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PloS One 2016Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are...
Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies.
Topics: Antifungal Agents; Humans; Melanins; Naphthalenes; Sporothrix; Sporotrichosis; Terbinafine; Thiazoles
PubMed: 27031728
DOI: 10.1371/journal.pone.0152796 -
PloS One 2020Sporotrichosis is a neglected endemic mycosis with a high incidence in Latin America, mainly in Brazil. Sporothrix schenckii is the most frequent species in Latin...
Sporotrichosis is a neglected endemic mycosis with a high incidence in Latin America, mainly in Brazil. Sporothrix schenckii is the most frequent species in Latin America, whereas Sporothrix brasiliensis is the predominant species observed in Brazil and is associated with both human and animal sporotrichosis. Sporotrichosis treatment remains restricted to a few options, itraconazole being the first choice for human and animal therapy. In this work, we screened the molecular library Pathogen Box (Medicines for Malaria Venture [MMV], Switzerland) in search of compounds with anti-Sporothrix activity. Our initial screen of the 400 compounds identified five compounds that inhibited more than 80% of S. brasiliensis and S. schenkii growth. Among those, three compounds (MMV675968, MMV102872, and MMV002817 (known as iodoquinol)) not previously described as antifungals or agrochemicals, were selected for further evaluation. MMV102872 and iodoquinol showed the most promising combination of antifungal activity (lower inhibitory concentration) and fungal selectivity (lower cytotoxicity in LLC-MK2 cells). Scanning electron microscopy and flow cytometry analyses revealed that MMV102872 and iodoquinol induced changes in cell morphology, membrane integrity, and the presence of neutral lipids, impairing fungal survival. Our results indicate that MMV102872 and iodoquinol are promising molecules for use as scaffolds for the development of new antifungal agents.
Topics: Animals; Antifungal Agents; Cell Line; Drug Discovery; Drug Repositioning; Sporothrix; Sporotrichosis
PubMed: 33052959
DOI: 10.1371/journal.pone.0240658 -
Antimicrobial Agents and Chemotherapy Apr 2020The new complexes Zn(ITZ)Cl (1) and Zn(ITZ)(OH) (2) were synthetized by a reaction of itraconazole with their respective zinc salts under reflux. These Zn-ITZ complexes...
The new complexes Zn(ITZ)Cl (1) and Zn(ITZ)(OH) (2) were synthetized by a reaction of itraconazole with their respective zinc salts under reflux. These Zn-ITZ complexes were characterized by elemental analyses, molar conductivity, mass spectrometry, H and C{H} nuclear magnetic resonance, and UV-vis and infrared spectroscopies. The antiparasitic and antifungal activity of Zn-ITZ complexes was evaluated against three protozoans of medical importance, namely, , , and , and two fungi, namely, and The Zn-ITZ complexes exhibited a broad spectrum of action, with antiparasitic and antifungal activity in low concentrations. The strategy of combining zinc with ITZ was efficient to enhance ITZ activity since Zn-ITZ-complexes were more active than the azole alone. This study opens perspectives for future applications of these Zn-ITZ complexes in the treatment of parasitic diseases and sporotrichosis.
Topics: Antifungal Agents; Antiparasitic Agents; Itraconazole; Leishmania; Leishmania mexicana; Microbial Sensitivity Tests; Parasitic Sensitivity Tests; Sporothrix; Toxoplasma; Trypanosoma cruzi; Zinc
PubMed: 32152072
DOI: 10.1128/AAC.01980-19 -
Frontiers in Microbiology 2021, , and are the main causative agents of sporotrichosis, a human subcutaneous mycosis. Differences in virulence patterns are associated with each species but remain...
, , and are the main causative agents of sporotrichosis, a human subcutaneous mycosis. Differences in virulence patterns are associated with each species but remain largely uncharacterized. The and cell wall composition and virulence are influenced by the culturing media, with little or no influence on . By keeping constant the culturing media, we compared the cell wall composition of three and two strains, previously described as presenting different virulence levels on a murine model of infection. The cell wall composition of the five spp. strains correlated with the biochemical composition of the cell wall previously reported for the species. However, the rhamnose-to-β-glucan ratio exhibits differences among strains, with an increase in cell wall rhamnose-to-β-glucan ratio as their virulence increased. This relationship can be expressed mathematically, which could be an important tool for the determination of virulence in spp. Also, structural differences in rhamnomannan were found, with longer side chains present in strains with lower virulence reported for both species here studied, adding insight to the importance of this polysaccharide in the pathogenic process of these fungi.
PubMed: 34616384
DOI: 10.3389/fmicb.2021.726958 -
Acta Tropica Apr 2022Sporotrichosis is a worldwide zoonosis, prevalent in tropical and subtropical regions. In recent years, there has been a substantial increase in human and feline cases... (Review)
Review
Sporotrichosis is a worldwide zoonosis, prevalent in tropical and subtropical regions. In recent years, there has been a substantial increase in human and feline cases reported in Brazil. Despite this, the antifungal treatment for sporotrichosis is still limited, and thus, research into new therapeutic modalities must be encouraged. Recently, photodynamic therapy has been introduced as a treatment for sporotrichosis. This work presents an overview of both in vitro and in vivo studies that have used photodynamic therapy in the context of photoinactivation of Sporothrix species. Until now, as far as the authors are aware, this is the first scope review specifically on photodynamic therapy for the treatment of sporotrichosis. A systematic electronic search was conducted in two databases: Web of Science and PubMed. Seven original articles published from 2010 to July 2021 were selected, six of which met the proposed inclusion and exclusion criteria and were considered in this scoping review. Concerning the photoinactivation of Sporothrix spp. the results have been promising as studies, in both animals and humans, have reported significant clinical and mycological effects. The most used photosensitizers were methylene blue and its derivatives, and aminolevulinic acid and its methyl derivative, methyl aminolevulinic acid. In conclusion, photodynamic therapy has great potential in treatment of sporotrichosis, as its fungicidal effect both in vitro and in vivo has clearly been demonstrated. Photodynamic therapy could be used in conjunction with classic antifungal agents to optimize treatment outcomes.
Topics: Animals; Antifungal Agents; Brazil; Humans; Photochemotherapy; Sporothrix; Sporotrichosis
PubMed: 35131203
DOI: 10.1016/j.actatropica.2022.106341 -
Journal of Fungi (Basel, Switzerland) Dec 2022Sporotrichosis is a subcutaneous mycosis with worldwide distribution and caused by eight pathogenic species of the genus. Different ex situ preservation methods are...
Sporotrichosis is a subcutaneous mycosis with worldwide distribution and caused by eight pathogenic species of the genus. Different ex situ preservation methods are used around the world to maintain the survival, morphophysiological and genetic traits of fungal strains isolated from patients with sporotrichosis for long terms. The main aim of the present study was to evaluate the survival, phenotypic and genotypic stability of strains after preservation on PDA slant stored at 4 °C, sterile water and cryopreservation at -80 °C, for a period of time of 6, 12, 18 and 24 months of storage. Eight clinical isolates were identified based on a polyphasic approach consisting of classical macro- and micro-morphological traits, biochemical assays, proteomic profiles by MALDI-TOF MS and molecular biology. According to the final identification, one strain was identified as (CMRVS 40428) and seven strains were re-identified as (CMRVS 40421, CMRVS 40423, CMRVS 40424, CMRVS 40425, CMRVS 40426, CMRVS 40427 and CMRVS 40433). In addition, it was observed that the isolates survived after the different time points of storage in distilled water, PDA slant and cryopreservation at -80 °C. For fungi preserved in water, low polymorphisms were detected by the partial sequencing of β-tubulin. Cryopreservation at -80 °C induced morphological changes in one single isolate. The proteomic profiles obtained by MALDI-TOF MS after preservation showed differences among the methods. In conclusion, preservation on agar slant stored at 4 °C was the most effective method to preserve the eight clinical strains. This method produced less change in the phenotypic traits and kept the genetic integrity of all strains. Agar slant stored at 4 °C is a simple and inexpensive method and can be especially used in culture collections of limited funding and resources.
PubMed: 36675855
DOI: 10.3390/jof9010034 -
Brazilian Journal of Microbiology :... Jun 2022Sporotrichosis is a subcutaneous mycosis that affects humans and animals, with few therapeutic options available in the pharmaceutical market. We screened the in vitro...
Sporotrichosis is a subcutaneous mycosis that affects humans and animals, with few therapeutic options available in the pharmaceutical market. We screened the in vitro antifungal activity of fourteen 1,4-naphthoquinones derivative compounds against Sporothrix brasiliensis and Sporothrix schenckii, the main etiological agents of sporotrichosis in Latin America. The most active compound was selected for further studies exploring its antibiofilm activity, effects on yeast morphophysiology, interaction with itraconazole, and selectivity to fungal cells. Among the fourteen 1,4-naphthoquinones tested, naphthoquinone 5, a silver salt of lawsone, was the most active compound. Naphthoquinone 5 was able to inhibit Sporothrix biofilms and induced ROS accumulation, mitochondrial disturbances, and severe plasmatic membrane damage in fungal cells. Furthermore, naphthoquinone 5 was ten times more selective towards fungal cells than fibroblast, and the combination of itraconazole with naphthoquinone 5 improved the inhibitory activity of the azole. Combined, the data presented here indicate that the silver salt naphthoquinone 5 exerts promising in vitro activity against the two main agents of sporotrichosis with important antibiofilm activity and a good toxicity profile, suggesting it is a promising molecule for the development of a new family of antifungals.
Topics: Animals; Antifungal Agents; Biofilms; Itraconazole; Microbial Sensitivity Tests; Naphthoquinones; Silver; Sporothrix; Sporotrichosis
PubMed: 35258797
DOI: 10.1007/s42770-022-00725-1 -
Case Reports in Infectious Diseases 2018is a rare cause of arthritis. Its course is indolent with lack of constitutional symptoms resulting in delayed presentation and diagnosis. It is a dimorphic fungus...
is a rare cause of arthritis. Its course is indolent with lack of constitutional symptoms resulting in delayed presentation and diagnosis. It is a dimorphic fungus found ubiquitously in sphagnum moss, decaying vegetation, soil, and hay. Inoculation of dirt into the skin and soft tissues and, in rare instances, inhalation of aerosolized conidia from soil and plants can lead to infection. Subacute and chronic involvement of skin and subcutaneous tissues is the most common manifestation of sporotrichosis in immunocompetent hosts. In patients with underlying risk factors (HIV, alcoholism, diabetes mellitus, organ transplant patients, immunosuppressive medications, steroids, and malignancies), it can often have disseminated visceral, osteoarticular, meningeal, and pulmonary involvement. Sporothrical arthritis most commonly infects knee joint followed by hand and wrist joints. A culture of is the gold standard for the diagnosis of sporotrichosis. Itraconazole is the drug of choice for osteoarticular sporotrichosis. We present a case of sporotrichal arthritis in a patient without skin or lymph node involvement who underwent treatment with itraconazole resulting in resolution of his symptoms.
PubMed: 30009064
DOI: 10.1155/2018/9037657 -
Frontiers in Pharmacology 2022We designed and synthesized recombinant phage nanofibers displaying ToAP2D peptide and investigated their antifungal effect on and the corresponding mechanism....
We designed and synthesized recombinant phage nanofibers displaying ToAP2D peptide and investigated their antifungal effect on and the corresponding mechanism. Antimicrobial peptide, ToAP2D, was used as the template. The effect of synthesized recombinant phages on the immune function of CD4 T lymphocytes in mice was tested using an enzyme-linked immunosorbent assay. The therapeutic effect and safety of recombinant phage administration on -infected BALB/c mice were evaluated based on survival analysis, histopathological changes, and renal and liver functions. The successfully prepared recombinant phage displaying ToAP2D peptides significantly inhibited growth. According to the scanning electron microscopy results, the recombinant phage caused shrinkage and rupture of , leading to leakage of the contents. The Hoechst/propidium iodide double staining test indicated that the recombinant phage could induce cell apoptosis of . The apoptotic pathway might be due to the accumulation of reactive oxygen species in large quantities in cells, activating caspase dependence; this reduced inflammation, prolonged the survival time, and enhanced levels of IFN-γ and IL-17 in mice. We believe that recombinant phage inhibits growth by adjusting the immune response of mice, inducing apoptosis and improving animal survival. This study offers a new approach to preparing antimicrobial peptides.
PubMed: 36278206
DOI: 10.3389/fphar.2022.1022651 -
Medical Mycology Journal 2017Feline sporotrichosis has been reported in Malaysia since the 1990's. Since then, studies have revealed that clinical clade D, Sporothrix schenckii sensu stricto, of a... (Review)
Review
Feline sporotrichosis has been reported in Malaysia since the 1990's. Since then, studies have revealed that clinical clade D, Sporothrix schenckii sensu stricto, of a single clonal strain is the most common cause of this disease in Malaysia. The prevalence of a single clonal strain from a clinical clade was never before reported in Asia in a specific geographical niche. This raises the possibility of a process of purifying selection and subsequent clonal proliferation. While agricultural practices may serve as the selective pressure, direct causality has yet to be established. Studies into the thermo-tolerability of the Malaysian clonal strain of S. schenckii sensu stricto revealed that a small minority of clinical isolates have the capacity to grow at 37℃, while the majority displayed low susceptibility to commonly used antifungals in clinical practice, such as itraconazole (ITZ) and terbinafine (TRB). Despite unestablished breakpoints, suspected resistance (MIC > 4 mg/mL) towards amphotericin B (AMB) and fluconazole (FLC) was recorded in the isolates. This explains the often lack of clinical response in feline patients treated with recommended doses of antifungals, including ITZ. Coupled with the potential zoonotic transmission to clients and veterinarians, protracted treatment period, and subsequent cost of treatment, prognosis of feline sporotrichosis is often regarded to be poor. The use of a higher dose of ITZ has been reported, and an adoption of this high-dose treatment regime is reported in this manuscript, with complete cure achieved in cases of recalcitrant and/or unresponsive feline sporotrichosis, which would otherwise be euthanized.
Topics: Amphotericin B; Animals; Antifungal Agents; Cat Diseases; Cats; Drug Resistance, Fungal; Fluconazole; Humans; Itraconazole; Malaysia; Naphthalenes; Prevalence; Sporothrix; Sporotrichosis; Terbinafine; Zoonoses
PubMed: 28855477
DOI: 10.3314/mmj.17.014