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Fungal-Unique Pathways and Their Utilization for the Development of Novel...
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Fungal-Unique Pathways and Their Utilization for the Development of Novel Antifungals

A special issue of Journal of Fungi (ISSN 2309-608X).

Deadline for manuscript submissions: closed (30 November 2018)

Special Issue Editor

Prof. Nir Osherov

E-Mail Website
Guest Editor
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
Interests: Aspergillus fumigatus virulence factors; development of antifungal drugs

Special Issue Information

Dear Colleagues,

Fungal infections are estimated to affect over a quarter of the world’s population. Life-threatening fungal infections are on the rise, resulting in at least 1.5 million deaths per year worldwide. Because fungi are eukaryotes, the development of new antifungals has been slow. Many antifungals have serious side effects and resistance is rapidly developing. Most new antifungals are simply a variation on an existing theme.

Papers in this Special Issue focus on the development of novel antifungals targeting biochemical pathways unique to fungi. Bioinformatic analyses and metabolic networking coupled with transcriptome data have reconstructed the major fungal metabolic pathways and identified numerous unique or highly conserved targets for antifungal drug development. A growing number of these targets has been validated by gene deletion and virulence analysis in model organisms. Several compounds inhibiting key metabolic processes have been described. Most excitingly, one compound F901318 that inhibits the fungal–specific enzyme dihydroorotate (DHODH/URA1) catalysing the fourth enzymatic step of pyrimidine biosynthesis, is currently in clinical trials, validating the promise of this approach.

I believe that systematic drug screening to identify and develop compounds inhibiting key fungal-unique metabolic enzymes, should now be seriously undertaken. Only a combined effort between academia and pharma will enable us to address the growing challenge of antifungal resistance and rising infection.

Prof. Nir Osherov
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Aspergillus fumigatus
  • antifungals
  • antifungal drugs
  • fungal–specific enzyme
  • fungal infections

Published Papers (3 papers)

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Review

28 pages, 1924 KiB  
Review
Identification of Antifungal Targets Based on Computer Modeling
by Elena Bencurova, Shishir K. Gupta, Edita Sarukhanyan and Thomas Dandekar
J. Fungi 2018, 4(3), 81; https://doi.org/10.3390/jof4030081 - 04 Jul 2018
Cited by 12 | Viewed by 5593
Abstract
Aspergillus fumigatus is a saprophytic, cosmopolitan fungus that attacks patients with a weak immune system. A rational solution against fungal infection aims to manipulate fungal metabolism or to block enzymes essential for Aspergillus survival. Here we discuss and compare different bioinformatics approaches to [...] Read more.
Aspergillus fumigatus is a saprophytic, cosmopolitan fungus that attacks patients with a weak immune system. A rational solution against fungal infection aims to manipulate fungal metabolism or to block enzymes essential for Aspergillus survival. Here we discuss and compare different bioinformatics approaches to analyze possible targeting strategies on fungal-unique pathways. For instance, phylogenetic analysis reveals fungal targets, while domain analysis allows us to spot minor differences in protein composition between the host and fungi. Moreover, protein networks between host and fungi can be systematically compared by looking at orthologs and exploiting information from host–pathogen interaction databases. Further data—such as knowledge of a three-dimensional structure, gene expression data, or information from calculated metabolic fluxes—refine the search and rapidly put a focus on the best targets for antimycotics. We analyzed several of the best targets for application to structure-based drug design. Finally, we discuss general advantages and limitations in identification of unique fungal pathways and protein targets when applying bioinformatics tools. Full article
(This article belongs to the Special Issue Fungal-Unique Pathways and Their Utilization for the Development of Novel Antifungals)
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14 pages, 1782 KiB  
Review
Vitamin Biosynthesis as an Antifungal Target
by Zohar Meir and Nir Osherov
J. Fungi 2018, 4(2), 72; https://doi.org/10.3390/jof4020072 - 17 Jun 2018
Cited by 41 | Viewed by 7412
Abstract
The large increase in the population of immunosuppressed patients, coupled with the limited efficacy of existing antifungals and rising resistance toward them, have dramatically highlighted the need to develop novel drugs for the treatment of invasive fungal infections. An attractive possibility is the [...] Read more.
The large increase in the population of immunosuppressed patients, coupled with the limited efficacy of existing antifungals and rising resistance toward them, have dramatically highlighted the need to develop novel drugs for the treatment of invasive fungal infections. An attractive possibility is the identification of possible drug targets within essential fungal metabolic pathways not shared with humans. Here, we review the vitamin biosynthetic pathways (vitamins A–E, K) as candidates for the development of antifungals. We present a set of ranking criteria that identify the vitamin B2 (riboflavin), B5 (pantothenic acid), and B9 (folate) biosynthesis pathways as being particularly rich in new antifungal targets. We propose that recent scientific advances in the fields of drug design and fungal genomics have developed sufficiently to merit a renewed look at these pathways as promising sources for the development of novel classes of antifungals. Full article
(This article belongs to the Special Issue Fungal-Unique Pathways and Their Utilization for the Development of Novel Antifungals)
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13 pages, 3927 KiB  
Review
Lipid Biosynthesis as an Antifungal Target
by Jiao Pan, Cuiting Hu and Jae-Hyuk Yu
J. Fungi 2018, 4(2), 50; https://doi.org/10.3390/jof4020050 - 20 Apr 2018
Cited by 55 | Viewed by 6161
Abstract
Lipids, commonly including phospholipids, sphingolipids, fatty acids, sterols, and triacylglycerols (TAGs), are important biomolecules for the viability of all cells. Phospholipids, sphingolipids, and sterols are important constituents of biological membranes. Many lipids play important roles in the regulation of cell metabolism by acting [...] Read more.
Lipids, commonly including phospholipids, sphingolipids, fatty acids, sterols, and triacylglycerols (TAGs), are important biomolecules for the viability of all cells. Phospholipids, sphingolipids, and sterols are important constituents of biological membranes. Many lipids play important roles in the regulation of cell metabolism by acting as signaling molecules. Neutral lipids, including TAGs and sterol esters (STEs), are important storage lipids in cells. In view of the importance of lipid molecules, this review briefly summarizes the metabolic pathways for sterols, phospholipids, sphingolipids, fatty acids, and neutral lipids in fungi and illustrates the differences between fungal and human (or other mammalian) cells, especially in relation to lipid biosynthetic pathways. These differences might provide valuable clues for us to find target proteins for novel antifungal drugs. In addition, the development of lipidomics technology in recent years has supplied us with a shortcut for finding new antifungal drug targets; this ability is important for guiding our research on pathogenic fungi. Full article
(This article belongs to the Special Issue Fungal-Unique Pathways and Their Utilization for the Development of Novel Antifungals)
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