated in the host defence of fungi. This tracer has added value in the early detection of infection, in staging and visualising dissemination of infection, and in monitoring antifungal treatment. Radiolabelled antimicrobial peptides showed promising results, but large prospective studies in fungal infection are lacking. Other tracers have also been used in imaging events of the host response, such as the migration of white blood cells at sites of infection, nutritional immunity in iron metabolism, and radiolabelled monoclonal antibodies. Many tracers are still at the preclinical stage. Some tracers require further studies before translation into clinical use. The application of therapeutic radionuclides offers a very promising clinical application of these tracers in managing drug-resistant fungi.

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Structural, Evolutionary, and Functional Analysis of the Protein O-Mannosyltransferase Family in Pathogenic Fungi

Journal of Fungi ◽

10.3390/jof7050328 ◽

2021 ◽

Vol 7 (5) ◽

pp. 328

Author(s):

María Dolores Pejenaute-Ochoa ◽

Carlos Santana-Molina ◽

Damien P. Devos ◽

José Ignacio Ibeas ◽

Alfonso Fernández-Álvarez

Keyword(s):

Functional Analysis ◽

Secretory Pathway ◽

Pathogenic Fungi ◽

Fungal Pathogenesis ◽

Post Translational Modification ◽

Key Factors ◽

Wide Range ◽

Single Deletion ◽

Asymmetrical Impact ◽

Substrate Proteins

Protein O-mannosyltransferases (Pmts) comprise a group of proteins that add mannoses to substrate proteins at the endoplasmic reticulum. This post-translational modification is important for the faithful transfer of nascent glycoproteins throughout the secretory pathway. Most fungi genomes encode three O-mannosyltransferases, usually named Pmt1, Pmt2, and Pmt4. In pathogenic fungi, Pmts, especially Pmt4, are key factors for virulence. Although the importance of Pmts for fungal pathogenesis is well established in a wide range of pathogens, questions remain regarding certain features of Pmts. For example, why does the single deletion of each pmt gene have an asymmetrical impact on host colonization? Here, we analyse the origin of Pmts in fungi and review the most important phenotypes associated with Pmt mutants in pathogenic fungi. Hence, we highlight the enormous relevance of these glycotransferases for fungal pathogenic development.

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Zinc and Sepsis

Nutrients ◽

10.3390/nu10080976 ◽

2018 ◽

Vol 10 (8) ◽

pp. 976 ◽

Cited By ~ 22

Author(s):

Wiebke Alker ◽

Hajo Haase

Keyword(s):

Defense Mechanism ◽

Acute Phase Proteins ◽

Innate Immune ◽

Zinc Homeostasis ◽

Major Health ◽

Nutritional Immunity ◽

Life Threatening ◽

Zinc Concentrations ◽

Severity Of The Disease ◽

Major Health Issue

Sepsis, defined as a “life-threatening organ dysfunction caused by a dysregulated host-response to infection” is a major health issue worldwide and still lacks a fully elucidated pathobiology and uniform diagnostic tests. The trace element zinc is known to be crucial to ensure an appropriate immune response. During sepsis a redistribution of zinc from serum into the liver has been observed and several studies imply a correlation between zinc and sepsis outcome. Therefore the alterations of zinc concentrations in different tissues might serve as one part of the host’s defense mechanism against pathogens during sepsis by diverse mechanisms. It has been suggested that zinc is involved in nutritional immunity, acts as a hepatoprotective agent, or a differentiation signal for innate immune cells, or supports the synthesis of acute phase proteins. Further knowledge about these events could help in the evaluation of how zinc could be optimally applied to improve treatment of septic patients. Moreover, the changes in zinc homeostasis are substantial and correlate with the severity of the disease, suggesting that zinc might also be useful as a diagnostic marker for evaluating the severity and predicting the outcome of sepsis.

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Molecular Genetic Approaches to the Study of Fungal Pathogenesis*

Annual Review of Phytopathology ◽

10.1146/annurev.py.27.090189.002335 ◽

1989 ◽

Vol 27 (1) ◽

pp. 463-481 ◽

Cited By ~ 23

Author(s):

S A Leong ◽

D W Holden

Keyword(s):

Molecular Genetic ◽

Fungal Pathogenesis

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Nutritional immunity: the impact of metals on lung immune cells and the airway microbiome during chronic respiratory disease

Respiratory Research ◽

10.1186/s12931-021-01722-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Claire Healy ◽

Natalia Munoz-Wolf ◽

Janné Strydom ◽

Lynne Faherty ◽

Niamh C. Williams ◽

...

Keyword(s):

Immune System ◽

Trace Metals ◽

Lung Disease ◽

Chronic Lung Disease ◽

Immune Cells ◽

Immune Cell ◽

Redox Activity ◽

Nutritional Immunity ◽

Airway Microbiome ◽

The Impact

AbstractNutritional immunity is the sequestration of bioavailable trace metals such as iron, zinc and copper by the host to limit pathogenicity by invading microorganisms. As one of the most conserved activities of the innate immune system, limiting the availability of free trace metals by cells of the immune system serves not only to conceal these vital nutrients from invading bacteria but also operates to tightly regulate host immune cell responses and function. In the setting of chronic lung disease, the regulation of trace metals by the host is often disrupted, leading to the altered availability of these nutrients to commensal and invading opportunistic pathogenic microbes. Similarly, alterations in the uptake, secretion, turnover and redox activity of these vitally important metals has significant repercussions for immune cell function including the response to and resolution of infection. This review will discuss the intricate role of nutritional immunity in host immune cells of the lung and how changes in this fundamental process as a result of chronic lung disease may alter the airway microbiome, disease progression and the response to infection.

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A Pathogenesis Assay Using Saccharomycescerevisiae and Caenorhabditiselegans Reveals Novel Roles for Yeast AP-1, Yap1, and Host Dual Oxidase BLI-3 in Fungal Pathogenesis

Eukaryotic Cell ◽

10.1128/ec.00367-08 ◽

2009 ◽

Vol 8 (8) ◽

pp. 1218-1227 ◽

Cited By ~ 39

Author(s):

Charu Jain ◽

Meijiang Yun ◽

Samuel M. Politz ◽

Reeta Prusty Rao

Keyword(s):

Fungal Infections ◽

Fungal Pathogenesis ◽

Host Responses ◽

Ros Production ◽

Oxygen Species ◽

Fungal Virulence ◽

Oxidase Gene ◽

Dual Oxidase ◽

Chemical Inhibition ◽

Yeast Mutants

ABSTRACT Treatment of systemic fungal infections is difficult because of the limited number of antimycotic drugs available. Thus, there is an immediate need for simple and innovative systems to assay the contribution of individual genes to fungal pathogenesis. We have developed a pathogenesis assay using Caenorhabditis elegans, an established model host, with Saccharomyces cerevisiae as the invading fungus. We have found that yeast infects nematodes, causing disease and death. Our data indicate that the host produces reactive oxygen species (ROS) in response to fungal infection. Yeast mutants sod1Δ and yap1Δ, which cannot withstand ROS, fail to cause disease, except in bli-3 worms, which carry a mutation in a dual oxidase gene. Chemical inhibition of the NADPH oxidase activity abolishes ROS production in worms exposed to yeast. This pathogenesis assay is useful for conducting systematic, whole-genome screens to identify fungal virulence factors as alternative targets for drug development and exploration of host responses to fungal infections.

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