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1.
IDCases ; 37: e02060, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224872

RESUMEN

Here we present a case of atypical manifestation of Sporothrix schenkii infection where the patient complained solely of lymphadenopathy without any prior noticeable skin lesions. A Thai female who had been working in Malaysia presented to a healthcare facility with a three-month history of progressively larger and more painful lymphadenopathy at her right chin.

2.
Mycoses ; 67(9): e13792, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39248498

RESUMEN

BACKGROUND: Zoonotic sporotrichosis caused by Sporothrix brasiliensis has become the main subcutaneous mycosis in Brazil. Minas Gerais (MG) is located in southeast Brazil and since 2015 has experienced an epidemic of zoonotic sporotrichosis. OBJECTIVES: This study aimed to reconstruct the epidemiological scenario of sporotrichosis from S. brasiliensis in recent epizooty in the Metropolitan Region of Belo Horizonte (MRBH), MG. METHODS: A total of 95 Sporothrix spp. isolates (Sporothirx brasiliensis n = 74, S. schenckii n = 11 and S. globosa n = 10) were subjected to Amplified Fragment Length Polymorphism (AFLP) genotyping and mating-type analysis to determine genetic diversity and population structure. Of these, 46 S. brasiliensis isolates were recovered from animals (cats n = 41 and dogs n = 5) from MRBH. RESULTS: Our study describes the high interspecific differentiation power of AFLP-based genotyping between the main phylogenetic Sporothrix groups. S. brasiliensis presents high genetic variability and pronounced population structure with geographically focused outbreaks in Brazil. The genetic groups include older genotypes from the prolonged epidemic in Southeast (Rio de Janeiro and São Paulo), South (Rio Grande do Sul), Northeast (Pernambuco) and new genotypes from the MRBH. Furthermore, we provide evidence of heterothallism mating strategy in pathogenic Sporothrix species. Genotypes originating in Rio de Janeiro and Pernambuco carry the predominant MAT1-2 idiomorph as opposed to genotypes from Rio Grande do Sul, which have the MAT1-1 idiomorph. We observed an overwhelming occurrence of MAT1-1 among MRBH isolates. CONCLUSION: Our study provides clear evidence of the predominance of a genetic group profile circulating in animals in Minas Gerais, independent of that disseminated from Rio de Janeiro. Our data can help us understand the genetic population processes that drive the evolution of this fungus in Minas Gerais and contribute to future mitigation actions for this ongoing epidemic.


Asunto(s)
Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Enfermedades de los Gatos , Epidemias , Variación Genética , Genotipo , Sporothrix , Esporotricosis , Esporotricosis/epidemiología , Esporotricosis/microbiología , Brasil/epidemiología , Sporothrix/genética , Sporothrix/clasificación , Sporothrix/aislamiento & purificación , Animales , Gatos , Perros , Enfermedades de los Gatos/microbiología , Enfermedades de los Gatos/epidemiología , Zoonosis/epidemiología , Zoonosis/microbiología , Filogenia , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/microbiología , Humanos
3.
Clin Cosmet Investig Dermatol ; 17: 1981-1983, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247137

RESUMEN

Sporotrichosis is a common chronic fungal infection and the clinical manifestations are often untypical. Diagnosis of sporotrichosis relies conventionally on fungal culture, histopathological examination, and species identification by molecular test. We reported that a 70-year-old man presented with a cutaneous lesion on the back of his right hand (present for 6 months). The cutaneous bacterial infection was diagnosed at a local hospital and the lesion had not improved. Physical examination revealed an infiltrative reddish plaque with purulent secretion and crusts. Histopathological examination revealed scattered round yeast cells in the dermis. Fungal culture revealed multiple, velvety, brown colonies on Sabouraud dextrose agar (SDA). Sporothrix globosa was identified by PCR-sequencing and next generation sequencing (NGS) method. Finally, a case of sporotrichosis caused by Sporothrix globosa was diagnosed by histopathological examination, mycological examination, and molecular identification. The patient was treated with oral itraconazole 400 mg/day for 2 months. The lesion was dramatically ameliorated.

4.
Infect Drug Resist ; 17: 3265-3272, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39100382

RESUMEN

Purpose: This study aimed to improve the understanding of sporotrichosis by analyzing the epidemiological characteristics, clinical manifestations, mycological features, and pathological characteristics of the disease in eastern China. Methods: Clinical data of 49 patients diagnosed with cutaneous sporotrichosis in dermatology clinics over a 20-year period were collected and analyzed retrospectively. The analysis included patient demographics, occupations, clinical types, lesion sites, misdiagnosis rates, laboratory investigations, treatment and outcomes. Results: The study included 22 male and 27 female patients, with a mean age of 52.4 years. Farmers (42.86%) and manual workers (28.57%) had a higher risk of infection. The most common clinical types were lymphocutaneous (30.61%) and fixed (69.39%), predominantly affecting the face and upper limbs. Misdiagnosis as other infectious skin diseases occurred in 35 patients (71.43%). Fungal culture and histopathological examination were important diagnostic tools. Treatment with oral itraconazole for three months led to relief and regression of the skin lesions in most patients, although a few experienced recurrences. Conclusion: Cutaneous sporotrichosis mainly affects individuals working in agriculture and manual labour, with lymphocutaneous and fixed types being the predominant clinical manifestations. The high misdiagnosis rate emphasizes the importance of early recognition, accurate diagnosis and standardized treatment for the prognosis and cure of sporotrichosis. Fungal culture and histopathological examination are essential for diagnosis, and oral itraconazole is an effective treatment option.

5.
Heliyon ; 10(14): e34444, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39113973

RESUMEN

Mycobacterium marinum(M. marinum ), a slow-growing bacterium in freshwater and seawater, can cause cutanous and extracutaneous infections. A fisher-woman with systemic lupus erythematosus (SLE) presented with chronic polymorphic rashes in a lymphangitic pattern was initially misdiagnosed as sporotrichosis. The final diagnosis of M. marinum and Candida dubliniensis co-infection was confirmed based on the skin histopathology, pustule culture, MetaCAP sequencing and effective antibiotic combination treatments.

6.
S Afr J Infect Dis ; 39(1): 648, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114260

RESUMEN

Sporothrix schenckii is a thermally dimorphic fungus found in soil and in plant matter. Cutaneous sporotrichosis is the most common manifestation and disseminated sporotrichosis is the rarest. Delayed diagnoses are not uncommon. We report a case of disseminated sporotrichosis involving the skin, bones and joints, with subsequent joint destruction, tissue loss and permanent disability. Contribution: This case report highlights the debilitating potential of sporotrichosis and its often elusive nature regarding diagnosis.

7.
J Med Microbiol ; 73(8)2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39145374

RESUMEN

Introduction. Sporotrichosis is a subcutaneous infection caused by dimorphic Sporothrix species embedded in the clinical clade. Fungi have virulence factors, such as biofilm and melanin production, which contribute to their survival and are related to the increase in the number of cases of therapeutic failure, making it necessary to search for new options.Gap statement. Proton pump inhibitors (PPIs) have already been shown to inhibit the growth and melanogenesis of other fungi.Aim. Therefore, this study aimed to evaluate the effect of the PPIs omeprazole (OMP), rabeprazole (RBP), esomeprazole, pantoprazole and lansoprazole on the susceptibility and melanogenesis of Sporothrix species, and their interactions with itraconazole, terbinafine and amphotericin B.Methodology. The antifungal activity of PPIs was evaluated using the microdilution method, and the combination of PPIs with itraconazole, terbinafine and amphotericin B was assessed using the checkerboard method. The assessment of melanogenesis inhibition was assessed using grey scale.Results. The OMP and RBP showed significant MIC results ranging from 32 to 256 µg ml-1 and 32 to 128 µg ml-1, respectively. Biofilms were sensitive, with a significant reduction (P<0.05) in metabolic activity of 52% for OMP and 50% for RBP at a concentration of 512 µg ml-1 and of biomass by 53% for OMP and 51% for RBP at concentrations of 512 µg ml-1. As for the inhibition of melanogenesis, only OMP showed inhibition, with a 54% reduction.Conclusion. It concludes that the PPIs OMP and RBP have antifungal activity in vitro against planktonic cells and biofilms of Sporothrix species and that, in addition, OMP can inhibit the melanization process in Sporothrix species.


Asunto(s)
Anfotericina B , Antifúngicos , Melanogénesis , Inhibidores de la Bomba de Protones , Sporothrix , Esporotricosis , Humanos , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Itraconazol/farmacología , Melaninas/biosíntesis , Melaninas/metabolismo , Melanogénesis/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/uso terapéutico , Sporothrix/efectos de los fármacos , Sporothrix/metabolismo , Esporotricosis/tratamiento farmacológico , Esporotricosis/microbiología , Terbinafina/farmacología
8.
J Fungi (Basel) ; 10(8)2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39194853

RESUMEN

Sporotrichosis is a type of zoonotic subcutaneous mycosis caused by different species of dimorphic fungus of the genus Sporothrix, and it is the most common form of subcutaneous mycosis in Latin America. Sporotrichosis is generally restricted to cutaneous and lymphatic tissue (i.e., localized forms), and involvement in the viscera (i.e., disseminated or disseminated cutaneous form) is uncommon, especially in the central nervous system. However, immunosuppression in individuals with diabetes mellitus can lead to the disseminated form of the disease due to a failure to eliminate the pathogen and poor infection treatment outcomes. Possible correlations between patients with diabetes and their greater susceptibility to disseminated cases of sporotrichosis include a decreased cytokine response after stimulation, increased oxidative stress, decreased chemotaxis, phagocytic activity, adhesion and rolling of neutrophils and monocytes/macrophages, and increased macrophage/monocyte and polymorphonuclear cell apoptosis. Therefore, this review highlights novel insights into diabetes and sporotrichosis by investigating how chronic inflammation affects and aggravates the infection, the possible causes of the greater susceptibility of Sporothrix sp. to hematogenous dissemination in immunocompromised patients, and the main alterations that this dissemination can cause.

9.
Microbiol Spectr ; : e0047424, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39194287

RESUMEN

Sporotrichosis, the cutaneous mycosis most commonly reported in Latin America, is caused by the Sporothrix clinical clade species, including Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. Due to its zoonotic transmission in Brazil, S. brasiliensis represents a significant health threat to humans and domestic animals. Itraconazole, terbinafine, and amphotericin B are the most used antifungals for treating sporotrichosis. However, many strains of S. brasiliensis and S. schenckii have shown resistance to these agents, highlighting the importance of finding new therapeutic options. Here, we demonstrate that milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, is a possible therapeutic alternative for the treatment of sporotrichosis, as observed by its fungicidal activity in vitro against different strains of S. brasiliensis and S. schenckii. Fluorescent miltefosine localizes to the Sporothrix cell membrane and mitochondria and causes cell death through increased permeabilization. Milteforan decreases S. brasiliensis fungal burden in A549 pulmonary cells and bone marrow-derived macrophages and also has an immunomodulatory effect by decreasing TNF-α, IL-6, and IL-10 production. Our results suggest milteforan as a possible alternative to treat feline sporotrichosis. IMPORTANCE: Sporotrichosis is an endemic disease in Latin America caused by different species of Sporothrix. This fungus can infect domestic animals, mainly cats and eventually dogs, as well as humans. Few drugs are available to treat this disease, such as itraconazole, terbinafine, and amphotericin B, but resistance to these agents has risen in the last few years. Alternative new therapeutic options to treat sporotrichosis are essential. Here, we propose milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, as a possible therapeutic alternative for treating sporotrichosis. Milteforan decreases S. brasiliensis fungal burden in human and mouse cells and has an immunomodulatory effect by decreasing several cytokine production.

10.
Mycopathologia ; 189(4): 66, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39003373

RESUMEN

Cat-transmitted sporotrichosis is caused by the emerging fungal pathogen Sporothrix brasiliensis and constitutes a significant public health issue that affects people living in resource-poor urban centers in Brazil. The lack of knowledge about transmission dynamics makes it difficult to propose public health policies to contain the advance of sporotrichosis. We describe the recent emergence of 1,176 cases of sporotrichosis in cats (2016 to 2021) in the metropolitan region of Recife, Brazil, leading to significant zoonotic transmission and an overwhelming occurrence of S. brasiliensis as the etiological agent. Most cases were from cats in the cities of Olinda (408/1,176; 34.70%), Jaboatão dos Guararapes (332/1,176; 28.23%), and Recife (237/1,176; 20.15%). Molecular typing using amplified fragment length polymorphism (EcoRI-GA/MseI-AG) revealed low polymorphic information content (PIC = 0.2499) and heterozygosity (H = 0.2928), typical of an outbreak scenario. Dendrogram and multivariate cluster analysis revealed that isolates from Pernambuco are closely related to Rio de Janeiro isolates. We report a substantial occurrence of MAT1-2 idiomorphs in the metropolitan region of Recife (0:60 ratio; χ2 = 60.000, P < 0.0001). The limited population differentiation and genetic diversity of the isolates from Pernambuco suggest a recent introduction, possibly via a founder effect, from the parental population in Rio de Janeiro. Our findings emphasize the critical importance of molecular surveillance of S. brasiliensis for outbreak response. A comprehensive one-health strategy is mandatory to control the spread of cat-transmitted sporotrichosis driven by S. brasiliensis, encompassing sanitary barriers, quick diagnosis, and treatment.


Asunto(s)
Enfermedades de los Gatos , Sporothrix , Esporotricosis , Esporotricosis/transmisión , Esporotricosis/microbiología , Esporotricosis/veterinaria , Esporotricosis/epidemiología , Gatos , Brasil/epidemiología , Sporothrix/genética , Sporothrix/aislamiento & purificación , Sporothrix/clasificación , Animales , Enfermedades de los Gatos/microbiología , Enfermedades de los Gatos/transmisión , Enfermedades de los Gatos/epidemiología , Tipificación Molecular , Zoonosis/transmisión , Zoonosis/microbiología , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Enfermedades Transmisibles Emergentes/transmisión , Enfermedades Transmisibles Emergentes/microbiología , Enfermedades Transmisibles Emergentes/epidemiología , Genotipo , Filogenia
11.
Future Microbiol ; 19(12): 1097-1106, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39056139

RESUMEN

Sporotrichosis, a mycosis resulting from cutaneous or subcutaneous infection with the dimorphic fungus Sporothrix, has been reported in China, particularly in the northeast region. In this review, we conducted a thorough examination of the recent advancements in sporotrichosis in China, encompassing aspects such as etiology, epidemiology, pathogenesis, clinical manifestations, diagnosis and treatment strategies. Within the Chinese context, fixed cutaneous sporotrichosis represents the prevailing clinical manifestation. Fungal culture stands as the gold standard for diagnosing sporotrichosis, while polymerase chain reaction techniques can enhance both the specificity and sensitivity of diagnosis. Besides conventional systemic antifungal agents, alternative modalities such as Chinese herbal medicines, photodynamic therapy and laser therapy show potential efficacy against sporotrichosis.


Sporotrichosis is a fungal infection on the skin. It is caused by a group of fungi called Sporothrix. Common symptoms are lesions on the skin, inflammatory papules, nodules and ulcers. These fungi live in the natural environment and cause infection by entering the body through a wound in the skin. China has a high prevalence of sporotrichosis, with northeast China the most seriously affected region. This review looks at the state of sporotrichosis in China.


Asunto(s)
Antifúngicos , Sporothrix , Esporotricosis , Esporotricosis/epidemiología , Esporotricosis/microbiología , Esporotricosis/tratamiento farmacológico , Esporotricosis/diagnóstico , China/epidemiología , Humanos , Sporothrix/aislamiento & purificación , Sporothrix/genética , Sporothrix/efectos de los fármacos , Antifúngicos/uso terapéutico , Reacción en Cadena de la Polimerasa , Fotoquimioterapia
12.
Prev Vet Med ; 230: 106275, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39043072

RESUMEN

The research addresses zoonotic sporotrichosis in Brazil, particularly caused by Sporothrix brasiliensis, highlighting its epidemiological severity. Transmission occurs through contact with sick animals, especially felines, and diagnosis in humans is challenging due to the low fungal load in the lesions. The study analyzed data from Information System for Notifiable Diseases (SINAN) and Zoonosis Surveillance Unit (UVZ) from January 2017 to March 2023, carried out in Contagem, Minas Gerais. Geospatial tools and statistical analysis revealed a significant increase in cases, peaking in 2021 for felines and 2022 for humans. The geospatial analysis highlighted areas of higher incidence, suggesting a correlation between human and feline populations. The research contributes to the understanding of sporotrichosis in Contagem, emphasizing the importance of integrated approaches for surveillance and control strategies, aiming to mitigate impacts on the local community.


Asunto(s)
Enfermedades de los Gatos , Esporotricosis , Zoonosis , Gatos , Animales , Esporotricosis/veterinaria , Esporotricosis/epidemiología , Esporotricosis/microbiología , Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/microbiología , Brasil/epidemiología , Zoonosis/epidemiología , Humanos , Incidencia , Análisis Espacio-Temporal , Sporothrix
13.
JAAD Case Rep ; 50: 69-71, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39044996
15.
J Fungi (Basel) ; 10(6)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38921408

RESUMEN

Despite the central role of cats in the transmission and amplification of Sporothrix, studies regarding immune response in feline sporotrichosis are scarce. In cats with sporotrichosis, neutrophil-rich lesions are usually associated to good general condition and lower fungal burden. However, the role of neutrophils in anti-Sporothrix immunity has been little explored in cats. Thus, the aim of this study was to evaluate the neutrophil oxidative burst in the blood of cats with sporotrichosis. Cats with sporotrichosis included in the study were treated with itraconazole (ITZ) alone or combined with potassium iodide (KI). The neutrophil oxidative burst was evaluated through a flow-cytometry-based assay using dihydrorhodamine 123 (background) and stimulation with Zymosan and heat-killed Sporothrix yeasts. The cure rate was 50.0% in cats under treatment with ITZ monotherapy and 90.9% in cats treated with ITZ + KI (p = 0.014), endorsing the combination therapy as an excellent alternative for the treatment of feline sporotrichosis. Higher percentages of Sporothrix-stimulated neutrophils were associated with good general condition (p = 0.003). Higher percentages of Sporothrix- (p = 0.05) and Zymosan-activated (p = 0.014) neutrophils before and early in the treatment were related to clinical cure in ITZ-treated cats. The correlation between oxidative burst and successful use of KI could not be properly assessed given the low number of failures (n = 2) in this treatment group. Nasal mucosa involvement, typically linked to treatment failure, was related to lower percentages of activated neutrophils in the background at the treatment outcome (p = 0.02). Our results suggest a beneficial role of neutrophils in feline sporotrichosis and a positive correlation between neutrophil activation and the cure process in ITZ-treated cats.

16.
Cureus ; 16(5): e59939, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38854294

RESUMEN

Sporotrichosis is a subcutaneous mycotic infection, caused by the dimorphic fungi Sporothrix schenckii. Ocular sporotrichosis has both intraocular and adnexal forms. We describe two cases of sporotrichosis involving the conjunctiva of two healthy individuals after inoculation by their pet cats, with complete resolution of lesions after antifungal treatment.

17.
J Am Acad Dermatol ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38852743

RESUMEN

In this part 1 of a 2-part continuing medical education series, the epidemiology, clinical features, and diagnostic methods for fungal skin neglected tropical diseases (NTDs), which include eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis, are reviewed. These infections, several of which are officially designated as NTDs by the World Health Organization (WHO), cause substantial morbidity and stigma worldwide and are receiving increased attention due to the potential for climate change-related geographic expansion. Domestic incidence may be increasing in the setting of global travel and immunosuppression. United States dermatologists may play a central role in early detection and initiation of appropriate treatment, leading to decreased morbidity and mortality.

18.
J Am Acad Dermatol ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38851491

RESUMEN

In this part 2 of a 2-part continuing medical education series, the management, outcomes, and morbidities for fungal skin neglected tropical diseases (NTDs), including eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis are reviewed. While fungal skin NTDs are associated with poverty in resource-limited settings, they are more often associated with immunosuppression and global migration in the United States. These infections have a high morbidity burden, including disfigurement, physical disability, coinfection, malignant transformation, mental health issues, and financial impact. For most fungal skin NTDs, management is difficult and associated with low cure rates. Dermatologists play a central role in initiating appropriate treatment early in disease course in order to improve patient outcomes.

19.
Front Cell Infect Microbiol ; 14: 1382508, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38828263

RESUMEN

Introduction: Sporotrichosis is a subcutaneous mycosis caused by fungi of the genus Sporothrix sp. Phenotypic and genotypic differences have been associated with their geographic distribution, virulence, or clinical manifestation of sporotrichosis. In the past decade, the interest in identifying species of the Sporothrix sp. has been increasing, due to its epidemiological importance and, in consequence, is important to know how to preserve them for future studies, in culture collection. Aims: The purposes of this study were to analyze the global distribution of environmental isolates and/or causal agents of sporotrichosis identified by polyphasic taxonomy, with mandatory use of molecular identification, and to evaluate the percentages and distribution of isolates stored in culture collections. Methods: A systematic review of articles on animal and human sporotrichosis and/or environmental isolation of the fungus, from 2007 to 2023, was done. Results: Our results demonstrated that, S. globosa, S. schenckii, and S. brasiliensis were the most identified species. With respect to the deposit and maintenance of species, we observed that only 17% of the strains of Sporothrix sp. isolated in the world are preserved in a culture collection. Conclusions: This systematic review confirmed a difficulty in obtaining the frequency of Sporothrix species stored in culture collection and insufficient data on the molecular identification mainly of animal sporotrichosis and isolation of Sporothrix sp. in environmental samples.


Asunto(s)
Sporothrix , Esporotricosis , Sporothrix/clasificación , Sporothrix/aislamiento & purificación , Sporothrix/genética , Esporotricosis/microbiología , Animales , Humanos , Microbiología Ambiental , Preservación Biológica/métodos
20.
Braz J Microbiol ; 55(3): 2655-2667, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38888692

RESUMEN

Sporotrichosis is recognized as the predominant subcutaneous mycosis in South America, attributed to pathogenic species within the Sporothrix genus. Notably, in Brazil, Sporothrix brasiliensis emerges as the principal species, exhibiting significant sapronotic, zoonotic and enzootic epidemic potential. Consequently, the discovery of novel therapeutic agents for the treatment of sporotrichosis is imperative. The present study is dedicated to the repositioning of pharmaceuticals for sporotrichosis therapy. To achieve this goal, we designed a pipeline with the following steps: (a) compilation and preparation of Sporothrix genome data; (b) identification of orthologous proteins among the species; (c) identification of homologous proteins in publicly available drug-target databases; (d) selection of Sporothrix essential targets using validated genes from Saccharomyces cerevisiae; (e) molecular modeling studies; and (f) experimental validation of selected candidates. Based on this approach, we were able to prioritize eight drugs for in vitro experimental validation. Among the evaluated compounds, everolimus and bifonazole demonstrated minimum inhibitory concentration (MIC) values of 0.5 µg/mL and 4.0 µg/mL, respectively. Subsequently, molecular docking studies suggest that bifonazole and everolimus may target specific proteins within S. brasiliensis- namely, sterol 14-α-demethylase and serine/threonine-protein kinase TOR, respectively. These findings shed light on the potential binding affinities and binding modes of bifonazole and everolimus with their probable targets, providing a preliminary understanding of the antifungal mechanism of action of these compounds. In conclusion, our research advances the understanding of the therapeutic potential of bifonazole and everolimus, supporting their further investigation as antifungal agents for sporotrichosis in prospective hit-to-lead and preclinical investigations.


Asunto(s)
Antifúngicos , Reposicionamiento de Medicamentos , Genoma Fúngico , Pruebas de Sensibilidad Microbiana , Sporothrix , Esporotricosis , Sporothrix/efectos de los fármacos , Sporothrix/genética , Antifúngicos/farmacología , Esporotricosis/microbiología , Esporotricosis/tratamiento farmacológico , Brasil , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Simulación del Acoplamiento Molecular , Genómica , Humanos , Evaluación Preclínica de Medicamentos , Descubrimiento de Drogas , Biología Computacional
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