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Interplay between Antifungal Resistance and Virulence: Potential Novel Targets and...
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Interplay between Antifungal Resistance and Virulence: Potential Novel Targets and Therapeutic Strategies

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 17664

Special Issue Editor

Prof. Dr. Arianna Tavanti

E-Mail Website
Guest Editor
Department of Biology, University of Pisa, Via San Zeno 35-39, 56127 Pisa, Italy
Interests: Candida parapsilosis; Candida orthopsilosis; Candida metapsilosis; adhesion molecules; antifungal drug resistance; molecular mechanisms of fungal pathogenesis; gene editing

Special Issue Information

Dear Colleagues,

A complex interplay exists between antifungal resistance and virulence expressed by pathogenic fungi. Antifungal drugs currently on the market are limited, if compared to antibacterials, due to selective toxicity, costs, difficulties in therapeutic administration, and ineffectiveness, posing a serious challenge for clinicians. In addition, the widespread use of first-line common antifungals has led to a rise in the isolation frequency of drug resistance strains. The appearance of multi-drug resistant fungal species such as Candida auris has further complicated this scenario, highlighting a concerning need for new compound and target discovery. Comparative genomic studies have indicated several new potential antifungal targets which are currently under scrutiny. Among those, factors involved in virulence and pathogensis could provide new insights for the development of novel antifungal compounds.

This issue focuses on antifungal drug resistance mechanisms in clinically relevant fungal species as well as potential new targets and innovative therapeutic strategies to control fungal infections.

Prof. Dr. Arianna Tavanti
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

  • antifungal resistance
  • molecular mechanisms
  • antimicrobial peptides
  • virulence factors
  • antifungal compounds
  • antivirulence compounds

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Published Papers (4 papers)

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Research

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12 pages, 1940 KiB  
Article
In Silico Predicted Antifungal Peptides: In Vitro and In Vivo Anti-Candida Activity
by Tecla Ciociola, Walter Magliani, Tiziano De Simone, Thelma A. Pertinhez, Stefania Conti, Giorgio Cozza, Oriano Marin and Laura Giovati
J. Fungi 2021, 7(6), 439; https://doi.org/10.3390/jof7060439 - 31 May 2021
Cited by 6 | Viewed by 3277
Abstract
It has been previously demonstrated that synthetic antibody-derived peptides could exert a significant activity in vitro, ex vivo, and/or in vivo against microorganisms and viruses, as well as immunomodulatory effects through the activation of immune cells. Based on the sequence of previously described [...] Read more.
It has been previously demonstrated that synthetic antibody-derived peptides could exert a significant activity in vitro, ex vivo, and/or in vivo against microorganisms and viruses, as well as immunomodulatory effects through the activation of immune cells. Based on the sequence of previously described antibody-derived peptides with recognized antifungal activity, an in silico analysis was conducted to identify novel antifungal candidates. The present study analyzed the candidacidal and structural properties of in silico designed peptides (ISDPs) derived by amino acid substitutions of the parent peptide KKVTMTCSAS. ISDPs proved to be more active in vitro than the parent peptide and all proved to be therapeutic in Galleria mellonella candidal infection, without showing toxic effects on mammalian cells. ISDPs were studied by circular dichroism spectroscopy, demonstrating different structural organization. These results allowed to validate a consensus sequence for the parent peptide KKVTMTCSAS that may be useful in the development of novel antimicrobial molecules. Full article
(This article belongs to the Special Issue Interplay between Antifungal Resistance and Virulence: Potential Novel Targets and Therapeutic Strategies)
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11 pages, 979 KiB  
Article
Hmg1 Gene Mutation Prevalence in Triazole-Resistant Aspergillus fumigatus Clinical Isolates
by Agustin Resendiz-Sharpe, Margriet W.J. Hokken, Toine Mercier, Rita Merckx, Kamiel Verhagen, Lisa Dewitte, Willem J.G. Melchers, Paul E. Verweij, Johan Maertens and Katrien Lagrou
J. Fungi 2020, 6(4), 227; https://doi.org/10.3390/jof6040227 - 16 Oct 2020
Cited by 14 | Viewed by 3774
Abstract
Recently, mutations in the 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase-encoding gene (hmg1), a gene involved in ergosterol production, were associated with triazole-resistance in Aspergillus fumigatus. In this study, we determined the prevalence and characteristics of hmg1 mutations in a collection of clinical triazole-resistant A. [...] Read more.
Recently, mutations in the 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase-encoding gene (hmg1), a gene involved in ergosterol production, were associated with triazole-resistance in Aspergillus fumigatus. In this study, we determined the prevalence and characteristics of hmg1 mutations in a collection of clinical triazole-resistant A. fumigatus isolates collected during 2001–2019 from two international mycology reference centers: the Belgian National Reference Center for Mycosis and the Center of Expertise in Mycology Radboudumc/CWZ. Clinical isolates with and without cyp51A gene mutations and randomly selected wild-type (WT) controls were included. Isolates were characterized by in vitro susceptibility testing, cyp51A and hmg1 sequencing, and short tandem repeat typing. Available clinical records were analyzed for previous triazole exposure. In 23 isolates (24%) of the 95 triazole-resistant A. fumigatus isolates, hmg1 gene mutations were observed; including 5/23 (22%) isolates without cyp51A gene mutations and 18/72 (25%) with cyp51A mutations. Four previously described hmg1 gene mutations (E105K, G307R/D, G466V, and S541G) and two novel mutations (W273S and L304P) were found; 4/23 (17%) in the sterol-sensing-domain region. No triazole-antifungal exposure was reported in 75% (9/12) of patients harboring an isolate with hmg1 gene mutations. Three of 39 WT isolates (8%) contained a hmg1 gene mutation; E105K (2-isolates) and S541G. Hmg1 gene mutations were predominantly found in A. fumigatus with cyp51A mutations with voriconazole MICs ≥ 8 mg/L. Full article
(This article belongs to the Special Issue Interplay between Antifungal Resistance and Virulence: Potential Novel Targets and Therapeutic Strategies)
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Review

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24 pages, 1437 KiB  
Review
Genetic Manipulation as a Tool to Unravel Candida parapsilosis Species Complex Virulence and Drug Resistance: State of the Art
by Marina Zoppo, Noemi Poma, Mariagrazia Di Luca, Daria Bottai and Arianna Tavanti
J. Fungi 2021, 7(6), 459; https://doi.org/10.3390/jof7060459 - 7 Jun 2021
Cited by 8 | Viewed by 3415
Abstract
An increase in the rate of isolation of Candida parapsilosis in the past decade, as well as increased identification of azole-resistant strains are concerning, and require better understanding of virulence-like factors and drug-resistant traits of these species. In this regard, the present review [...] Read more.
An increase in the rate of isolation of Candida parapsilosis in the past decade, as well as increased identification of azole-resistant strains are concerning, and require better understanding of virulence-like factors and drug-resistant traits of these species. In this regard, the present review “draws a line” on the information acquired, thus far, on virulence determinants and molecular mechanisms of antifungal resistance in these opportunistic pathogens, mainly derived from genetic manipulation studies. This will provide better focus on where we stand in our understanding of the C. parapsilosis species complex–host interaction, and how far we are from defining potential novel targets or therapeutic strategies—key factors to pave the way for a more tailored management of fungal infections caused by these fungal pathogens. Full article
(This article belongs to the Special Issue Interplay between Antifungal Resistance and Virulence: Potential Novel Targets and Therapeutic Strategies)
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19 pages, 3244 KiB  
Review
Bioactive Compounds from Mangrove Endophytic Fungus and Their Uses for Microorganism Control
by Rafael Dorighello Cadamuro, Isabela Maria Agustini da Silveira Bastos, Izabella Thais Silva, Ariadne Cristiane Cabral da Cruz, Diogo Robl, Louis Pergaud Sandjo, Sergio Alves, Jr., Jose M. Lorenzo, David Rodríguez-Lázaro, Helen Treichel, Mário Steindel and Gislaine Fongaro
J. Fungi 2021, 7(6), 455; https://doi.org/10.3390/jof7060455 - 7 Jun 2021
Cited by 55 | Viewed by 6167
Abstract
Mangroves are ecosystems with unique characteristics due to the high salinity and amount of organic matter that house a rich biodiversity. Fungi have aroused much interest as they are an important natural source for the discovery of new bioactive compounds, with potential biotechnological [...] Read more.
Mangroves are ecosystems with unique characteristics due to the high salinity and amount of organic matter that house a rich biodiversity. Fungi have aroused much interest as they are an important natural source for the discovery of new bioactive compounds, with potential biotechnological and pharmacological interest. This review aims to highlight endophytic fungi isolated from mangrove plant species and the isolated bioactive compounds and their bioactivity against protozoa, bacteria and pathogenic viruses. Knowledge about this type of ecosystem is of great relevance for its preservation and as a source of new molecules for the control of pathogens that may be of importance for human, animal and environmental health. Full article
(This article belongs to the Special Issue Interplay between Antifungal Resistance and Virulence: Potential Novel Targets and Therapeutic Strategies)
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