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Antibiotics
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Research on the Pathogenesis of Candida albicans and Other Candida...
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Research on the Pathogenesis of Candida albicans and Other Candida Species

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Genetic and Biochemical Studies of Antibiotic Activity and Resistance".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 13609

Special Issue Editor

Dr. Samir Jawhara

E-Mail Website
Guest Editor
CNRS-UMR 8576, Inserm U1285, University Lille, Lille, France
Interests: Candida species; multidrug-resistant fungi; anti-fungal drugs; modulation of the immune response; intestinal inflammation; gut microbiota; anti-yeast glycan antibodies; fungal cell wall; intravenous immunoglobulin (IVIg); TLRs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Candida albicans remains the most prevalent Candida species causing fungal infections in humans, and is the causative agent of candidaemia and disseminated invasive candidiasis, leading to severe morbidity in millions of individuals worldwide. C. albicans and other Candida species are normally harmless commensal yeasts within the normal microbiota. In the commensal phase, C. albicans most likely lives in the mucus layer of mucosal surfaces but under certain pathophysiological circumstances, C. albicans may adhere directly to host epithelial cells and this interaction event contributes to Candida overgrowth and epithelial invasion, followed by disease and immune activation. C. albicans infections can generate anti-yeast glycan antibodies that are described as serological markers of Crohn's disease. These anti-glycan antibodies support a link between Crohn's disease gut dysbiosis and Candida species.

The aim of this Special Issue is to update the current knowledge of the pathogenesis of Candida species in patients with candidiasis and the rise of new multidrug-resistant fungi, the fungal cell wall, and the new antifungal drugs. Additionally, this Special Issue will also cover the virulence factors of Candida, their interaction with the host cells, and how these fungi are able to modulate the immune response and inflammation.

We especially encourage the submission of original manuscripts and reviews.

Dr. Samir Jawhara
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. 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 2900 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
  • Candida glabrata
  • Candida species
  • multidrug-resistant fungi
  • anti-fungal drugs
  • candidiasis
  • immune response
  • intestinal inflammation, gut microbiota
  • anti-yeast glycan antibodies
  • fungal cell wall
  • chitin
  • β-glucans
  • mannans

Published Papers (5 papers)

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Research

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12 pages, 1739 KiB  
Article
Unexpected Candidal Hyphae in Oral Mucosa Lesions—A Clinico-Pathological Study
by Jeremy Edel, Osnat Grinstein-Koren, Orit Winocur-Arias, Ilana Kaplan, Anna Schnaiderman-Shapiro, Amos Buchner, Marilena Vered and Ayelet Zlotogorski-Hurvitz
Antibiotics 2022, 11(10), 1386; https://doi.org/10.3390/antibiotics11101386 - 10 Oct 2022
Cited by 1 | Viewed by 1376
Abstract
Background: Oral mucosal biopsies might harbor candidal hyphae (CH) in the absence of any clinical signs or symptoms. Aim: To assess oral mucosa biopsies for the frequency of unexpected CH and characterize their clinico-pathological features. Materials and Methods: All biopsy reports (2004–2019) were [...] Read more.
Background: Oral mucosal biopsies might harbor candidal hyphae (CH) in the absence of any clinical signs or symptoms. Aim: To assess oral mucosa biopsies for the frequency of unexpected CH and characterize their clinico-pathological features. Materials and Methods: All biopsy reports (2004–2019) were searched using CH/candida/candidiasis as key words. Cases with clinical diagnosis of oral candidiasis (OC) were excluded. Demographic data, health status, smoking habits, clinical features and diagnoses were collected. Statistical analysis included the chi-square test; significance was set at p < 0.05. Results: Of all the biopsies, 100 (1.05%) reported microscopical evidence of CH without typical clinical signs/symptoms of OC. Fifteen cases were from healthy, non-smoking patients. CH was common on buccal mucosa (38%) and lateral tongue (23%). The tip of tongue (OR = 54.5, 95% CI 9.02–329.4, p < 0.001) and lateral tongue (OR = 3.83, 95% CI 2.4–6.09, p < 0.001) were more likely to harbor CH-positive lesions. CH-positive lesions were diagnosed as epithelial hyperplasia (55%) and exophytic reactive lesions (30%). No correlation was found between CH and the grade of epithelial dysplasia. Conclusions: Microscopic evidence of CH embedded into oral epithelium without typical signs/symptoms of OC is rare, especially in healthy, non-smokers. Since CH was occasionally found in oral sites prone to local trauma and in association with reactive lesions, in absence of host co-morbidities, the contribution of local mechanical forces to CH embedment cannot be ruled out. Full article
(This article belongs to the Special Issue Research on the Pathogenesis of Candida albicans and Other Candida Species)
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15 pages, 2285 KiB  
Article
Influence of Glucose on Candida albicans and the Relevance of the Complement FH-Binding Molecule Hgt1 in a Murine Model of Candidiasis
by Verena Harpf, Samyr Kenno, Günter Rambach, Verena Fleischer, Nadia Parth, Christian X. Weichenberger, Peter Garred, Silke Huber, Cornelia Lass-Flörl, Cornelia Speth and Reinhard Würzner
Antibiotics 2022, 11(2), 257; https://doi.org/10.3390/antibiotics11020257 - 16 Feb 2022
Cited by 3 | Viewed by 2087
Abstract
Candidiasis is common in diabetic patients. Complement evasion is facilitated by binding complement factor H (FH). Since the expression of high-affinity glucose transporter 1 (Hgt1), a FH-binding molecule, is glucose-dependent, we aimed to study its relevance to the pathogenesis of Candida albicans. [...] Read more.
Candidiasis is common in diabetic patients. Complement evasion is facilitated by binding complement factor H (FH). Since the expression of high-affinity glucose transporter 1 (Hgt1), a FH-binding molecule, is glucose-dependent, we aimed to study its relevance to the pathogenesis of Candida albicans. Euglycemic and diabetic mice were intravenously challenged with either Candida albicans lacking Hgt1 (hgt1-/-) or its parental strain (SN152). Survival and clinical status were monitored over 14 days. In vitro, Candida albicans strains were grown at different glucose concentrations, opsonized with human serum, and checked for C3b/iC3b and FH deposition. Phagocytosis was studied by fluorescein isothiocyanate-labeled opsonized yeast cells incubated with granulocytes. The murine model demonstrated a significantly higher virulence of SN152 in diabetic mice and an overall increased lethality of mice challenged with hgt1-/-. In vitro lower phagocytosis and C3b/iC3b deposition and higher FH deposition were demonstrated for SN152 incubated at higher glucose concentrations, while there was no difference on hgt1-/- at physiological glucose concentrations. Despite C3b/iC3b and FH deposition being glucose-dependent, this effect has a minor influence on phagocytosis. The absence of Hgt1 is diminishing this dependency on complement deposition, but it cannot be attributed to being beneficial in a murine model. Full article
(This article belongs to the Special Issue Research on the Pathogenesis of Candida albicans and Other Candida Species)
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16 pages, 5373 KiB  
Article
Two New Compounds Containing Pyridinone or Triazine Heterocycles Have Antifungal Properties against Candida albicans
by Laura Mena, Muriel Billamboz, Rogatien Charlet, Bérangère Desprès, Boualem Sendid, Alina Ghinet and Samir Jawhara
Antibiotics 2022, 11(1), 72; https://doi.org/10.3390/antibiotics11010072 - 08 Jan 2022
Cited by 11 | Viewed by 2066
Abstract
Candidiasis, caused by the opportunistic yeast Candida albicans, is the most common fungal infection today. Resistance of C. albicans to current antifungal drugs has emerged over the past decade leading to the need for novel antifungal agents. Our aim was to select [...] Read more.
Candidiasis, caused by the opportunistic yeast Candida albicans, is the most common fungal infection today. Resistance of C. albicans to current antifungal drugs has emerged over the past decade leading to the need for novel antifungal agents. Our aim was to select new antifungal compounds by library-screening methods and to assess their antifungal effects against C. albicans. After screening 90 potential antifungal compounds from JUNIA, a chemical library, two compounds, 1-(4-chlorophenyl)-4-((4-chlorophenyl)amino)-3,6-dimethylpyridin-2(1H)-one (PYR) and (Z)-N-(2-(4,6-dimethoxy-1,3,5-triazin-2-yl)vinyl)-4-methoxyaniline (TRI), were identified as having potential antifungal activity. Treatment with PYR and TRI resulted in a significant reduction of C. albicans bioluminescence as well as the number of fungal colonies, indicating rapid fungicidal activity. These two compounds were also effective against clinically isolated fluconazole- or caspofungin-resistant C. albicans strains. PYR and TRI had an inhibitory effect on Candida biofilm formation and reduced the thickness of the mannan cell wall. In a Caenorhabditis elegans infection model, PYR and TRI decreased the mortality of nematodes infected with C. albicans and enhanced the expression of antimicrobial genes that promote C. albicans elimination. Overall, PYR and TRI showed antifungal properties against C. albicans by exerting fungicidal activities and enhancing the antimicrobial gene expression of Caenorhabditis elegans. Full article
(This article belongs to the Special Issue Research on the Pathogenesis of Candida albicans and Other Candida Species)
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13 pages, 1091 KiB  
Article
The Antimicrobial Activity of Omiganan Alone and In Combination against Candida Isolated from Vulvovaginal Candidiasis and Bloodstream Infections
by Dawid Żyrek, Andrzej Wajda, Paulina Czechowicz, Joanna Nowicka, Maciej Jaśkiewicz, Damian Neubauer and Wojciech Kamysz
Antibiotics 2021, 10(8), 1001; https://doi.org/10.3390/antibiotics10081001 - 19 Aug 2021
Cited by 8 | Viewed by 2386
Abstract
Fungi from the Candida genus are widespread commensals and, at the same time, are the leading cause of fungal infections worldwide. For instance, vulvovaginal candidiasis (VVC) affects approximately 75% of women at least once in their lifetime, remaining the second most common gynecological [...] Read more.
Fungi from the Candida genus are widespread commensals and, at the same time, are the leading cause of fungal infections worldwide. For instance, vulvovaginal candidiasis (VVC) affects approximately 75% of women at least once in their lifetime, remaining the second most common gynecological infection. On the contrary, hospital-acquired fungal bloodstream infections (BSIs), although less frequent, are characterized by a high mortality rate. Undoubtedly, the main reason for this situation are virulence factors that these yeast-like fungi can produce, and the ability to form a biofilm is one of the most important of them. Due to the low effectiveness of classic antimycotics against Candida biofilms, an intense search for new drugs capable of eradicating this structure is highly demanded. One of the most promising groups of compounds exhibiting such properties are antimicrobial peptides (AMPs). This study focuses on a comparison of the efficacy of Omiganan and fluconazole alone and in combination against Candida strains isolated from BSIs. The obtained results are consistent with our previous reports on the effectiveness of Omiganan against clinical strains isolated from VVC. This is also the first report on the combinatory application of Omiganan in the context of fungal BSI. The majority of combinations with fluconazole showed an additive effect, as well as a synergistic effect in the range of certain concentrations. Importantly, such effects are visible at concentrations much lower than for those compounds used individually. Potentially, this entails the possibility of limiting the adverse effects (e.g., toxicity) of Omiganan and fluconazole applied in vivo, thus improving the safety profile of this particular antifungal therapy. Full article
(This article belongs to the Special Issue Research on the Pathogenesis of Candida albicans and Other Candida Species)
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Review

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12 pages, 667 KiB  
Review
How Fungal Glycans Modulate Platelet Activation via Toll-Like Receptors Contributing to the Escape of Candida albicans from the Immune Response
by Samir Jawhara
Antibiotics 2020, 9(7), 385; https://doi.org/10.3390/antibiotics9070385 - 07 Jul 2020
Cited by 10 | Viewed by 4485
Abstract
Platelets are essential for vascular repair and for the maintenance of blood homeostasis. They contribute to the immune defence of the host against many infections caused by bacteria, viruses and fungi. Following infection, platelet function is modified, and these cells form aggregates with [...] Read more.
Platelets are essential for vascular repair and for the maintenance of blood homeostasis. They contribute to the immune defence of the host against many infections caused by bacteria, viruses and fungi. Following infection, platelet function is modified, and these cells form aggregates with microorganisms leading, to a decrease in the level of circulating platelets. During candidaemia, mannans, β-glucans and chitin, exposed on the cell wall of Candida albicans, an opportunistic pathogenic yeast of humans, play an important role in modulation of the host response. These fungal polysaccharides are released into the circulation during infection and their detection allows the early diagnosis of invasive fungal infections. However, their role in the modulation of the immune response and, in particular, that of platelets, is not well understood. The structure and solubility of glycans play an important role in the orientation of the immune response of the host. This short review focuses on the effect of fungal β-glucans and chitin on platelet activation and how these glycans modulate platelet activity via Toll-like receptors, contributing to the escape of C. albicans from the immune response. Full article
(This article belongs to the Special Issue Research on the Pathogenesis of Candida albicans and Other Candida Species)
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