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Keywords = superficial fungal disease

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13 pages, 2427 KiB  
Perspective
Artificial Intelligence in the Histopathological Assessment of Non-Neoplastic Skin Disorders: A Narrative Review with Future Perspectives
by Mario Della Mura, Joana Sorino, Anna Colagrande, Maged Daruish, Giuseppe Ingravallo, Alessandro Massaro, Gerardo Cazzato, Carmelo Lupo, Nadia Casatta, Domenico Ribatti and Angelo Vacca
Med. Sci. 2025, 13(2), 70; https://doi.org/10.3390/medsci13020070 - 1 Jun 2025
Viewed by 1105
Abstract
Artificial intelligence (AI) is rapidly transforming diagnostic approaches in different fields of medical sciences, demonstrating an emerging potential to revolutionize dermatopathology due to its capacity to process large amounts of data in the shortest possible time, both for diagnosis and research purposes. Different [...] Read more.
Artificial intelligence (AI) is rapidly transforming diagnostic approaches in different fields of medical sciences, demonstrating an emerging potential to revolutionize dermatopathology due to its capacity to process large amounts of data in the shortest possible time, both for diagnosis and research purposes. Different AI models have been applied to neoplastic skin diseases, especially melanoma. However, to date, very few studies have investigated the role of AI in dermatoses. Herein, we provide an overview of the key aspects of AI and its functioning, focusing on medical applications. Then, we summarize all the existing English-language literature about AI applications in the field of non-neoplastic skin diseases: superficial perivascular dermatitis, psoriasis, fungal infections, onychomycosis, immunohistochemical characterization of inflammatory dermatoses, and differential diagnosis between the latter and mycosis fungoides (MF). Finally, we discuss the main challenges related to AI implementation in pathology. Full article
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24 pages, 2063 KiB  
Systematic Review
Global Dermatophyte Infections Linked to Human and Animal Health: A Scoping Review
by Aditya K. Gupta, Tong Wang, Susmita, Mesbah Talukder and Wayne L. Bakotic
Microorganisms 2025, 13(3), 575; https://doi.org/10.3390/microorganisms13030575 - 3 Mar 2025
Cited by 3 | Viewed by 3125
Abstract
Dermatophytes are commonly encountered pathogens in clinical practice causing superficial infections of the skin, hair, and nails. These pathogens are often found on animals such as livestock (e.g., cattle, rabbits) and pets (e.g., cats, hedgehogs) that can lead to spillover infections in human [...] Read more.
Dermatophytes are commonly encountered pathogens in clinical practice causing superficial infections of the skin, hair, and nails. These pathogens are often found on animals such as livestock (e.g., cattle, rabbits) and pets (e.g., cats, hedgehogs) that can lead to spillover infections in human populations. Here, we reviewed published reports (2009–2024) of dermatophyte infections in animals and in humans with a history of animal contact. A literature search was completed in October 2024 using PubMed, Embase (Ovid), and Web of Science (Core Collection), which identified 250 articles. Generally, dermatophytes tend to infect younger animals with long hair and exhibit a species-specific host range. Microsporum canis was the most commonly reported species—linked to cats—that can cause tinea capitis, especially concerning the development of kerion in children. Trichophyton verrucosum is strongly associated with cattle. The Trichophyton mentagrophytes complex shows a diverse range of animal hosts, with rabbits being most frequently reported; however, T. mentagrophytes var. erinacei is almost exclusively isolated from hedgehogs, and T. mentagrophytes var. benhamiae is more commonly found on rodents (e.g., guinea pigs). Lastly, the geophilic Nannizia gypsea has been isolated from both dogs and cats. Managing dermatophyte zoonoses is an ongoing challenge, as healthcare providers may empirically treat with corticosteroids or antibacterial agents due to its atypical inflammatory appearance. Evidence of in vitro resistance against griseofulvin and fluconazole has been documented in multiple zoonotic dermatophyte species. Resistance development against terbinafine and itraconazole is also a possibility, although the number of reports is scarce. Under the principles of the One Health approach, research on human fungal diseases should take animal and environmental factors into account. A renewed call for increased testing efforts is warranted. Full article
(This article belongs to the Special Issue Current Pattern in Epidemiology and Antifungal Resistance)
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12 pages, 2340 KiB  
Systematic Review
Macrophomina phaseolina: A Phytopathogen Associated with Human Ocular Infections—A Case Report of Endophthalmitis and Systematic Review of Human Infections
by Panagiotis Toumasis, Georgia Vrioni, Ioanna Gardeli, Aikaterini Michelaki, Maria Exindari and Maria Orfanidou
J. Clin. Med. 2025, 14(2), 430; https://doi.org/10.3390/jcm14020430 - 11 Jan 2025
Cited by 2 | Viewed by 1509
Abstract
Background: Macrophomina phaseolina is an important phytopathogenic fungus affecting over 500 plant species worldwide. However, this fungus rarely causes disease in humans. Methods: We reported the first case of endophthalmitis due to M. phaseolina, describing microbiological diagnostic approaches. Also, we [...] Read more.
Background: Macrophomina phaseolina is an important phytopathogenic fungus affecting over 500 plant species worldwide. However, this fungus rarely causes disease in humans. Methods: We reported the first case of endophthalmitis due to M. phaseolina, describing microbiological diagnostic approaches. Also, we performed a systematic review of human infections by this plant pathogen in literature. We searched PubMed, Scopus, and Web of Science databases from inception to 31 December 2024. Results: Our case involved a male patient who presented with photophobia and pain in his right eye. His recent medical history revealed a superficial corneal injury caused by a metal burr three months prior, managed unsuccessfully by topical treatment and subsequent conjunctival flap surgery two months later. Ophthalmological and microbiological investigations, including microscopic examination, cultures, and DNA sequencing of ocular specimens, revealed M. phaseolina endophthalmitis. Despite intravenous and intravitreal antifungal therapy, the patient’s condition continued to worsen, eventually leading to enucleation. Regarding the literature review, we identified 12 additional cases of M. phaseolina human infections previously reported in literature. Overall, M. phaseolina was primarily associated with ocular infections (76.9% of cases), followed by skin infections and combined skin–joint infections. The majority of patients with M. phaseolina infection (63.6%) had no known immunosuppressive factors. Clinical outcomes were unfavorable in 46.15% of cases. Conclusions: M. phaseolina is an emerging cause of human infections, even in immunocompetent hosts, with a predilection for ocular infections. Further research is warranted to elucidate the pathogenesis of fungal infections caused by plant pathogens in humans. Full article
(This article belongs to the Section Ophthalmology)
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17 pages, 3206 KiB  
Article
Sphaeropsidin A Loaded in Liposomes to Reduce Its Cytotoxicity and Preserve Antifungal Activity Against Candida auris
by Annalisa Buonanno, Maria Michela Salvatore, Antonia Feola, Antonietta Siciliano, Rosa Bellavita, Lorenzo Emiliano Imbò, Marco Guida, Anna Andolfi, Rosario Nicoletti, Angela Maione, Annarita Falanga and Emilia Galdiero
Molecules 2024, 29(24), 5949; https://doi.org/10.3390/molecules29245949 - 17 Dec 2024
Cited by 3 | Viewed by 1019
Abstract
Candida species constitute the most common cause of fungal infections in humans; the emergence of resistance and biofilm formation by Candida species further threaten the limited availability of antifungal agents. Over the past decade, C. auris has caused significant outbreaks worldwide and [...] Read more.
Candida species constitute the most common cause of fungal infections in humans; the emergence of resistance and biofilm formation by Candida species further threaten the limited availability of antifungal agents. Over the past decade, C. auris has caused significant outbreaks worldwide and has emerged as a human pathogenic fungus that causes diseases ranging from superficial to life-threatening disseminated infections. Despite the recent advances in antifungal research, the mechanisms of drug resistance in C. auris remain poorly understood even as its ability to form biofilms poses a significant therapeutic challenge. The purpose of this research was to elucidate the fungal properties of Sphaeropsidin A (SphA), a secondary metabolite derived from Diplodia fungi, with a specific focus on its efficacy against C. auris. This study revealed that SphA and its liposomal encapsulated (SphA-L) form are fungistatic with time-kill kinetics highlighting their efficacy and significantly inhibited the formation of C. auris biofilms. Our investigation into the antifungal mechanism of this drug revealed notable alterations in ROS production and the disruption of the Candida cell cycle. Our findings show that SphA-L impairs key pathogenic traits of C. auris, such as its ability to adhere to human epithelial cell lines, while exhibiting no harmful effects on human cells, highlighting its potential as a future therapeutic agent. In Caenorhabditis elegans infection models, both ShpA and SphA-L displayed effective antifungal activity, significantly reducing the C. auris fungal load and improving nematode survival rates, underscoring their promise as antifungal candidates. Overall, the potent antifungal effects of SphA and SphA-L against C. auris encourage further research. Full article
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15 pages, 1236 KiB  
Review
Genome-Scale Metabolic Models in Fungal Pathogens: Past, Present, and Future
by Angie Lorena Fonseca-Fernández, Andrés Fernando González Barrios and Adriana Marcela Celis Ramírez
Int. J. Mol. Sci. 2024, 25(19), 10852; https://doi.org/10.3390/ijms251910852 - 9 Oct 2024
Cited by 1 | Viewed by 2139
Abstract
Fungi are diverse organisms with various characteristics and functions. Some play a role in recycling essential elements, such as nitrogen and carbon, while others are utilized in the food and drink production industry. Some others are known to cause diseases in various organisms, [...] Read more.
Fungi are diverse organisms with various characteristics and functions. Some play a role in recycling essential elements, such as nitrogen and carbon, while others are utilized in the food and drink production industry. Some others are known to cause diseases in various organisms, including humans. Fungal pathogens cause superficial, subcutaneous, and systemic infections. Consequently, many scientists have focused on studying the factors contributing to the development of human diseases. Therefore, multiple approaches have been assessed to examine the biology of these intriguing organisms. The genome-scale metabolic models (GEMs) have demonstrated many advantages to microbial metabolism studies and the ability to propose novel therapeutic alternatives. Despite significant advancements, much remains to be elucidated regarding the use of this tool for investigating fungal metabolism. This review aims to compile the data provided by the published GEMs of human fungal pathogens. It gives specific examples of the most significant contributions made by these models, examines the advantages and difficulties associated with using such models, and explores the novel approaches suggested to enhance and refine their development. Full article
(This article belongs to the Special Issue Yeast as a Model System to Study Human Diseases)
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24 pages, 4008 KiB  
Review
Humans vs. Fungi: An Overview of Fungal Pathogens against Humans
by Kasun M. Thambugala, Dinushani A. Daranagama, Danushka S. Tennakoon, Dona Pamoda W. Jayatunga, Sinang Hongsanan and Ning Xie
Pathogens 2024, 13(5), 426; https://doi.org/10.3390/pathogens13050426 - 17 May 2024
Cited by 12 | Viewed by 9714
Abstract
Human fungal diseases are infections caused by any fungus that invades human tissues, causing superficial, subcutaneous, or systemic diseases. Fungal infections that enter various human tissues and organs pose a significant threat to millions of individuals with weakened immune systems globally. Over recent [...] Read more.
Human fungal diseases are infections caused by any fungus that invades human tissues, causing superficial, subcutaneous, or systemic diseases. Fungal infections that enter various human tissues and organs pose a significant threat to millions of individuals with weakened immune systems globally. Over recent decades, the reported cases of invasive fungal infections have increased substantially and research progress in this field has also been rapidly boosted. This review provides a comprehensive list of human fungal pathogens extracted from over 850 recent case reports, and a summary of the relevant disease conditions and their origins. Details of 281 human fungal pathogens belonging to 12 classes and 104 genera in the divisions ascomycota, basidiomycota, entomophthoromycota, and mucoromycota are listed. Among these, Aspergillus stands out as the genus with the greatest potential of infecting humans, comprising 16 species known to infect humans. Additionally, three other genera, Curvularia, Exophiala, and Trichophyton, are recognized as significant genera, each comprising 10 or more known human pathogenic species. A phylogenetic analysis based on partial sequences of the 28S nrRNA gene (LSU) of human fungal pathogens was performed to show their phylogenetic relationships and clarify their taxonomies. In addition, this review summarizes the recent advancements in fungal disease diagnosis and therapeutics. Full article
(This article belongs to the Special Issue An Update on Fungal Infections)
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31 pages, 4027 KiB  
Review
Atypical and Unpredictable Superficial Mycosis Presentations: A Narrative Review
by Zoubir Belmokhtar, Samira Djaroud, Derouicha Matmour and Yassine Merad
J. Fungi 2024, 10(4), 295; https://doi.org/10.3390/jof10040295 - 18 Apr 2024
Cited by 3 | Viewed by 4823
Abstract
While typically exhibiting characteristic features, fungal infections can sometimes present in an unusual context, having improbable localization (eyelid, face, or joint); mimicking other skin diseases such as eczema, psoriasis, or mycosis fungoides; and appearing with unexpected color, shape, or distribution. The emergence of [...] Read more.
While typically exhibiting characteristic features, fungal infections can sometimes present in an unusual context, having improbable localization (eyelid, face, or joint); mimicking other skin diseases such as eczema, psoriasis, or mycosis fungoides; and appearing with unexpected color, shape, or distribution. The emergence of such a challenging clinical picture is attributed to the complex interplay of host characteristics (hygiene and aging population), environment (climate change), advances in medical procedures, and agent factors (fungal resistance and species emergence). We aim to provide a better understanding of unusual epidemiological contexts and atypical manifestations of fungal superficial diseases, knowing that there is no pre-established clinical guide for these conditions. Thus, a literature examination was performed to provide a comprehensive analysis on rare and atypical superficial mycosis as well as an update on certain fungal clinical manifestations and their significance. The research and standard data extraction were performed using PubMed, Medline, Scopus, and EMBASE databases, and a total of 222 articles were identified. This review covers published research findings for the past six months. Full article
(This article belongs to the Special Issue New Perspectives for Superficial Fungal Infections)
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11 pages, 1579 KiB  
Brief Report
Superficial Zoonotic Mycoses in Humans Associated with Cats
by Marcin Piorunek, Honorata Kubisiak-Rzepczyk, Aleksandra Dańczak-Pazdrowska, Tomasz Trafas and Jarosław Walkowiak
J. Fungi 2024, 10(4), 244; https://doi.org/10.3390/jof10040244 - 24 Mar 2024
Cited by 5 | Viewed by 3871
Abstract
Dermatophytosis is a superficial fungal skin infection common in humans around the world and is one of the many zoonotic skin diseases that cat owners are at risk of contracting. This retrospective study was conducted based on a detailed analysis of the results [...] Read more.
Dermatophytosis is a superficial fungal skin infection common in humans around the world and is one of the many zoonotic skin diseases that cat owners are at risk of contracting. This retrospective study was conducted based on a detailed analysis of the results of mycological examination and medical documentation of 56 patients diagnosed with cat-to-human dermatophytoses from January 2017 to July 2022. Zoonotic mycoses were diagnosed more frequently in young people and women. In children, lesions most often occurred in the scalp area, and in adults, in the glabrous skin area. Skin infections caused by Microsporum canis (M. canis) prevailed and were confirmed in 47 patients (83.9%). Trichophyton mentagrophytes (T. mentagrophytes) was found in nine (16.1%) patients. M. canis predominantly caused infections of the scalp, followed by lower limb infections. Hairy scalps were almost exclusively involved in children. The odds of diagnosing M. canis infection compared to T. mentagrophytes infection was significantly higher in the head than in other regions, especially among children. The positive predictive value of a direct macroscopic examination was relatively low. Full article
(This article belongs to the Special Issue Advances in Human and Zoonotic Dermatophytoses)
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12 pages, 786 KiB  
Article
Analytical Study on Current Trends in the Clinico-Mycological Profile among Patients with Superficial Mycoses
by Shreekant Tiwari, Monalisah Nanda, Swetalona Pattanaik, Ganiga Channaiah Shivakumar, Bukanakere Sangappa Sunila, Marco Cicciù and Giuseppe Minervini
J. Clin. Med. 2023, 12(9), 3051; https://doi.org/10.3390/jcm12093051 - 22 Apr 2023
Cited by 6 | Viewed by 3014
Abstract
Infections affecting the superficial keratinized layer of the skin, nails, and hair are referred to as dermatophytosis and dermatomycoses, which constitute the most common type of fungal infection that affects people. This clinical ailment has a prevalence of between 30 and 60% and [...] Read more.
Infections affecting the superficial keratinized layer of the skin, nails, and hair are referred to as dermatophytosis and dermatomycoses, which constitute the most common type of fungal infection that affects people. This clinical ailment has a prevalence of between 30 and 60% and is more common in India’s hot, muggy, tropical climate. Examining the prevalence of superficial mycoses (SM), their clinical symptoms, and the fungal species that were identified as the disease-causing agents were the main objectives of the current study. This study comprised 250 clinically confirmed patients with SM who visited our dermatology department over the course of a year. Skin scrapings, nail clippings, and hair samples were gathered, mounted, and cultured using KOH. Macroscopic examination of culture, tease mount, and phenotypic tests were used to identify the species. The age group of 11–20 years (29%) had the highest prevalence of SM out of the 250 clinically verified cases of the condition that were included in our study, followed by 21–30 years (20%) and 31–40 years (18%). Candida albicans, dermatophytes, and non-dermatophytic moulds were the three most prevalent fungal isolates. The most typical dermatophyte isolate was T. rubrum, which was primarily found in Tinea corporis (TCo), Tinea cruris (TCr), and Tinea faciei (TFa). T. mentagrophytes was the second most frequent isolate. According to our investigation, it was determined that non-dermatophytic moulds constitute a significant contributor to the development of SM in addition to dermatophytes. Full article
(This article belongs to the Special Issue New Insights into Regenerative Dentistry)
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41 pages, 2002 KiB  
Review
Clinical Manifestations of Human Exposure to Fungi
by Manuela Oliveira, Diana Oliveira, Carmen Lisboa, José Laerte Boechat and Luís Delgado
J. Fungi 2023, 9(3), 381; https://doi.org/10.3390/jof9030381 - 21 Mar 2023
Cited by 45 | Viewed by 13455
Abstract
Biological particles, along with inorganic gaseous and particulate pollutants, constitute an ever-present component of the atmosphere and surfaces. Among these particles are fungal species colonizing almost all ecosystems, including the human body. Although inoffensive to most people, fungi can be responsible for several [...] Read more.
Biological particles, along with inorganic gaseous and particulate pollutants, constitute an ever-present component of the atmosphere and surfaces. Among these particles are fungal species colonizing almost all ecosystems, including the human body. Although inoffensive to most people, fungi can be responsible for several health problems, such as allergic fungal diseases and fungal infections. Worldwide fungal disease incidence is increasing, with new emerging fungal diseases appearing yearly. Reasons for this increase are the expansion of life expectancy, the number of immunocompromised patients (immunosuppressive treatments for transplantation, autoimmune diseases, and immunodeficiency diseases), the number of uncontrolled underlying conditions (e.g., diabetes mellitus), and the misusage of medication (e.g., corticosteroids and broad-spectrum antibiotics). Managing fungal diseases is challenging; only four classes of antifungal drugs are available, resistance to these drugs is increasing, and no vaccines have been approved. The present work reviews the implications of fungal particles in human health from allergic diseases (i.e., allergic bronchopulmonary aspergillosis, severe asthma with fungal sensitization, thunderstorm asthma, allergic fungal rhinosinusitis, and occupational lung diseases) to infections (i.e., superficial, subcutaneous, and systemic infections). Topics such as the etiological agent, risk factors, clinical manifestations, diagnosis, and treatment will be revised to improve the knowledge of this growing health concern. Full article
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44 pages, 2206 KiB  
Review
Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases
by Donald C. Vinh
Pathogens 2023, 12(3), 456; https://doi.org/10.3390/pathogens12030456 - 14 Mar 2023
Cited by 6 | Viewed by 6702
Abstract
In medical mycology, the main context of disease is iatrogenic-based disease. However, historically, and occasionally, even today, fungal diseases affect humans with no obvious risk factors, sometimes in a spectacular fashion. The field of “inborn errors of immunity” (IEI) has deduced at least [...] Read more.
In medical mycology, the main context of disease is iatrogenic-based disease. However, historically, and occasionally, even today, fungal diseases affect humans with no obvious risk factors, sometimes in a spectacular fashion. The field of “inborn errors of immunity” (IEI) has deduced at least some of these previously enigmatic cases; accordingly, the discovery of single-gene disorders with penetrant clinical effects and their immunologic dissection have provided a framework with which to understand some of the key pathways mediating human susceptibility to mycoses. By extension, they have also enabled the identification of naturally occurring auto-antibodies to cytokines that phenocopy such susceptibility. This review provides a comprehensive update of IEI and autoantibodies that inherently predispose humans to various fungal diseases. Full article
(This article belongs to the Special Issue Infection in Inborn Errors of Immunity)
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26 pages, 700 KiB  
Review
Inborn Errors of Immunity Causing Pediatric Susceptibility to Fungal Diseases
by Peter Olbrich and Donald C. Vinh
J. Fungi 2023, 9(2), 149; https://doi.org/10.3390/jof9020149 - 22 Jan 2023
Cited by 4 | Viewed by 3561
Abstract
Inborn errors of immunity are a heterogeneous group of genetically determined disorders that compromise the immune system, predisposing patients to infections, autoinflammatory/autoimmunity syndromes, atopy/allergies, lymphoproliferative disorders, and/or malignancies. An emerging manifestation is susceptibility to fungal disease, caused by yeasts or moulds, in a [...] Read more.
Inborn errors of immunity are a heterogeneous group of genetically determined disorders that compromise the immune system, predisposing patients to infections, autoinflammatory/autoimmunity syndromes, atopy/allergies, lymphoproliferative disorders, and/or malignancies. An emerging manifestation is susceptibility to fungal disease, caused by yeasts or moulds, in a superficial or invasive fashion. In this review, we describe recent advances in the field of inborn errors of immunity associated with increased susceptibility to fungal disease. Full article
(This article belongs to the Special Issue Fungal Infections in Children 2022)
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14 pages, 6684 KiB  
Article
A Dual-Plasmid-Based CRISPR/Cas9-Mediated Strategy Enables Targeted Editing of pH Regulatory Gene pacC in a Clinical Isolate of Trichophyton rubrum
by Sanchita Sanchaya Dey, Sivaprakash Ramalingam and Bhupesh Taneja
J. Fungi 2022, 8(12), 1241; https://doi.org/10.3390/jof8121241 - 24 Nov 2022
Cited by 1 | Viewed by 4373
Abstract
Trichophyton rubrum is the most prevalent causative agent responsible for 80–90% of all known superficial fungal infections in humans, worldwide. Limited available methods for genetic manipulations have been one of the major bottlenecks in understanding relevant molecular mechanisms of disease pathogenesis in T. [...] Read more.
Trichophyton rubrum is the most prevalent causative agent responsible for 80–90% of all known superficial fungal infections in humans, worldwide. Limited available methods for genetic manipulations have been one of the major bottlenecks in understanding relevant molecular mechanisms of disease pathogenesis in T. rubrum. Here, a dual-plasmid-based CRISPR/Cas9 strategy to edit pH regulatory transcription factor, pacC, of a clinical isolate of T. rubrum by non-homologous end joining (NHEJ) repair is presented. A cas9–eGFP fusion that aids pre-screening of primary transformants through detection of GFP fluorescence is expressed from one plasmid while target-specific sgRNA from the other brings about mutagenesis of pacC with an overall efficiency of 33.8–37.3%. The mutants had reduced transcript levels of pacC at both acidic and alkaline pH with several morphological abnormalities. We believe this dual-plasmid-based CRISPR/Cas9 strategy will aid functional genomics studies, especially in non-lab-adapted clinical strains of T. rubrum. Full article
(This article belongs to the Section Fungal Genomics, Genetics and Molecular Biology)
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12 pages, 2803 KiB  
Article
The Bovhyaluronidase Azoximer (Longidaza®) Disrupts Candida albicans and Candida albicans-Bacterial Mixed Biofilms and Increases the Efficacy of Antifungals
by Alina Gatina, Elena Trizna, Alena Kolesnikova, Diana Baidamshina, Anna Gorshkova, Valentin Drucker, Mikhail Bogachev and Airat Kayumov
Medicina 2022, 58(12), 1710; https://doi.org/10.3390/medicina58121710 - 23 Nov 2022
Cited by 5 | Viewed by 3149
Abstract
Background and Objectives: Candida albicans causes various diseases ranging from superficial mycoses to life-threatening systemic infections often associated with biofilm formation, including mixed fungal–bacterial consortia. The biofilm matrix protects cells, making Candida extremely resistant to treatment. Here, we show that the bovhyaluronidase azoximer (Longidaza [...] Read more.
Background and Objectives: Candida albicans causes various diseases ranging from superficial mycoses to life-threatening systemic infections often associated with biofilm formation, including mixed fungal–bacterial consortia. The biofilm matrix protects cells, making Candida extremely resistant to treatment. Here, we show that the bovhyaluronidase azoximer (Longidaza®) in vitro destroys the biofilm formed by either C. albicans alone or mixed with bacteria, this way decreasing the concentrations of antimicrobials required for the pathogen’s eradication. Materials and Methods: Bovhyaluronidase azoximer, Longidaza® was obtained from NPO Petrovax Pharm Ltd., Moscow, Russia as lyophilized powder. The antifungal activity was assessed by microdilution assay and CFUs counting. Antibiofilm activity was evaluated via biofilms staining and scanning electron microscopy. Results: Thus, treatment with Longidaza® reduced the biofilm biomass of nine C. albicans clinical isolates by 30–60%, while mixed biofilms of C. albicans with various bacteria were destroyed by 30–40%. Furthermore, the concentration of fluconazole required to achieve a similar reduction of the residual respiratory activity of detached cell clumps of four C. albicans isolates has been reduced four-fold when combined with Longidaza®. While in the biofilm, two of four isolates became significantly more susceptible to fluconazole in combination with Longidaza®. Conclusion: Taken together, our data indicate that Longidaza® is capable of suppression of tissues and artificial surfaces biofouling by C. albicans biofilms, as well as facilitating drug penetration into the cell clumps, this way decreasing the effective MIC of antifungals. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnostics, and Therapeutics of Infectious Diseases)
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28 pages, 6755 KiB  
Article
Quality by Design Guided Development of Polymeric Nanospheres of Terbinafine Hydrochloride for Topical Treatment of Onychomycosis Using a Nano-Gel Formulation
by Vinam Puri, Anna Froelich, Parinbhai Shah, Shernelle Pringle, Kevin Chen and Bozena Michniak-Kohn
Pharmaceutics 2022, 14(10), 2170; https://doi.org/10.3390/pharmaceutics14102170 - 12 Oct 2022
Cited by 24 | Viewed by 4006
Abstract
Superficial fungal diseases of the skin and nails are an increasingly common occurrence globally, requiring effective topical treatment to avoid systemic adverse effects. Polymeric nanoparticles have demonstrated sustained and effective drug delivery in a variety of topical formulations. The aim of this project [...] Read more.
Superficial fungal diseases of the skin and nails are an increasingly common occurrence globally, requiring effective topical treatment to avoid systemic adverse effects. Polymeric nanoparticles have demonstrated sustained and effective drug delivery in a variety of topical formulations. The aim of this project was to develop polymeric antifungal nanospheres containing terbinafine hydrochloride (TBH) to be loaded into a hydrogel formulation for topical nail drug delivery. A quality by design (QbD) approach was used to achieve optimized particles with the desired quality target product profile (QTPP). Polyvinyl alcohol (PVA) at 2% w/v and a drug to polymer ratio of 1:4, together with a robust set of processes and material attributes, resulted in nanoparticles of 108.7 nm with a polydispersity index (PDI) of 0.63, 57.43% recovery, and other desirable characteristics such as zeta potential (ZP), particle shape, aggregation, etc. The nanospheres were incorporated into a carbomer-based gel, and the delivery of TBH through this formulation was evaluated by means of in vitro drug release testing (IVRT) and ex vivo nail permeation study. The gel containing the TBH nanospheres demonstrated a slower and controlled drug release profile compared with the control gel, in addition to a more efficient delivery into the nail. These antifungal nanospheres can be utilized for topical therapy of a multitude of superficial fungal infections. Full article
(This article belongs to the Special Issue Nano Drug Delivery System)
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