Potassium iodide and miltefosine inhibit biofilms of Sporothrix schenckii species complex in yeast and filamentous forms

Brilhante, Raimunda Sâmia Nogueira; Silva, Maria Lucilene Queiroz da; Pereira, Vandbergue Santos; Oliveira, Jonathas Sales de; Maciel, Juliana Maria; Silva, Isaac Neto Góes da; Garcia, Lana Glerieide Silva; Guedes, Gláucia Morgana de Melo; Cordeiro, Rossana de Aguiar; Pereira-Neto, Waldemiro de Aquino; Camargo, Zoilo Pires de; Rodrigues, Anderson Messias; Sidrim, José Júlio Costa; Castelo-Branco, Débora de Souza Collares Maia; Rocha, Marcos Fábio Gadelha

doi:10.1093/mmy/myy119

Cited by 27 publications

(18 citation statements)

References 35 publications

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“…Potassium iodide is also recommended for the treatment of cat cases refractory to itraconazole (in those presenting nasal mucosal lesions and respiratory signs) [235]. The precise mechanism by which potassium iodide acts is still unknown [236], although Brilhante et al [237] recently reported the efficacy of this drug in inhibiting biofilm formation of Sporothrix cells, grown in the planktonic state and mature biofilms in both filamentous and yeast forms. Itraconazole is the drug of choice for treatment in humans (100-200 mg/day orally) and cats (8.3-27.7 mg/kg/day) [151,166,238], but other azoles (e.g., posaconazole) as well as other antifungal classes, such as allylamine (terbinafine) and polyene (amphotericin B), may be employed depending on the clinical factors and condition of the patient's immune system.…”

Section: Therapymentioning

confidence: 99%

The threat of emerging and re-emerging pathogenic Sporothrix species

et al. 2020

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Sporotrichosis is a neglected subcutaneous mycosis of humans and animals acquired by traumatic inoculation of soil and plant material (classical route) contaminated with infectious propagules of the pathogen or being bitten/scratched by infected cats (alternative route). Within a genus composed of 53 species displaying an essentially environmental core, there are only a few members which have considerable impacts on human or animal health. Infections are typically caused by S. brasiliensis, S. schenckii or S. globosa. Rare mammal pathogens include members of the S. pallida and S. stenocereus complexes. To illustrate the tremendous impact of emerging zoonotic sporotrichosis on public health, we discuss the main features of the expanding epidemics driven by S. brasiliensis in cats and humans. The cat entry in the transmission chain of sporotrichosis, causing epizooties (cat-cat) or zoonosis (cat-human), has contributed to the definition of new paradigms in Sporothrix transmission, reaching epidemic levels, making the disease a serious public health problem. Indeed, S. brasiliensis infection in humans and animals is likely to become even more important in the future, with projections of its expansion in biogeographic domains and host range, as well as greater virulence in mammals. Therefore, lessons from a long-standing outbreak in the state of Rio de Janeiro about the source and distribution of the etiological agents among outbreak areas can be used to create better control and prevention plans and increase awareness of sporotrichosis as a serious emerging zoonotic disease. Keywords Sporothrix Á Sporotrichosis Á Emerging zoonoses Á Control and prevention Á Preparedness and biodefense Á Pathogenicity Á Virulence Á Sporothrix brasiliensis Á Neglected tropical diseases The story behind the Sporothrix species pathogenic to mammals Sporotrichosis is a fungal disease caused by the infection of Sporothrix spp. It usually affects the skin Handling editor: Ferry Hagen.

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Section: Therapymentioning

confidence: 99%

The threat of emerging and re-emerging pathogenic Sporothrix species

et al. 2020

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“…MIC, minimum inhibitory concentration. and 10-50× MIC (40-200 µg/ml), respectively (Vila et al, 2013;Brilhante et al, 2019). Interestingly, Scedosporium and Lomentospora preformed biofilms were affected in the presence of 4× and 8× MIC of miltefosine, which represents 16 and 32 µg/ ml, respectively, indicating that it could be more susceptible compared with other pathogenic fungi.…”

Section: Discussionmentioning

confidence: 99%

Miltefosine Against Scedosporium and Lomentospora Species: Antifungal Activity and Its Effects on Fungal Cells

Rollin-Pinheiro

Almeida

Rochetti

et al. 2021

Front. Cell. Infect. Microbiol.

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Scedosporium and Lomentospora species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising conditions. Because they are usually resistant to many antifungal drugs available in clinical settings, studies of alternative targets in fungal cells and therapeutic approaches are necessary. In the present work, we evaluated the in vitro antifungal activity of miltefosine against Scedosporium and Lomentospora species and how this phospholipid analogue affects the fungal cell. Miltefosine inhibited different Scedosporium and Lomentospora species at 2–4 µg/ml and reduced biofilm formation. The loss of membrane integrity in Scedosporium aurantiacum caused by miltefosine was demonstrated by leakage of intracellular components and lipid raft disorganisation. The exogenous addition of glucosylceramide decreased the inhibitory activity of miltefosine. Reactive oxygen species production and mitochondrial activity were also affected by miltefosine, as well as the susceptibility to fluconazole, caspofungin and myoricin. The data obtained in the present study contribute to clarify the dynamics of the interaction between miltefosine and Scedosporium and Lomentospora cells, highlighting its potential use as new antifungal drug in the future.

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“…The SMIC50 values were higher than the MICs of planktonic susceptibility, demonstrating the increased tolerance of biofilms to these drugs. Despite forming biofilms in both forms, biofilms of filamentous forms are more complex and have more layers than yeast biofilms of Sporothix species [6]. In addition, the filamentous form is responsible for maintaining the biological cycle of dissemination of this fungus, so the effect of statins on this form of growth was evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…In order to establish themselves in the host organism, fungi have several virulence factors, including the ability to form biofilms, which are composed of cells that form microcolonies attached to a substrate recognized by the extracellular matrix, which allows or detects whether the microorganism is in a hostile or protected environment regarding host immune defence [3][4][5]. Among the virulence factors that contribute to the survival of S. schenckii complex species, biofilm formation has been described for both filamentous and yeast forms [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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

Brilhante

Fonseca

Pereira

et al. 2020

Journal of Medical Microbiology

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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.

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Potassium iodide and miltefosine inhibit biofilms of Sporothrix schenckii species complex in yeast and filamentous forms

Cited by 27 publications

References 35 publications

The threat of emerging and re-emerging pathogenic Sporothrix species

The threat of emerging and re-emerging pathogenic Sporothrix species

Miltefosine Against Scedosporium and Lomentospora Species: Antifungal Activity and Its Effects on Fungal Cells

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

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