Genetic diversity and antifungal susceptibility profiles in causative agents of sporotrichosis

Rodrigues, Anderson Messias; Hoog, G.S. de; Pires, Débora de Cássia; Brihante, Raimunda Sâmia Nogueira; Sidrim, José Júlio da Costa; Gadelha, Marcos Fabio; Colombo, Arnaldo Lopes; Camargo, Zoilo Pires de

doi:10.1186/1471-2334-14-219

Cited by 121 publications

(129 citation statements)

References 52 publications

(122 reference statements)

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“…However, recent reports demonstrated that these drugs are less potent against S. brasiliensis isolates, which have high minimum inhibitory concentration (MIC) values in vitro for these antifungals (Ottonelli Stopiglia et al, 2014;Rodrigues et al, 2014;Borba-Santos et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Miltefosine is active against Sporothrix brasiliensis isolates with in vitro low susceptibility to amphotericin B or itraconazole

Borba-Santos

Gagini

Ishida

et al. 2015

Journal of Medical Microbiology

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Sporotrichosis is a common mycosis caused by dimorphic fungi from the Sporothrix schenckii complex. In recent years, sporotrichosis incidence rates have increased in the Brazilian state of Rio de Janeiro, where Sporothrix brasiliensis is the species more frequently isolated from patients. The standard antifungals itraconazole and amphotericin B are recommended as first-line therapy for cutaneous/lymphocutaneous and disseminated sporotrichosis, respectively, although decreased sensitivity to these drugs in vitro was reported for clinical isolates of S. brasiliensis. Here, we evaluated the activity of the phospholipid analogue miltefosine -already in clinical use against leishmaniasis -towards the pathogenic yeast form of S. brasiliensis isolates with low sensitivity to itraconazole or amphotericin B in vitro. Miltefosine had fungicidal activity, with minimum inhibitory concentration (MIC) values of 1-2 mg ml "1 . Miltefosine exposure led to loss of plasma membrane integrity, and transmission electron microscopy (TEM) analysis revealed a decrease in cytoplasmic electron density, alterations in the thickness of cell wall layers and accumulation of an electron-dense material in the cell wall. Flow cytometry analysis using an antimelanin antibody revealed an increase in cell wall melanin in yeasts treated with miltefosine, when compared with control cells. The cytotoxicity of miltefosine was comparable to those of amphotericin B, but miltefosine showed a higher selectivity index towards the fungus. Our results suggest that miltefosine could be an effective alternative for the treatment of S. brasiliensis sporotrichosis, when standard treatment fails. Nevertheless, in vivo studies are required to confirm the antifungal potential of miltefosine for the treatment of sporotrichosis. INTRODUCTIONSporotrichosis is the most frequent subcutaneous mycosis in Latin America, and has high incidence rates in Brazil, especially in the Rio de Janeiro state, where zoonotic transmission prevails (Barros et al., 2010). This disease is caused by dimorphic fungal species from the Sporothrix schenckii complex (Marimon et al., 2007;, including Sporothrix brasiliensis, the most virulent species (ArrillagaMoncrieff et al., 2009;Fernandes et al., 2013) and the most prevalent in the clinical cases from the Rio de Janeiro state (Oliveira et al., 2011;Rodrigues et al., 2013a;Borba-Santos et al., 2014). In zoonotic transmission, sporotrichosis is mainly acquired by scratches, bites or direct contact with lesion secretion from contaminated animals, where yeasts are the infective forms (Rodrigues et al., 2013b).The 'gold standard' treatment for cutaneous and lymphocutaneous forms of sporotrichosis is itraconazole, while amphotericin B is the first-line drug of choice for disseminated forms of the disease (Kauffman et al., 2007). However, recent reports demonstrated that these drugs are less potent against S. brasiliensis isolates, which have high minimum inhibitory concentration (MIC) values in vitro for these antifungals (Ottonelli Stopiglia et a...

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Section: Introductionmentioning

confidence: 99%

Miltefosine is active against Sporothrix brasiliensis isolates with in vitro low susceptibility to amphotericin B or itraconazole

Borba-Santos

Gagini

Ishida

et al. 2015

Journal of Medical Microbiology

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“…In most of these cases, morphological correlates of phylogenetic species were not observed until it was possible to sort strains into the various cryptic species, only then were the phenotypic differences recognized. For example, with Sporothrix species, after phylogenetic species and populations had been identified, tests of antifungal drug susceptibility found associations between genotype and phenotype that could be used to predict therapeutic outcomes (Rodrigues et al 2014).…”

Section: Population Geneticsmentioning

confidence: 99%

Evolutionary Perspectives on Human Fungal Pathogens

Taylor

2014

Cold Spring Harb Perspect Med

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“…Four species of the Sporothrix complex have been reported as causal agents of sporotrichosis: S. brasiliensis, S. globosa, S. schenckii s. str., and S. schenckii luriei (Rodrigues et al, 2014). S. pallida and S. mexicana are mainly environmental but may also be potentially pathogenic to humans and other mammals.…”

Section: Introductionmentioning

confidence: 99%

Morphological and physiological comparison of taxa comprising the Sporothrix schenckii complex

Zhao

Zhou

et al. 2015

J. Zhejiang Univ. Sci. B

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Based on recent molecular data, it has been suggested that Sporothrix globosa is the main causal agent of sporotrichosis in China. The objective of this study was to compare the morphology, growth characteristics, patterns of carbon source usage, and susceptibility to antifungal agents among Sporothrix strains. A total of 15 clinical strains confirmed to be S. globosa, from three different regions of China, and 11 ex-type strains from the CBS-KNAW biodiversity center were obtained. The elongated conidia of S. pallida, S. variecibatus, S. schenckii, and S. schenckii luriei were clearly different from the subglobose and globose conidia of S. globosa strains. S. schenckii is able to assimilate sucrose, raffinose, and ribitol. Susceptibility profiles of these Sporothrix species were evaluated by measuring minimum inhibitory concentrations (MICs). Fluconazole, itraconazole, terbinafine, and amphotericin B showed good activity against most S. globosa clinical isolates from China. Potassium iodide also showed a low MIC against S. pallida, while fluconazole showed a high MIC for S. mexicana, S. humicola, S. globosa, S. schenckii, and S. inflata; these strains might be considered tolerant. The species showed differences in susceptibility to antifungal drugs and should therefore be properly identified during diagnosis prior to designing therapeutic strategies.

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Genetic diversity and antifungal susceptibility profiles in causative agents of sporotrichosis

Cited by 121 publications

References 52 publications

Miltefosine is active against Sporothrix brasiliensis isolates with in vitro low susceptibility to amphotericin B or itraconazole

Miltefosine is active against Sporothrix brasiliensis isolates with in vitro low susceptibility to amphotericin B or itraconazole

Evolutionary Perspectives on Human Fungal Pathogens

Morphological and physiological comparison of taxa comprising the Sporothrix schenckii complex

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