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Pathogenesis and Treatment of Candida Species
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Pathogenesis and Treatment of Candida Species

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 (15 April 2023) | Viewed by 10606

Special Issue Editor

Dr. Shankar Thangamani

E-Mail Website
Guest Editor
College of Veterinary Medicine, Purdue University, 625 Harrison St, West Lafayette, IN 47906, USA
Interests: fungal pathogenesis; drug discovery; microbiome; bacterial-fungal interactions

Special Issue Information

Dear Colleague,

Fungal pathogens mainly cause severe infections in immunocompromised patients. Importantly, the recent emergence of a novel multi-drug-resistant Candida auris which predominately colonizes in the skin complicates the existing issue. The most common antifungal drugs used to treat Candida infections are limited to three main classes: azoles, polyenes and echinocandins. The treatment of disseminated Candidiasis is further complicated by drug toxicity associated with high doses of these antifungal agents and the increasing resistance to these drugs acquired by Candida strains.

This Special Issue on “Pathogenesis and Treatment of Candida Species” will concentrate on describing the various aspects of this emerging novel pathogen. The focus of this Special Issue will be placed on studies related to antifungal resistance, drug discovery, microbial and host factors regulating the colonization and pathogenesis, as well as animal models pertaining to Candida auris.

Dr. Shankar Thangamani
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

  • Candida auris
  • antifungal resistance
  • skin colonization
  • animal models
  • drug discovery

Published Papers (5 papers)

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12 pages, 1048 KiB  
Article
Evaluation of a Novel FKS1 R1354H Mutation Associated with Caspofungin Resistance in Candida auris Using the CRISPR-Cas9 System
by Maiko Kiyohara, Taiga Miyazaki, Michiyo Okamoto, Tatsuro Hirayama, Koichi Makimura, Hiroji Chibana, Nana Nakada, Yuya Ito, Makoto Sumiyoshi, Nobuyuki Ashizawa, Kazuaki Takeda, Naoki Iwanaga, Takahiro Takazono, Koichi Izumikawa, Katsunori Yanagihara, Shigeru Kohno and Hiroshi Mukae
J. Fungi 2023, 9(5), 529; https://0-doi-org.brum.beds.ac.uk/10.3390/jof9050529 - 29 Apr 2023
Cited by 4 | Viewed by 1656
Abstract
Outbreaks of invasive infections, with high mortality rates, caused by multidrug-resistant Candida auris have been reported worldwide. Although hotspot mutations in FKS1 are an established cause of echinocandin resistance, the actual contribution of these mutations to echinocandin resistance remains unknown. Here, we sequenced [...] Read more.
Outbreaks of invasive infections, with high mortality rates, caused by multidrug-resistant Candida auris have been reported worldwide. Although hotspot mutations in FKS1 are an established cause of echinocandin resistance, the actual contribution of these mutations to echinocandin resistance remains unknown. Here, we sequenced the FKS1 gene of a caspofungin-resistant clinical isolate (clade I) and identified a novel resistance mutation (G4061A inducing R1354H). We applied the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system to generate a recovered strain (H1354R) in which only this single nucleotide mutation was reverted to its wild-type sequence. We also generated mutant strains with only the R1354H mutation introduced into C. auris wild-type strains (clade I and II) and analyzed their antifungal susceptibility. Compared to their parental strains, the R1354H mutants exhibited a 4- to 16-fold increase in caspofungin minimum inhibitory concentration (MIC) while the H1354R reverted strain exhibited a 4-fold decrease in caspofungin MIC. In a mouse model of disseminated candidiasis, the in vivo therapeutic effect of caspofungin was more closely related to the FKS1 R1354H mutation and the virulence of the strain than its in vitro MIC. The CRISPR-Cas9 system could thus aid in elucidating the mechanism underlying drug resistance in C. auris. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Candida Species)
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17 pages, 4357 KiB  
Article
2,4-Diacetylphloroglucinol Modulates Candida albicans Virulence
by Artyom A. Stepanov, Darya V. Poshvina and Alexey S. Vasilchenko
J. Fungi 2022, 8(10), 1018; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8101018 - 27 Sep 2022
Cited by 6 | Viewed by 1731
Abstract
The dimorphic fungus Candida albicans is one of the most important opportunistic pathogens for humankind. The use of fungicides against Candida could be associated with sub-inhibitory effects, which are referred to as fungal stress responses and are undesirable for the host. In this [...] Read more.
The dimorphic fungus Candida albicans is one of the most important opportunistic pathogens for humankind. The use of fungicides against Candida could be associated with sub-inhibitory effects, which are referred to as fungal stress responses and are undesirable for the host. In this work, we investigated the antifungal action of 2,4-diacetylphloroglucinol (2,4-DAPG) against Candida albicans ATCC 10231 with a focus on their biofilm-forming ability. We found that 2,4-DAPG was able to reduce the ability of Candida cells to form biofilms, but complete inhibition and eradication effects were not achieved. Furthermore, C. albicans cells in the adherent state were characterized by reduced susceptibility to 2,4-DAPG compared to planktonic cells. The investigation of the mechanisms that could explain the antibiofilm action of 2,4-DAPG revealed a reduction in the cell`s surface hydrophobicity and the inhibition of the yeast-to-hyphae transition. The inhibition of the Candida cells filamentation was accompanied by an increase in the expression of the NRG1 gene, which is a negative regulator of hyphal development. In addition, we microscopically visualized the treated biofilms and revealed numerous channels that were decorated with particles and localized on the hyphae. We assumed that these hyphal structures could be associated with the secretion of aspartyl proteases (Sap). The performed assessments revealed an increase in the activity of Sap, which was accompanied by an increase in the expression of the sap2 and sap4 genes. The antifungal action of 2,4-DAPG is known to be associated with affecting the permeability of cellular structures, which leads to H+ATPase malfunction and the disruption of mitochondrial respiration. The subsequent cytosol acidification and generation of ROS trigger the inhibition of Candida filamentation and activation of Sap production. The introduction of antioxidant Trolox simultaneously with 2,4-DAPG leads to a reduction in Sap production. Collectively, the obtained data indicate new aspects of the interaction of fungal cells with 2,4-DAPG, an antimicrobial metabolite of Pseudomonas spp. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Candida Species)
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20 pages, 8407 KiB  
Article
Silver Nanoparticles Prepared Using Encephalartos laurentianus De Wild Leaf Extract Have Inhibitory Activity against Candida albicans Clinical Isolates
by Fatemah A. Alherz, Walaa A. Negm, Engy Elekhnawy, Thanaa A. El-Masry, Eman M. Haggag, Moneerah J. Alqahtani and Ismail A. Hussein
J. Fungi 2022, 8(10), 1005; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8101005 - 25 Sep 2022
Cited by 14 | Viewed by 1608
Abstract
Candida albicans is a major human opportunistic pathogen causing infections, which range from cutaneous to invasive systemic infections. Herein, the antifungal and anti-biofilm potential of silver nanoparticles (AgNPs) green synthesized in the presence of Encephalartos laurentianus leaf extract (ELLE) were investigated. The bioactive [...] Read more.
Candida albicans is a major human opportunistic pathogen causing infections, which range from cutaneous to invasive systemic infections. Herein, the antifungal and anti-biofilm potential of silver nanoparticles (AgNPs) green synthesized in the presence of Encephalartos laurentianus leaf extract (ELLE) were investigated. The bioactive chemicals of ELLE, including phenolics, flavonoids, and glycosides were identified and quantified for the first time. AgNPs showed minimum inhibitory concentration (MIC) values against C. albicans clinical isolates ranging from 8 to 256 µg/mL. In addition, AgNPs significantly decreased biofilm formation. The impact of AgNPs on the expression of the genes encoding biofilm formation was assessed using qRT-PCR. AgNPs had a beneficial role in the macroscopic wound healing, and they resulted in complete epithelization without any granulation tissue or inflammation. Treatment with AgNPs resulted in negative immunostaining of tumor necrosis factor-α. The levels of the inflammation markers, interleukin-6 and interleukin-1β, significantly decreased (p < 0.05) in the AgNPs-treated group. There was also a pronounced increase in the gene expression of fibronectin and platelet-derived growth factor in the wound tissues. Thus, AgNPs synthesized using ELLE may be a promising antifungal and wound healing agent. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Candida Species)
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9 pages, 1778 KiB  
Article
Silver Nanoparticles: A Promising Antifungal Agent against the Growth and Biofilm Formation of the Emergent Candida auris
by Reem AlJindan and Doaa M. AlEraky
J. Fungi 2022, 8(7), 744; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8070744 - 19 Jul 2022
Cited by 17 | Viewed by 2479
Abstract
Candida auris is a globally-emerging pathogen that is correlated to nosocomial infections and high mortality rates, causing major outbreaks in hospitals and serious public health concerns worldwide. This study investigated the antifungal activity of silver nanoparticles (AgNPs) on clinical isolates of C. auris. [...] Read more.
Candida auris is a globally-emerging pathogen that is correlated to nosocomial infections and high mortality rates, causing major outbreaks in hospitals and serious public health concerns worldwide. This study investigated the antifungal activity of silver nanoparticles (AgNPs) on clinical isolates of C. auris. A total of eight clinical isolates were collected from blood, urine, ear swab, and groin. C. auris was confirmed by MALDI-TOF MS, and gene sequencing. All isolates confirmed as C. auris were subjected to antimicrobial agents, including amphotericin B, fluconazole, caspofungin, voriconazole, micafungin, and flucytosine. A serial dilution of a silver nanoparticles solution was prepared to test antifungal susceptibility testing under planktonic conditions. Moreover, an antibiofilm activity assay was determined using a colony-forming assay and a cell viability assay by a live–dead yeast kit. Significant antifungal and antibiofilm activity of AgNPs was detected against all isolates; MIC was <6.25 μg/mL, the range of MFC was from 6.25 to 12.5 μg/mL for all isolates, and the highest value of IC50 was 3.2 μg/mL. Silver nanomaterials could represent a possible antimicrobial agent to prevent outbreaks caused by C. auris infections. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Candida Species)
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10 pages, 299 KiB  
Brief Report
The Mortality Attributable to Candidemia in C. auris Is Higher than That in Other Candida Species: Myth or Reality?
by Carlos A. Alvarez-Moreno, Soraya Morales-López, Gerson J. Rodriguez, Jose Y. Rodriguez, Estelle Robert, Carine Picot, Andrés Ceballos-Garzon, Claudia M. Parra-Giraldo and Patrice Le Pape
J. Fungi 2023, 9(4), 430; https://0-doi-org.brum.beds.ac.uk/10.3390/jof9040430 - 31 Mar 2023
Cited by 10 | Viewed by 2638
Abstract
Candida auris has become a major health threat due to its transmissibility, multidrug resistance and severe outcomes. In a case-control design, 74 hospitalised patients with candidemia were enrolled. In total, 22 cases (29.7%) and 52 controls (C. albicans, 21.6%; C. parapsilosis [...] Read more.
Candida auris has become a major health threat due to its transmissibility, multidrug resistance and severe outcomes. In a case-control design, 74 hospitalised patients with candidemia were enrolled. In total, 22 cases (29.7%) and 52 controls (C. albicans, 21.6%; C. parapsilosis, 21.6%; C. tropicalis, 21.6%; C. glabrata, 1.4%) were included and analysed in this study. Risk factors, clinical and microbiological characteristics and outcomes of patients with C. auris and non-auris Candida species (NACS) candidemia were compared. Previous fluconazole exposure was significantly higher in C. auris candidemia patients (OR 3.3; 1.15–9.5). Most C. auris isolates were resistant to fluconazole (86.3%) and amphotericin B (59%) whilst NACS isolates were generally susceptible. No isolates resistant to echinocandins were detected. The average time to start antifungal therapy was 3.6 days. Sixty-three (85.1%) patients received adequate antifungal therapy, without significant differences between the two groups. The crude mortality at 30 and 90 days of candidemia was up to 37.8% and 40.5%, respectively. However, there was no difference in mortality both at 30 and 90 days between the group with candidemia by C. auris (31.8%) and by NACS (42.3%) (OR 0.6; 95% IC 0.24–1.97) and 36.4% and 42.3% (0.77; 0.27–2.1), respectively. In this study, mortality due to candidemia between C. auris and NACS was similar. Appropriate antifungal therapy in both groups may have contributed to finding no differences in outcomes. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Candida Species)
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