Special Issue "Candida albicans: A Major Fungal Pathogen of Humans"

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Fungal Pathogens".

Deadline for manuscript submissions: closed (30 September 2021).

Special Issue Editor

Dr. Jonathan Richardson
E-Mail Website
Guest Editor
Centre for Host-Microbiome Interactions, King’s College London, London SE1 1UL, UK
Interests: host-fungal interactions; fungal virulence factors and pathogenicity mechanisms
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Fungal diseases are a significant and growing challenge to healthcare that cause millions of life-threatening infections every year. Candida albicans is typically regarded as a commensal component of the human microbiota but frequently causes superficial infections in otherwise healthy individuals, and invasive life-threatening infections in those with compromised immunity. In 2017, the national cost of Candida-associated hospitalizations was estimated to be $1.4 billion in the USA alone [1]. C. albicans accounts for ~75% of all Candida infections, representing a serious medical challenge for worldwide communities, particularly in the ever-increasing immunocompromised patient population (e.g. chemotherapy, transplants, ICU).

Understanding the biology of C. albicans, how it interacts with the human host, and how it causes disease is of critical importance if we are to engage with and overcome the numerous challenges associated with effective treatment. In this Special Edition of Pathogens, "Candida albicans: a major fungal pathogen of humans" will present recent advances in our understanding of C. albicans in the context of host interaction, infection, and therapeutics.

Potential topics may include (but are not limited to):

  • Cell wall biology
  • Genomic plasticity and epigenetic diversity
  • Regulation of hypha development and contact sensing
  • Biofilms
  • Mucosal and systemic infection (and associated immune responses)
  • Acquisition of micronutrients
  • Therapeutics and diagnostics
  • Tolerance and resistance to antifungal drugs
  • Medical case reports

I look forward to your contributions to this valuable and thought-provoking Special Issue.

Reference

1. Benedict, K., Jackson, B. R., Chiller, T. & Beer, K. D. Estimation of Direct Healthcare Costs of Fungal Diseases in the United States. Clin Infect Dis 68, 1791–1797, doi:10.1093/cid/ciy776 (2019).

Dr. Jonathan Richardson
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 papers will be 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. Pathogens 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 1800 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 albicans
  • fungal infection
  • candidiasis
  • thrush
  • hyphae
  • innate
  • adaptive
  • mucosal
  • systemic
  • biofilm
  • antifungal

Published Papers (7 papers)

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Research

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Article
Sphingolipid Inhibitors as an Alternative to Treat Candidiasis Caused by Fluconazole-Resistant Strains
Pathogens 2021, 10(7), 856; https://doi.org/10.3390/pathogens10070856 - 07 Jul 2021
Viewed by 678
Abstract
Candida species are fungal pathogens known to cause a wide spectrum of diseases, and Candida albicans and Candida glabrata are the most common associated with invasive infections. A concerning aspect of invasive candidiasis is the emergence of resistant isolates, especially those highly resistant [...] Read more.
Candida species are fungal pathogens known to cause a wide spectrum of diseases, and Candida albicans and Candida glabrata are the most common associated with invasive infections. A concerning aspect of invasive candidiasis is the emergence of resistant isolates, especially those highly resistant to fluconazole, the first choice of treatment for these infections. Fungal sphingolipids have been considered a potential target for new therapeutic approaches and some inhibitors have already been tested against pathogenic fungi. The present study therefore aimed to evaluate the action of two sphingolipid synthesis inhibitors, aureobasidin A and myriocin, against different C. albicans and C. glabrata strains, including clinical isolates resistant to fluconazole. Susceptibility tests of aureobasidin A and myriocin were performed using CLSI protocols, and their interaction with fluconazole was evaluated by a checkerboard protocol. All Candida strains tested were sensitive to both inhibitors. Regarding the evaluation of drug interaction, both aureobasidin A and myriocin were synergic with fluconazole, demonstrating that sphingolipid synthesis inhibition could enhance the effect of fluconazole. Thus, these results suggest that sphingolipid inhibitors in conjunction with fluconazole could be useful for treating candidiasis cases, especially those caused by fluconazole resistant isolates. Full article
(This article belongs to the Special Issue Candida albicans: A Major Fungal Pathogen of Humans)
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Article
Metamorphic Protein Folding Encodes Multiple Anti-Candida Mechanisms in XCL1
Pathogens 2021, 10(6), 762; https://doi.org/10.3390/pathogens10060762 - 17 Jun 2021
Viewed by 636
Abstract
Candida species cause serious infections requiring prolonged and sometimes toxic therapy. Antimicrobial proteins, such as chemokines, hold great interest as potential additions to the small number of available antifungal drugs. Metamorphic proteins reversibly switch between multiple different folded structures. XCL1 is a metamorphic, [...] Read more.
Candida species cause serious infections requiring prolonged and sometimes toxic therapy. Antimicrobial proteins, such as chemokines, hold great interest as potential additions to the small number of available antifungal drugs. Metamorphic proteins reversibly switch between multiple different folded structures. XCL1 is a metamorphic, antimicrobial chemokine that interconverts between the conserved chemokine fold (an α–β monomer) and an alternate fold (an all-β dimer). Previous work has shown that human XCL1 kills C. albicans but has not assessed whether one or both XCL1 folds perform this activity. Here, we use structurally locked engineered XCL1 variants and Candida killing assays, adenylate kinase release assays, and propidium iodide uptake assays to demonstrate that both XCL1 folds kill Candida, but they do so via different mechanisms. Our results suggest that the alternate fold kills via membrane disruption, consistent with previous work, and the chemokine fold does not. XCL1 fold-switching thus provides a mechanism to regulate the XCL1 mode of antifungal killing, which could protect surrounding tissue from damage associated with fungal membrane disruption and could allow XCL1 to overcome candidal resistance by switching folds. This work provides inspiration for the future design of switchable, multifunctional antifungal therapeutics. Full article
(This article belongs to the Special Issue Candida albicans: A Major Fungal Pathogen of Humans)
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Article
The Synthesis and Evaluation of Multivalent Glycopeptoids as Inhibitors of the Adhesion of Candida albicans
Pathogens 2021, 10(5), 572; https://doi.org/10.3390/pathogens10050572 - 08 May 2021
Viewed by 718
Abstract
Multivalency is a strategy commonly used by medicinal carbohydrate chemists to increase the affinity of carbohydrate-based small molecules for their protein targets. Although this approach has been very successful in enhancing binding to isolated carbohydrate-binding proteins, anticipating the multivalent presentations that will improve [...] Read more.
Multivalency is a strategy commonly used by medicinal carbohydrate chemists to increase the affinity of carbohydrate-based small molecules for their protein targets. Although this approach has been very successful in enhancing binding to isolated carbohydrate-binding proteins, anticipating the multivalent presentations that will improve biological activity in cellular assays remains challenging. In this work we investigate linear molecular scaffolds for the synthesis of a low valency presentation of a divalent galactoside 1, previously identified by us as an inhibitor of the adhesion of opportunistic fungal pathogen Candida albicans to buccal epithelial cells (BECs). Adhesion inhibition assays revealed that multivalent glycoconjugate 3 is more effective at blocking C. albicans adherence to BECs upon initial exposure to epithelial cells. Interestingly, 3 did not seem to have any effect when it was pre-incubated with yeast cells, in contrast to the original lead compound 1, which caused a 25% reduction of adhesion. In competition assays, where yeast cells and BECs were co-incubated, multivalent glycoconjugate 3 inhibited up to 49% C. albicans adherence in a dose-dependent manner. The combined effect of compound 1 towards both yeast cells and BECs allowed it to achieve over 60% inhibition of the adhesion of C. albicans to BECs in competition assays. Full article
(This article belongs to the Special Issue Candida albicans: A Major Fungal Pathogen of Humans)
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Article
Fungicidal Activity of a Safe 1,3,4-Oxadiazole Derivative Against Candida albicans
Pathogens 2021, 10(3), 314; https://doi.org/10.3390/pathogens10030314 - 07 Mar 2021
Viewed by 627
Abstract
Candida albicans is the most common species isolated from nosocomial bloodstream infections. Due to limited therapeutic arsenal and increase of drug resistance, there is an urgent need for new antifungals. Therefore, the antifungal activity against C. albicans and in vivo toxicity of a [...] Read more.
Candida albicans is the most common species isolated from nosocomial bloodstream infections. Due to limited therapeutic arsenal and increase of drug resistance, there is an urgent need for new antifungals. Therefore, the antifungal activity against C. albicans and in vivo toxicity of a 1,3,4-oxadiazole compound (LMM6) was evaluated. This compound was selected by in silico approach based on chemical similarity. LMM6 was highly effective against several clinical C. albicans isolates, with minimum inhibitory concentration values ranging from 8 to 32 µg/mL. This compound also showed synergic effect with amphotericin B and caspofungin. In addition, quantitative assay showed that LMM6 exhibited a fungicidal profile and a promising anti-biofilm activity, pointing to its therapeutic potential. The evaluation of acute toxicity indicated that LMM6 is safe for preclinical trials. No mortality and no alterations in the investigated parameters were observed. In addition, no substantial alteration was found in Hippocratic screening, biochemical or hematological analyzes. LMM6 (5 mg/kg twice a day) was able to reduce both spleen and kidneys fungal burden and further, promoted the suppresses of inflammatory cytokines, resulting in infection control. These preclinical findings support future application of LMM6 as potential antifungal in the treatment of invasive candidiasis. Full article
(This article belongs to the Special Issue Candida albicans: A Major Fungal Pathogen of Humans)
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Article
Antifungal Activity of Capridine β as a Consequence of Its Biotransformation into Metabolite Affecting Yeast Topoisomerase II Activity
Pathogens 2021, 10(2), 189; https://doi.org/10.3390/pathogens10020189 - 09 Feb 2021
Viewed by 688
Abstract
In the last few years, increasing importance is attached to problems caused by fungal pathogens. Current methods of preventing fungal infections remain unsatisfactory. There are several antifungal compounds which are highly effective in some cases, however, they have limitations in usage: Nephrotoxicity and [...] Read more.
In the last few years, increasing importance is attached to problems caused by fungal pathogens. Current methods of preventing fungal infections remain unsatisfactory. There are several antifungal compounds which are highly effective in some cases, however, they have limitations in usage: Nephrotoxicity and other adverse effects. In addition, the frequent use of available fungistatic drugs promotes drug resistance. Therefore, there is an urgent need for the development of a novel antifungal drug with a different mechanism of action, blocking of the fungal DNA topoisomerases activity appear to be a promising idea. According to previous studies on the m-AMSA moderate inhibitory effect on fungal topoisomerase II, we have decided to study Capridine β (also acridine derivative) antifungal activity, as well as its inhibitory potential on yeast topoisomerase II (yTOPOII). Results indicated that Capridine β antifungal activity depends on the kind of strains analyzed (MICs range 0.5–64 μg mL−1) and is related to its biotransformation in the cells. An investigation of metabolite formation, identified as Capridine β reduction product (IE1) by the fungus Candida albicans was performed. IE1 exhibited no activity against fungal cells due to an inability to enter the cells. Although no antifungal activity was observed, in contrast to Capridine β, biotransformation metabolite totally inhibited the yTOPOII-mediated relaxation at concentrations lower than detected for m-AMSA. The closely related Capridine β only slightly diminished the catalytic activity of yTOPOII. Full article
(This article belongs to the Special Issue Candida albicans: A Major Fungal Pathogen of Humans)
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Review

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Review
From Jekyll to Hyde: The Yeast–Hyphal Transition of Candida albicans
Pathogens 2021, 10(7), 859; https://doi.org/10.3390/pathogens10070859 - 07 Jul 2021
Viewed by 828
Abstract
Candida albicans is a major fungal pathogen of humans, accounting for 15% of nosocomial infections with an estimated attributable mortality of 47%. C. albicans is usually a benign member of the human microbiome in healthy people. Under constant exposure to highly dynamic environmental [...] Read more.
Candida albicans is a major fungal pathogen of humans, accounting for 15% of nosocomial infections with an estimated attributable mortality of 47%. C. albicans is usually a benign member of the human microbiome in healthy people. Under constant exposure to highly dynamic environmental cues in diverse host niches, C. albicans has successfully evolved to adapt to both commensal and pathogenic lifestyles. The ability of C. albicans to undergo a reversible morphological transition from yeast to filamentous forms is a well-established virulent trait. Over the past few decades, a significant amount of research has been carried out to understand the underlying regulatory mechanisms, signaling pathways, and transcription factors that govern the C. albicans yeast-to-hyphal transition. This review will summarize our current understanding of well-elucidated signal transduction pathways that activate C. albicans hyphal morphogenesis in response to various environmental cues and the cell cycle machinery involved in the subsequent regulation and maintenance of hyphal morphogenesis. Full article
(This article belongs to the Special Issue Candida albicans: A Major Fungal Pathogen of Humans)
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Review
Invasive Candida Infections in Neonates after Major Surgery: Current Evidence and New Directions
Pathogens 2021, 10(3), 319; https://doi.org/10.3390/pathogens10030319 - 09 Mar 2021
Viewed by 639
Abstract
Infections represent a serious health problem in neonates. Invasive Candida infections (ICIs) are still a leading cause of mortality and morbidity in neonatal intensive care units (NICUs). Infants hospitalized in NICUs are at high risk of ICIs, because of several risk factors: broad [...] Read more.
Infections represent a serious health problem in neonates. Invasive Candida infections (ICIs) are still a leading cause of mortality and morbidity in neonatal intensive care units (NICUs). Infants hospitalized in NICUs are at high risk of ICIs, because of several risk factors: broad spectrum antibiotic treatments, central catheters and other invasive devices, fungal colonization, and impaired immune responses. In this review we summarize 19 published studies which provide the prevalence of previous surgery in neonates with invasive Candida infections. We also provide an overview of risk factors for ICIs after major surgery, fungal colonization, and innate defense mechanisms against fungi, as well as the roles of different Candida spp., the epidemiology and costs of ICIs, diagnosis of ICIs, and antifungal prophylaxis and treatment. Full article
(This article belongs to the Special Issue Candida albicans: A Major Fungal Pathogen of Humans)
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