Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine

Almeida‐Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito‐Santos, Fabio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancopé‐Oliveira, Rosely Maria

doi:10.1371/journal.pone.0152796

Cited by 60 publications

(31 citation statements)

References 41 publications

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“…This should be especially addressed when it comes to S. brasiliensis, the main species identified in the Rio de Janeiro epidemic and described as being highly virulent. In fact, virulent factors such as melanin production may compromise terbinafine's interaction with the fungal wall, leading to an impairment in its antifungal ability [60]. Having said that, we strongly suggest that some light be shed on these key factors, and that they should be carefully interpreted while evaluating new regimens of treatment for sporotrichosis.…”

Section: Discussionmentioning

confidence: 93%

Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review

Viana¹,

Figueiredo²,

Gremião³

et al. 2017

Mycopathologia

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Sporotrichosis occurs worldwide, and the metropolitan region of Rio de Janeiro, Brazil, is a main endemic area, with a large number of human and animal cases in the last 19 years. This mycosis is more frequently described in cats rather than in dogs. There are a limited number of oral antifungal agents for the treatment of sporotrichosis in animals. In this context, the effectiveness of terbinafine in the treatment of sporotrichosis in humans, as well as the promising results of in vitro susceptibility tests, inspired us to use this drug in the therapy of this mycosis in dogs. We reported for the first time the use of terbinafine in the treatment of two dogs with sporotrichosis caused by Sporothrix brasiliensis. Moreover, we provided an overview of therapeutic features of canine sporotrichosis cases reported since the 1960s. One of the dogs presented the fixed cutaneous form of the disease, while the other patient presented hyperemia of the nasal mucosa and respiratory signs only. Terbinafine showed high antifungal activity in vitro against the canine Sporothrix isolates. The dogs were successfully treated with terbinafine, with remission of all clinical signs initially presented. The current reports indicate that this drug can emerge as a therapeutic option for canine sporotrichosis.

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Section: Discussionmentioning

confidence: 93%

Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review

Viana¹,

Figueiredo²,

Gremião³

et al. 2017

Mycopathologia

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“…Melanin is a virulence factor that enhances fungal resistance to environmental stressors and immune responses in the host (Eisenman and Casadevall 2012). The natural presence of melanin has been demonstrated in S. schenckii species and it favors the fungal virulence and resistance to antifungal drugs (Morris-Jones et al ., 2003; Madrid et al ., 2011; Almeida-Paes et al ., 2016). Here, increased production of cytoplasmic melanosomes in different phases of formation was observed in conidia of fungi exposed to toluene, especially at the highest concentration.…”

Section: Resultsmentioning

confidence: 99%

Adaptive stress response induced by toluene increasesSporothrix schenckiivirulence and host immune response

Téllez-Martínez

Batista-Duharte

Silva

et al. 2019

Preprint

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24Environmental factors modify the physiology of microorganisms, allowing their survival in 25 extreme conditions. However, the influence of chemical contaminants on fungal virulence has 26 been little studied. Sporotrichosis is an emergent fungal disease caused by Sporothrix schenckii, 27 a soil-inhabiting fungus that has been found in polluted environments. Here, we evaluated the 28 adaptive stress response of S. schenckii induced by toluene, a key soil contaminant. The effect 29 on fungal virulence and host immune response was also assessed. The fungus survived up to 30 0.10% toluene in liquid medium. Greater production of melanosomes and enhanced activity 31 superoxide dismutase, associated to increased tolerance to H2O2 were observed in toluene-32 exposed fungi. Intraperitoneal infection of mice with S. schenckii treated with either 0, 0.01 or 33 0.1% of toluene, resulted in greater fungal burden at day 7 post-infection in spleen and liver in 34 the groups infected with fungus treated with toluene 0.1%. A higher production of Il-1β, TNF-35 α, IL-10 and nitric oxyde by peritoneal macrophages and IFNɣ, IL-4 and IL-17 by splenocytes 36 was also observed in that group. Our findings showed that morphological and functional 37 changes induced by toluene leads to increased S. schenckii virulence and antifungal host 38 immune response in our model. 39 40 41 42 43 44 45 78 Aromatic compounds such as benzene, toluene, ethylbenzene and xylene isomers, 79 collectively known as BTEX, are one of the major contributors to environmental pollution. 80 BTEX are extensively used as solvents in many industrial processes and as base reagents for 81 the production of chemicals products. In addition, BTEX are components of gasoline and 82 aviation fuels. They are often released in the environment during production, transport, use and 83 disposal, causing groundwater, surface water, and soil contamination. Toluene has been found 84 in at least 1,012 of the 1,699 National Priorities List sites identified by the Environmental 85 Protection Agency (EPA) and it is included in the Agency for Toxic Substances and Disease 86 Registry (ATSDR) 2017 substance priority list, which is based on a combination of their 87 frequency, toxicity, and potential for human exposure (Agency for Toxic Substances and 88 Disease Registry. ATSDR's Substance Priority List. 2017).89Prenafreta-Boldu isolated several fungi, including S. schenckii, in biofilters exposed to 90 polluted air or hydrocarbon gas streams. The data from this research showed that volatile 91 hydrocarbon-degrading strains are closely related to a very restricted number of pathogenic 92 fungal species that cause severe mycoses, especially neurological infections, in 93 immunocompetent individuals (Prenafeta-Boldú et al., 2006). 94To date, there have been no studies examining the influence of chemical contaminants 95 on the biology of S. schenckii sensu latu. Given that this fungus inhabits soils and this niche is 96 frequently contaminated with oil and their products, the objective of this...

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“…In Aspergillus fumigatus , the production of pyomelanin was shown to be upregulated during infection but dispensable for virulence (Heinekamp et al, 2012 ). In the fungal pathogen Sporothrix brasiliensis pyomelanin was shown to protect this fungal pathogen against antifungal drugs (Almeida-Paes et al, 2016 ). Further melanin and genes involved in melanin production were shown to be crucial for iron uptake (Ding et al, 2014 ) in Cryptococcus neoformans .…”

Section: Discussionmentioning

confidence: 99%

The Transcriptome of Exophiala dermatitidis during Ex-vivo Skin Model Infection

Poyntner

Blasi

Arcalís

et al. 2016

Front. Cell. Infect. Microbiol.

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The black yeast Exophiala dermatitidis is a widespread polyextremophile and human pathogen, that is found in extreme natural habitats and man-made environments such as dishwashers. It can cause various diseases ranging from phaeohyphomycosis and systemic infections, with fatality rates reaching 40%. While the number of cases in immunocompromised patients are increasing, knowledge of the infections, virulence factors and host response is still scarce. In this study, for the first time, an artificial infection of an ex-vivo skin model with Exophiala dermatitidis was monitored microscopically and transcriptomically. Results show that Exophiala dermatitidis is able to actively grow and penetrate the skin. The analysis of the genomic and RNA-sequencing data delivers a rich and complex transcriptome where circular RNAs, fusion transcripts, long non-coding RNAs and antisense transcripts are found. Changes in transcription strongly affect pathways related to nutrients acquisition, energy metabolism, cell wall, morphological switch, and known virulence factors. The L-Tyrosine melanin pathway is specifically upregulated during infection. Moreover the production of secondary metabolites, especially alkaloids, is increased. Our study is the first that gives an insight into the complexity of the transcriptome of Exophiala dermatitidis during artificial skin infections and reveals new virulence factors.

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Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine

Cited by 60 publications

References 41 publications

Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review

Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review

Adaptive stress response induced by toluene increasesSporothrix schenckiivirulence and host immune response

The Transcriptome of Exophiala dermatitidis during Ex-vivo Skin Model Infection

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