Sporothrix Schenckii Complex Research Articles

Sporothrix schenckii complex in felines: Analysis of clinical, mycological, environmental and epidemiological factors

Sporotrichosis is an infectious and chronic fungal disease caused by fungi belonging to the Sporothrix schenckii complex that affects humans and animals through traumatic implantation of the fungus in the skin. They are dimorphic, saprophytic and geophilic fungi that are widely distributed in nature, especially in soils rich in organic matter. The aim of this study was to understand the clinical, mycological, environmental and epidemiological aspects of the Sporothrix schenckii complex in felines. In order to meet the objectives of this research, a qualitative, descriptive and exploratory data survey was carried out through a bibliographic review based on works published in the last 23 years. Sporothrix spp. is considered to be a complex of at least six cryptic species, in other words, they have similar morphological characteristics but different genotypes. In cats, the incubation period is variable; it usually lasts 14 days. On penetrating the tissue, the micellar form transforms into yeast, which generates an inflammatory response and proliferation of the microorganism at the site, causing papular and nodular lesions which, in some cases, heal spontaneously. Therefore, it is clear that sporotrichosis is caused by dimorphic fungi of the Sporothrix schenkii complex. It is a zoonotic disease of great importance in the context of public health, since it is still a neglected disease and requires robust measures to control. As well as being the most seriously affected, felines are the main transmitters to humans and animals, making them a key point in controlling outbreaks of the disease.

Lymphocutaneous Sporotrichosis

Sporotrichosis is a chronic subcutaneous mycosis caused by a fungus, Sporothrix schenckii complex. The first case in India was reported by Ghosh in 1932. The disease is prevalent primarily in the sub-Himalayan region, North-eastern states, and parts of Karnataka. Mostly seen in adults, it uncommonly presents in children over the face and limbs either as fixed cutaneous or lymphocutaneous form. Here, we present a case of 3-years-old boy hailing from Southern Tamil Nadu with multiple nodular lesions in linear fashion over the right upper limb. It was diagnosed as a case of lymphocutaneous sporotrichosis that developed following cut injury over the right index finger. We publish this case as it is rare to occur in this geographic location.

Development of a Versatile Toolbox for Genetic Manipulation of Sporothrix brasiliensis.

Sporothrix brasiliensis has emerged as the most virulent species in the Sporothrix schenckii complex, accounting for sporotrichosis. Albeit the new insights into the understanding of host-pathogen interactions and comparative genomics of this fungi, the lack of genetic tools has hindered significant advances in this field of research. Here, we established an Agrobacterium tumefaciens-mediated transformation (ATMT) system to transform different strains of S. brasiliensis. We report parameters that account for a transformation efficiency of 3,179 ± 1,171 transformants/co-cultivation, which include the use of A. tumefaciens AGL-1 in a 2:1 ratio (bacteria:fungi) during 72 h at 26°C. Our data show that a single-copy transgene is transferred to S. brasiliensis that is mitotically stable in 99% of cells after 10 generations without selective pressure. In addition, we created a plasmid toolkit that allows the establishment of fusion proteins of any S. brasiliensis gene of interest with sGFP or mCherry under the control of the GAPDH or H2A endogenous promoters. These modules allow different levels of expression of the desired fusion. Moreover, we successfully targeted these fluorescent proteins to the nucleus and used fluorescence-tagged strains to assess phagocytosis. Overall, our data show that the ATMT system is an easy-to-use and efficient genetic toolbox for studies on recombinant expression and gene function in S. brasiliensis. IMPORTANCE Sporotrichosis is the most prevalent subcutaneous mycosis worldwide and has recently become a public health concern. Although immunocompetent hosts are also prone to sporotrichosis, immunodeficient hosts often develop a more severe and disseminated form of disease. To date, the Rio de Janeiro state in Brazil is the most significant feline zoonotic transmission epicenter in the world, with more than 4,000 human and feline diagnosed cases. Cats play an essential role in the S. brasiliensis infection due to their high susceptibility and transmissibility to other felines and humans. S. brasiliensis is the most virulent etiological agent of sporotrichosis, causing the most severe clinical manifestations. Despite the increasing incidence of sporotrichosis, the identification of virulence traits important for disease establishment, development, and severity has been lacking. In this work, we established an efficient genetic toolbox to manipulate S. brasiliensis that will guide future studies to define new virulence mechanisms and a better understanding of host-pathogen interactions from a molecular perspective.

Feline sporotrichosis caused by Sporothrix schenckii sensu stricto in Southern Thailand: phenotypic characterization, molecular identification, and antifungal susceptibility.

Feline sporotrichosis caused by the Sporothrix schenckii complex is a global subcutaneous mycosis, having higher prevalence in Latin America and Malaysia. However, its etiological agents have not been elucidated in Thailand, a neighboring country of Malaysia, where the cases are increasing. This study identified 38 feline isolates of S. schenckii from Southern Thailand, collected between 2018 and 2021, using phenotypic characterization and molecular identification using polymerase chain reaction (PCR)-sequencing of partial calmodulin (CAL) and ß-tubulin (Bt2) genes. Phenotypic characteristics proved that the isolates were S. schenckii sensu lato, with low thermotolerance. Based on partial CAL and Bt2-PCR sequencing, all isolates were identified as S. schenckii sensu stricto. Phylogenetic analyses revealed that the isolates were clustered with S. schenckii sensu stricto isolated from the cats in Malaysia. A low degree of genetic diversity was observed among the Thai feline isolates. The antifungal susceptibility of these isolates to antifungal agents, including itraconazole (ITC), ketoconazole (KTC), fluconazole (FLC), and amphotericin B (AMB), was investigated according to the M27-A3 protocol of the Clinical and Laboratory Standards Institute. Results showed low ITC, KTC, and AMB activities against S. schenckii sensu stricto isolates, with high minimum inhibitory concentration (MIC) ranges of 1-8, 1-8, and 2-16μg/ml, respectively, whereas FLC exhibited MICs of 64 and>64μg/ml. This study indicated that S. schenckii sensu stricto is the causative agent responsible for feline sporotrichosis in Southern Thailand. Their phenotypic characteristics and in vitro antifungal susceptibility profiles will help to improve our understanding of this mycosis in Thailand.

P051 A case of recalcitrant sporotrichosis by infection of Sporothrix globosa

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM ObjectivesSporotrichosis is the leading subcutaneous mycosis caused by the Sporothrix (S.) schenckii complex. S. globosa is the causative organism of fixed sporotrichosis in Korea. The preferred regimen of cutaneous sporotrichosis is itraconazole for 3-6 months, however, there were few studies for recalcitrant sporotrichosis.MethodsIn 2018, we performed a histological examination of a patient who suffered sporotrichosis for 3 years and cultured part of the specimen. Despite various regimens for years, improvement and exacerbation were repeated, so we took another skin biopsy and cultured it in 2021. Isolates from the 2018 and 2021 lesions were identified as S. globosa by ribosomal DNA ITS sequencing (GenBank accession number: MH499862 and MH499863). The in vitro antifungal sensitivity tests were performed by broth microdilution method according to CLSI M38-A2 guidelines or Sensititre YeastOne® manufacturer's instructions. They were incubated at 30°C in a non-CO2 incubator for 7 days.ResultsIn 2018, histologically, we observed chronic inflammatory granuloma comprising lymphocytes, histiocytes, and giant cells, and several spores with periodic acid-Schiff (PAS) staining. Microscopic findings and ITS sequences of rRNA gene were identical with S. globosa. The antifungal susceptibility profile in 2018 revealed sensitive to terbinafine (0.125 μg/ml), and moderate to high MIC values for amphotericin B (2 μg/ml), itraconazole (>16 μg/ml), voriconazole (>16 μg/ml), and echinocandins (>16 μg/ml). Treatment with terbinafine, itraconazole, or amphotericin B, the skin lesions were partially improved, but were not cured. In 2021, we took another skin biopsy and culture specimen. Histopathological and mycological examination results were the same as before. The antifungal susceptibility profile revealed sensitive to itraconazole (0.5/ml), and high MIC for others. Clinically, skin lesions were not improved with the use of itraconazole 200 mg/d. Itraconazole 400 mg/d with local heating induced moderate improvement. There was no evidence of immune deficiency.ConclusionWe experienced recalcitrant sporotrichosis that did not respond to itraconazole and terbinafine, and the sensitivity of antifungal was changed. In this case, the combination treatment including local heating, saturated KI may be considered, and frequent antifungal susceptibility tests are needed.

Feline sporotrichosis: Review

Sporotrichosis is characterized as a zoonotic fungal infection caused by species of the Sporothrix schenckii complex that has been gaining importance in several regions of Brazil. In mammals the clinical picture presents in the chronic or acute form with the appearance of skin lesions and contaminated domestic felines present as one of its main vectors. The disease is considered a public health problem, since it mainly affects the population of endemic areas. Diagnosis is made with the identification and isolation of the fungus S. schenckii and the treatment of choice is carried out through the use of drugs of the class of azole antifungals such as ketoconazole, itraconazole and fluconazole. However, new treatment methods have been studied, such as the use of thymomodulin. Sporotrichosis is a neglected and still underdiagnosed disease, mainly due to lack of information and dissemination. In this context, taking into account its importance for the One Health, this review aims to address the definition of the disease in felines, as well as its etiopathogenesis, transmission, clinical signs, diagnosis, prophylaxis, control and the most current treatment tools.

Old and New Insights into Sporothrix schenckii Complex Biology and Identification.

Sporothrix schenckii is a worldwide-distributed thermally dimorphic fungus, which usually causes a subacute to chronic infection through traumatic implantation or inoculation of its infectious propagules. The fungus encompasses a group of phylogenetically closely related species, thus named the S. schenckii complex, of which S. schenckii sensu stricto and S. brasiliensis are main causative species of sporotrichosis. Owing to a multifaceted molecular dynamic, the S. schenckii complex can switch between the mycelium and the yeast form. This characteristic along with a varying cell wall composition account for significant species-specific differences in the host range, virulence, and susceptibility to antifungal drugs. While culture remains the gold standard to diagnose sporotrichosis, polymerase chain reaction (PCR) or matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry-based methods have become an essential for accurate species identification in many clinical laboratories. If directly applied on tissue samples, molecular methods are helpful to improve both sensitivity of and time to the etiological diagnosis of sporotrichosis. This mini-review aims to put together the old and new knowledge on the S. schenckii complex biology and identification, with particular emphasis on the laboratory diagnosis-related aspects of disease.

Feline Sporotrichosis in the periocular region - Successful Treatment with Itraconazole

Background: Sporotrichosis is a zoonotic disease caused by a dimorphic fungi of the Sporothrix schenckii complex. It is an emerging zoonosis with worldwide distribution, thus of great importance to public health. The infection occurs from traumatic inoculation of the fungus in the human skin from contaminated plants and soils and through bites or scratches of infected animals. The occurrence of sporotrichosis has been related to zoonotic transmission, especially by domestic felines. This work aims to report the successful use of itraconazole as monotherapy in a case of localized feline sporotrichosis and highlight the effectiveness of cytology in its diagnosis.Case: A 1-year-and-4-month-old spayed female cat undefined breed, weighing 3.1 kg, was referred to the Veterinary Medical Teaching Hospital of the Universidade Estadual de Maringá (UEM), city of Umuarama, presenting a serosanguinous ulcerative lesion located in the left periocular region The clinical picture of the patient progressed over 3 months. Treatments with antibiotic therapy, corticosteroids, and surgical procedures were conducted, without clinical improvement. A new lesion in the distal portion of the thoracic limb emerged, proving that the disease remained in progression. Hematological exams were performed, among them hemogram, renal and hepatic biochemical analyses, SNAPS to identify the feline immunodeficiency virus feline leukemia virus (FIV/FeLV), and cytology of the lesion through imprints. The hematological results were all within the normal standards for the species. Cytology showed a large amount of oval and fusiform structures phagocyted by polymorphonuclear cells, free at the bottom of the slide, compatible with Sporothrix spp. The treatment administered was itraconazole (100 mg/cat), orally administered every 24 h, cefovecin sodium 8 mg/kg, subcutaneous, single dose, topical use of antifungal ointment based on ketoconazole, twice a day. The animal underwent periodic physical and hematological evaluations throughout the treatment period, without significant changes. Complete remission of the lesion was observed after 25 weeks of treatment.Discussion: Cutaneous lesions caused by Sporothrix spp. are mainly located in the head, specifically in the nasal plane, pinna, and periocular regions, presenting ulcerative characteristics and exudate. The dissemination of the fungus through the animal's body may occur through autoinoculation while the feline scratches or licks itself. The cytology presents high sensitivity for diagnosing feline sporotrichosis due to the high fungal load found in the cutaneous lesions. In addition, it is a technique easy to perfom and presents immediate results, favoring an early beginning of the therapy. Itraconazole is considered the drug of choice for the treatment of sporotrichosis because of its efficacy and safety compared to that of other antifungal drugs. The average time of treatment is 4 to 9 months in cats, and it must be maintained for another month after complete remission of the clinical signs to prevent the reactivation of the lesions. FIV and FeLV are not predominant factors for the development of the disease. The use of itraconazole as monotherapy proved to be effective, with no side effects throughout the treatment. Cytology was satisfactory as a diagnostic method and allowed immediate initiation of therapy. Awareness regarding the forms of transmission and prevention of this zoonosis is instrumental.Keywords: Sporothrix spp., zoonosis, monotherapy, itraconazole, cytology.Título: Esporotricose felina na região periocular - eficácia do tratamento com itraconazol.Descritores: Sporothrix spp., zoonose, monoterapia, itraconazol, citologia.

First report of fungal Sporothrix schenckii complex isolation from feline with possible zoonotic transmission in the city of Belém, Pará, Brazil: Case report

Feline sporotrichosis is a subcutaneous, infectious, and contagious mycosis, with zoonotic characteristics. Until now there are no reports on the isolation of Sporothrix sp. in cats in the state of Pará. The present work aimed to isolate Sporothrix spp. from a cat with possible zoonotic involvement in the city of Belém, Pará. Through the active search for suspected cases of sporotrichosis, carried out by members of the Center for the Control of Zoonoses of Belém (CCZ, Belém) the suspicion of the disease in a feline was reported, with probable transmission to its owner. Clinical evaluation was performed, and biological material was collected from the animal for identifying the agent. Microscopic evaluation of the collected sample and microbial culture confirmed the presence of Sporothrix sp. in the sample. This study is the first to report the microbiological isolation of Sporothrix sp. in a cat in the metropolitan region of Belém, Pará, with possible zoonotic transmission. This indicates a probable underreporting of cases, an unknowing regarding the reality of health conditions and the need for more accurate and comprehensive evaluation of sporotrichosis in this region.

Limphocutaneous Sporotrichosis Due to <i>Sporothrix schenckii</i> var <i>schenckii</i>: A Relapsing Case after Treatment with Potassium Iodide in Elderly

Sporotrichosis is a subcutaneous mycosis caused by the Sporothrix schenckii complex. It has three classic clinical variants: fixed, lymphangitic, and systemic. Treatment in most cases has been itraconazole or potassium iodide. The aim of this paper is to communicate an unusual relapsing case treated with IK. We report a 73-year-old woman with lymphangitic sporotrichosis, adequate response to treatment with potassium iodide, and recurrence 15 months after. A molecular test was performed through the amplification of a 331 bp fragment of the calmodulin gene. In both infections, the same specie was isolated. The effects of potassium iodide are briefly discussed, and we conclude that the same treatment can be prescribed, if no side effects are observed.

Clinical Features of Sporotrichosis

Sporotrichosis is a mycosis caused by Sporothrixschenckii complex. Generallyoccurs by traumatic inoculation. It has a wide variety of clinical presentations and can affect the skin, lungs, bones, joints and other organs. The paper reviews the current scientific literature data on sporotrichosisand the different clinical presentations. Results: Sporotrichosis is classified as primary cutaneous disease, with three main clinical presentations: lymphocutaneous, fixed-cutaneous and disseminated; and the systemic disease. The predominant form is lymphangitic sporotrichosis, which represents 60-80% of cases in Mexico.

Species distribution and resistance profile of medical importance bacteria isolated from lesions of cats with sporotrichosis

Sporotrichosis is an infection with zoonotic potential caused by the Sporothrix schenckii complex. It is widely distributed worldwide. The cutaneous form is the most common presentation of the disease. The cat is one of the main animals affected, having numerous fungal cells in its lesions, becoming an important fungi disseminator. Due to the type of skin lesion caused by the fungus, secondary bacterial infections commonly occur. The aim of the present study was to learn about the most common bacterial agents involved in feline lesions with sporotrichosis, as well as their resistance profile to antimicrobial agents. The faster the treatment of bacterial and fungal infections is controlled, the faster the lesions heal. Consequently, the transmission of the disease is controlled. Samples of skin lesions or nasal discharge from 18 domiciled or semi-domiciled cats diagnosed with sporotrichosis were collected. Cats were evaluated for secondary bacterial infections. The samples were processed to isolate aerobic bacteria that were later identified by MALDI TOF. Susceptibility was assessed using the disk diffusion method for a total of 17 antimicrobial agents. The main species identified were Staphylococcus aureus and Staphylococcus felis. Proteus mirabilis has also been identified in some samples. Among these microorganisms, two strains of S. aureus were identified as resistant to methicillin. The TSA's results showed sensitivity to most of the tested antimicrobials. Staphylococcus was the most identified genus in skin lesions and nasal secretions of cats with sporotrichosis. Most microorganisms were sensitive to fluoroquinolones and aminoglycosides. Penicillins and cephalosporins showed less potential for action on these bacteria, which showed greater resistance to these classes.

Synthesis of Hydroxybenzodiazepines with Potential Antioxidant and Antifungal Action

Benzodiazepines derivatives are nitrogen heterocyclic compounds that have various industrial, synthetic, and medicinal applications. Therefore, its potential fully justifies every effort towards the improvement of new, selective, and competent production of these heterocyclic compounds. The novelty of this study encompasses the synthesis of new hydroxylated analogs of 1,5-benzodiazepine together with the evaluation of their biological potential as antioxidants and antifungals candidates. Additionally, the reported antifungal activity against fungi of the Sporothrix schenckii complex inaugurates an unprecedented property for this class of compounds. The results of biological activities assays suggest that the novel 2,7-dimethyl-2,4-bis(4-hydroxyphenyl)-2,3-dihydro1H-1,5-benzodiazepine possesses a high antifungal activity against all fungal strains evaluated of the Sporothrix genus and outstanding total antioxidant capacity. Besides, in silico studies have evidenced that the hydroxylated derivatives have the best aqueous solubility and cell permeability profile, which makes them superior in comparison with the commercial antifungal itraconazole, a drug commonly used in the treatment of sporotrichosis.

Molecular and Biochemical Identification and In Vitro Susceptibility to Itraconazole of Costa Rican Clinical Isolates of the Sporothrix schenckii Complex

Molecular and Biochemical Identification and In Vitro Susceptibility to Itraconazole of Costa Rican Clinical Isolates of the Sporothrix schenckii Complex

Citrus limon, Melaleuca alternifolia E Psidium guajava COMO INIBIDORES NATURAIS DE Sporothrix schenckii

A esporotricose é uma micose subcutânea, decaráter crônico, que pode acometer animais, como cãesegatose em menor frequência os seres humanos. O agente etiológico pertence ao complexoSporothrix schenckii. O tratamento para esta infecção, com os medicamentos atualmente disponíveis, é longo e muitas vezes ineficaz por falta de adesãoàmedicaçãode escolhaou até mesmo por resistência do fungo aos antifúngicos disponíveis. O objetivo deste estudo foi analisar in vitroo potencial do óleo essencial de Citrus limon, do óleo essencial de Melaleuca alternifoliae do extrato da folha de Psidium guajavacomo fármacos naturais para inibição do crescimento de Sporothrix schenckii e por fim comparar a eficácia desses substratos naturaiscom o antifúngico sintético mais utilizado no tratamento da doença, o itraconazol. Os métodos utilizados na pesquisa foram o de disco difusão em ágar e o ensaio da concentração inibitória mínima (CIM). Os testes realizados demonstraram que os óleos essenciais e o extratoestudadoforameficientes parainibir o crescimento fúngico superando até mesmo oitraconazol,utilizado como controle experimental.Os dados obtidos permitem sugerir que os óleos essenciais e o extratotestadospodem ser utilizados como tratamento alternativo ou possivelmente para complementar o tratamento convencional, sendo necessários mais estudos in vivopara confirmar essa afirmação. Os resultados aqui obtidos são relevantespara futuras utilizações desses biofármacos para o tratamento daesporotricose quetemse tornado cada vez mais frequente em felinosem Belo Horizonte e região metropolitana.

Sporothrix brasiliensis on cats with skin ulcers in Southern Brazil.

Sporotrichosis is a disease caused by thermally dimorphic fungi belonging to the Sporothrix schenckii complex. We report the occurrence of multiple cases of sporotrichosis in cats in Porto Alegre (RS), Brazil, from 2015 to 2019. A set of 21 fungal isolates were collected and the partial sequence of calmodulin (CAL) gene compared. All isolates were identified at phenotypic and molecular level as S. brasiliensis. Phylogenetic analysis showed the isolates clustered in two distinct groups, suggesting the presence of multiple genetic variants of S. brasiliensis in the region.

Exogenous fungal quorum sensing molecules inhibit planktonic cell growth and modulate filamentation and biofilm formation in the Sporothrix schenckii complex

This study investigated the effect of the quorum sensing molecules (QSMs) farnesol, 2-phenylehtanol, tyrosol and tryptophol against planktonic cells, filamentation and biofilms of Sporothrix spp. The antifungal activity of QSMs was evaluated by broth microdilution. QSMs showed MICs in the ranges of 0.01-1 µM (farnesol), 1-8 mM (2-phenylehtanol and tyrosol), and >16 mM (tryptophol). Filamentous biofilm formation was inhibited by farnesol and 2-phenylehtanol and stimulated by tyrosol. Yeast biofilm formation was inhibited by 2-phenylehtanol and tyrosol. Tryptophol did not affect Sporothrix biofilm formation. QSMs showed MICs against mature biofilms of 8-32 µM (farnesol), 8-32 mM (2-phenylehtanol) and 64-128 mM (tyrosol). In conclusion, farnesol, 2-phenylethanol and tyrosol have antifungal activity against planktonic and sessile cells and modulate filamentation and biofilm formation in Sporothrix spp.

Canine sporotrichosis: polyphasic taxonomy and antifungal susceptibility profiles of Sporothrix species in an endemic area in Brazil.

Sporotrichosis, a mycosis caused by pathogenic species of the genus Sporothrix, affects diverse species of mammals. Until 2007, Sporothrix schenckii was considered the unique etiologic agent of sporotrichosis. Canine sporotrichosis is a poorly reported disease, and the majority of cases are from Rio de Janeiro, Brazil. There are scarce studies on the characterization of canine isolates of Sporothrix schenckii complex, as well as few antifungal susceptibility data available. The aim of this study was to characterize the clinical isolates of Sporothrix from dogs from Brazil at species level and evaluate their antifungal susceptibility profile. Polyphasic taxonomy was used to characterization at species level (morphological, phenotypical characteristics, and molecular identification). Antifungal susceptibility profiles (amphotericin B, itraconazole, ketoconazole, posaconazole, and terbinafine) were determined using the Clinical and Laboratory Standards Institute broth microdilution method (M38-A2). According to phenotypic identification and molecular analysis, 46 isolates included in this study were identified as S. brasiliensis and one as S. schenckii. Amphotericin B presented the highest minimum inhibitory concentration values, and the other drugs showed effective in vitro antifungal activity. This is the first report of S. schenckii in dogs from Brazil, since S. brasiliensis is the only species that has been described in canine isolates from Rio de Janeiro to date. Nevertheless, no differences were observed in the antifungal susceptibility profiles between the S. brasiliensis and S. schenckii isolates, and it is important to continuously study new canine clinical isolates from Rio de Janeiro, Brazil.

Analysis of biofilm formation by Sporothrix schenckii.

The development of mature biofilms is an aid in numerous aspects of the life cycle of fungi. It is well known that Sporothrix schenckii complex causes a benign subcutaneous mycosis, but recent studies have suggestedthat biofilm formation may be one of the important factors involved in its virulence. Here we report the study of the biomass organization and a model of the stages of S. schenckii biofilm development: adsorption, active adhesion, microcolony formation, maturation, and dispersal of biofilm fragments. During the development, the biofilm is surrounded by extracellular matrix, which contains glycoprotein (mannose rich), carbohydrates, lipids, and nucleic acid. In addition, the extracellular DNA increases in extracellular matrix as a key component to structural integrity and antifungal resistance. The study of S. schenckii biofilm contributes to a better understanding of growth biofilm and physiology, adding new insights into the mechanisms of virulence and persistence of pathogenic microorganisms.

In vitro inhibitory effect of statins on planktonic cells and biofilms of the Sporothrix schenckii species complex.

Introduction. Sporotrichosis, caused by species of the Sporothrix schenckii complex, is the most prevalent subcutaneous mycosis in many areas of Latin America. Statins are a class of drugs widely used for lowering high sterol levels through their action on 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme in the synthesis of sterol.Aim. In this study, the antifungal activity of statins (simvastatin, atorvastatin, pravastatin) against planktonic cells and biofilms of S. schenckii complex species was evaluated, as well as the interaction of pravastatin with classical antifungals (amphotericin B, itraconazole, terbinafine).Methodology. Eighteen strains of Sporothrix species were used. The antifungal susceptibility assay was performed using the broth microdilution method. Mature biofilms were exposed to statins and metabolic activity was measured by the XTT reduction assay.Results. MICs of statins ranged from 8 to 512 μg ml-1 and from 8 to 256 μg ml-1 for filamentous and yeast forms, respectively. Regarding mature biofilms, MICs of 50 % inhibition (SMIC50) were 128 μg ml-1 for simvastatin and atorvastatin and >2048 μg ml-1 for pravastatin. MICs of 90 % inhibition (SMIC90) were 512 μg ml-1 for simvastatin and >2048 μg ml-1 for atorvastatin and pravastatin.Conclusion. These results highlight the antifungal and antibiofilm potential of statins against S. schenckii complex species.