Special Issue "Fungal Pathogens: Resistance and Novel Therapeutics"

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 11651

Special Issue Editors

Dr. Ryan Kean
E-Mail Website
Guest Editor
Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
Interests: Candida auris; polymicrobial infections; biofilms; decontamination; antifungal resistance
Dr. Leighann Sherry
E-Mail Website
Guest Editor
School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
Interests: fungi; Candida; novel antifungals; biofilms; resistance; chronic infection; oral

Special Issue Information

Dear Colleagues,

Fungal infections play a surprising yet unrecognised health burden on the global population, with diseases ranging from superficial infections to life-threatening bloodstream infections. Most pathogenic fungi are regarded as opportunistic, capable of causing debilitating disease in immunocompromised individuals and are commonly associated with unacceptability high mortality rates, accounting for ~1.6 million deaths each year. The success of fungal pathogenesis can be attributed to several factors, including the ability of these organisms to adapt to their environment and resist antifungal therapy. In a climate where antimicrobial resistance continues to increase and the rate of new drug discovery slows, coupled with the unprecedented emergence of new fungal pathogens such as Candida auris, it is of paramount interest to fully understand the underlying mechanisms of resistance and use these findings to translate and identify alternative strategies for the management of fungal infections.

This special issue welcomes original research and review articles and aims to collate the most recent findings on antifungal resistance and highlight potential novel therapeutics for the clinical management of these infections.

Dr. Ryan Kean
Dr. Leighann Sherry
Guest Editors

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. Antibiotics 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 2000 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

  • Pathogenic fungi
  • Candida
  • Aspergillus
  • Cryptococcus
  • novel agents
  • resistance
  • pathogenesis

Published Papers (5 papers)

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Research

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Article
Lactobacillus Plantarum 108 Inhibits Streptococcus mutans and Candida albicans Mixed-Species Biofilm Formation
Antibiotics 2020, 9(8), 478; https://doi.org/10.3390/antibiotics9080478 - 04 Aug 2020
Cited by 12 | Viewed by 1921
Abstract
Streptococcus mutans is the principal biofilm forming oral pathogen associated with dental caries. Studies have shown that Candida albicans, a commensal oral fungus is capable of forming pathogenic mixed-species biofilms with S. mutans. The treatment of bacterial and fungal infections using conventional [...] Read more.
Streptococcus mutans is the principal biofilm forming oral pathogen associated with dental caries. Studies have shown that Candida albicans, a commensal oral fungus is capable of forming pathogenic mixed-species biofilms with S. mutans. The treatment of bacterial and fungal infections using conventional antimicrobial agents has become challenging due to the antimicrobial resistance of the biofilm mode of growth. The present study aimed to evaluate the efficacy of secretory components of Lactobacillus plantarum 108, a potentially promising probiotic strain, against S. mutans and C. albicans single and mixed-species biofilms. L. plantarum 108 supernatant inhibited S. mutans and C. albicans single-species biofilms as shown by XTT reduction assay, crystal violet assay, and colony forming units counting. The probiotic supernatant significantly inhibited the S. mutans and C. albicans mixed-species biofilm formation. The pre-formed mixed-species biofilms were also successfully reduced. Confocal microscopy showed poorly developed biofilm architecture in the probiotic supernatant treated biofilms. Moreover, the expression of S. mutans genes associated with glucosyltransferase activity and C. albicans hyphal specific genes (HWP1, ALS1 and ALS3) were down-regulated in the presence of the probiotic supernatant. Altogether, the data demonstrated the capacity of L. plantarum 108 supernatant to inhibit the S. mutans and C. albicans mixed-species biofilms. Herein, we provide a new insight on the potential of probiotic-based strategies to prevent bacterial-fungal mixed-species biofilms associated with dental caries. Full article
(This article belongs to the Special Issue Fungal Pathogens: Resistance and Novel Therapeutics)
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Article
Bismuth Nanoantibiotics Display Anticandidal Activity and Disrupt the Biofilm and Cell Morphology of the Emergent Pathogenic Yeast Candida auris
Antibiotics 2020, 9(8), 461; https://doi.org/10.3390/antibiotics9080461 - 29 Jul 2020
Cited by 7 | Viewed by 1635
Abstract
Candida auris is an emergent multidrug-resistant pathogenic yeast, which forms biofilms resistant to antifungals, sanitizing procedures, and harsh environmental conditions. Antimicrobial nanomaterials represent an alternative to reduce the spread of pathogens—including yeasts—regardless of their drug-resistant profile. Here we have assessed the antimicrobial activity [...] Read more.
Candida auris is an emergent multidrug-resistant pathogenic yeast, which forms biofilms resistant to antifungals, sanitizing procedures, and harsh environmental conditions. Antimicrobial nanomaterials represent an alternative to reduce the spread of pathogens—including yeasts—regardless of their drug-resistant profile. Here we have assessed the antimicrobial activity of easy-to-synthesize bismuth nanoparticles (BiNPs) against the emergent multidrug-resistant yeast Candida auris, under both planktonic and biofilm growing conditions. Additionally, we have examined the effect of these BiNPs on cell morphology and biofilm structure. Under planktonic conditions, BiNPs MIC values ranged from 1 to 4 µg mL−1 against multiple C. auris strains tested, including representatives of all different clades. Regarding the inhibition of biofilm formation, the calculated BiNPs IC50 values ranged from 5.1 to 113.1 µg mL−1. Scanning electron microscopy (SEM) observations indicated that BiNPs disrupted the C. auris cell morphology and the structure of the biofilms. In conclusion, BiNPs displayed strong antifungal activity against all strains of C. auris under planktonic conditions, but moderate activity against biofilm growth. BiNPs may potentially contribute to reducing the spread of C. auris strains at healthcare facilities, as sanitizers and future potential treatments. More research on the antimicrobial activity of BiNPs is warranted. Full article
(This article belongs to the Special Issue Fungal Pathogens: Resistance and Novel Therapeutics)
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Communication
Synthesis and Identification of Pentathiepin-Based Inhibitors of Sporothrix brasiliensis
Antibiotics 2019, 8(4), 249; https://doi.org/10.3390/antibiotics8040249 - 03 Dec 2019
Cited by 3 | Viewed by 1967
Abstract
Sporothrix brasiliensis is the causative agent of zoonotic sporotrichosis in Brazil and is currently referred to as the most virulent species among those of clinical importance within the genus. Sporotrichosis is an emergent disease that has come to the forefront over two decades [...] Read more.
Sporothrix brasiliensis is the causative agent of zoonotic sporotrichosis in Brazil and is currently referred to as the most virulent species among those of clinical importance within the genus. Sporotrichosis is an emergent disease that has come to the forefront over two decades with a recent hot spot of sporotrichosis infection emerging in the state of Rio de Janeiro. The source of these infections is now at epidemic proportions with more than 4000 cases reported in Rio de Janeiro, Brazil, alone since 1998. We developed a focused library of a rare pentathiepin ring system and identified a potent substitution pattern that yielded compounds 21 and 22. These compounds were more potent than itraconazole which is the current standard of care for sporotrichosis. Full article
(This article belongs to the Special Issue Fungal Pathogens: Resistance and Novel Therapeutics)
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Article
Candida albicans Biofilm Heterogeneity and Tolerance of Clinical Isolates: Implications for Secondary Endodontic Infections
Antibiotics 2019, 8(4), 204; https://doi.org/10.3390/antibiotics8040204 - 30 Oct 2019
Cited by 12 | Viewed by 2493
Abstract
Aim: Endodontic infections are caused by the invasion of various microorganisms into the root canal system. Candida albicans is a biofilm forming yeast and the most prevalent eukaryotic microorganism in endodontic infections. In this study we investigated the ability of C. albicans to [...] Read more.
Aim: Endodontic infections are caused by the invasion of various microorganisms into the root canal system. Candida albicans is a biofilm forming yeast and the most prevalent eukaryotic microorganism in endodontic infections. In this study we investigated the ability of C. albicans to tolerate treatment with standard endodontic irrigants NaOCl (sodium hypochlorite), ethylenediaminetetraacetic acid (EDTA) and a combination thereof. We hypothesized that biofilm formed from a panel of clinical isolates differentially tolerate disinfectant regimens, and this may have implications for secondary endodontic infections. Methodology: Mature C. albicans biofilms were formed from 30 laboratory and oral clinical isolates and treated with either 3% NaOCl, 17% EDTA or a sequential treatment of 3% NaOCl followed by 17% EDTA for 5 min. Biofilms were then washed, media replenished and cells reincubated for an additional 24, 48 and 72 h at 37 °C. Regrowth was quantified using metabolic reduction, electrical impedance, biofilm biomass and microscopy at 0, 24, 48 and 72 h. Results: Microscopic analysis and viability readings revealed a significant initial killing effect by NaOCl, followed by a time dependent significant regrowth of C. albicans, but with inter-strain variability. In contrast to NaOCl, there was a continuous reduction in viability after EDTA treatment. Moreover, EDTA significantly inhibited regrowth after NaOCl treatment, though viable cells were still observed. Conclusions: Our results indicate that different C. albicans biofilm phenotypes grown in a non-complex surface topography have the potential to differentially tolerate standard endodontic irrigation protocols. This is the first study to report a strain dependent impact on efficacy of endodontic irrigants. Its suggested that within the complex topography of the root canal, a more difficult antimicrobial challenge, that existing endodontic irrigant regimens permit cells to regrow and drive secondary infections. Full article
(This article belongs to the Special Issue Fungal Pathogens: Resistance and Novel Therapeutics)
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Review

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Review
Current Antimycotics, New Prospects, and Future Approaches to Antifungal Therapy
Antibiotics 2020, 9(8), 445; https://doi.org/10.3390/antibiotics9080445 - 25 Jul 2020
Cited by 33 | Viewed by 3160
Abstract
Fungal infections represent an increasing threat to a growing number of immune- and medically compromised patients. Fungi are eukaryotic organisms and, as such, there is a limited number of selective targets that can be exploited for antifungal drug development. This has also resulted [...] Read more.
Fungal infections represent an increasing threat to a growing number of immune- and medically compromised patients. Fungi are eukaryotic organisms and, as such, there is a limited number of selective targets that can be exploited for antifungal drug development. This has also resulted in a very restricted number of antifungal drugs that are clinically available for the treatment of invasive fungal infections at the present time—polyenes, azoles, echinocandins, and flucytosine. Moreover, the utility of available antifungals is limited by toxicity, drug interactions and the emergence of resistance, which contribute to high morbidity and mortality rates. This review will present a brief summary on the landscape of current antifungals and those at different stages of clinical development. We will also briefly touch upon potential new targets and opportunities for novel antifungal strategies to combat the threat of fungal infections. Full article
(This article belongs to the Special Issue Fungal Pathogens: Resistance and Novel Therapeutics)
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