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[PMID]: 28989052 [Au] Autor: Matowane RG; Wieteska L; Bamal HD; Kgosiemang IKR; Van Wyk M; Manume NA; Abdalla SMH; Mashele SS; Gront D; Syed K [Ad] Endereço: Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa. [Ti] Título: In silico analysis of cytochrome P450 monooxygenases in chronic granulomatous infectious fungus Sporothrix schenckii: Special focus on CYP51. [So] Source: Biochim Biophys Acta;1866(1):166-177, 2018 01. [Is] ISSN: 0006-3002 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Sporotrichosis is an emerging chronic, granulomatous, subcutaneous, mycotic infection caused by Sporothrix species. Sporotrichosis is treated with the azole drug itraconazole as ketoconazole is ineffective. It is a well-known fact that azole drugs act by inhibiting cytochrome P450 monooxygenases (P450s), heme-thiolate proteins. To date, nothing is known about P450s in Sporothrix schenckii and the molecular basis of its resistance to ketoconazole. Here we present genome-wide identification, annotation, phylogenetic analysis and comprehensive P450 family-level comparative analysis of S. schenckii P450s with pathogenic fungi P450s, along with a rationale for ketoconazole resistance by S. schenckii based on in silico structural analysis of CYP51. Genome data-mining of S. schenckii revealed 40 P450s in its genome that can be grouped into 32 P450 families and 39 P450 subfamilies. Comprehensive comparative analysis of P450s revealed that S. schenckii shares 11 P450 families with plant pathogenic fungi and has three unique P450 families: CYP5077, CYP5386 and CYP5696 (novel family). Among P450s, CYP51, the main target of azole drugs was also found in S. schenckii. 3D modeling of S. schenckii CYP51 revealed the presence of characteristic P450 motifs with exceptionally large reductase interaction site 2. In silico analysis revealed number of mutations that can be associated with ketoconazole resistance, especially at the channel entrance to the active site. One of possible reason for better stabilization of itraconazole, compared to ketoconazole, is that the more extended molecule of itraconazole may form a hydrogen bond with ASN-230. This in turn may explain its effectiveness against S. schenckii vis-a-vis resistant to ketoconazole. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone. [Mh] Termos MeSH primário: Antifúngicos/química Sistema Enzimático do Citocromo P-450/química Proteínas Fúngicas/química Genoma Fúngico Itraconazol/química Sporothrix/enzimologia [Mh] Termos MeSH secundário: Sequência de Aminoácidos Animais Antifúngicos/farmacologia Domínio Catalítico Cristalografia por Raios X Sistema Enzimático do Citocromo P-450/genética Sistema Enzimático do Citocromo P-450/metabolismo Farmacorresistência Fúngica/genética Proteínas Fúngicas/antagonistas & inibidores Proteínas Fúngicas/genética Proteínas Fúngicas/metabolismo Expressão Gênica Seres Humanos Itraconazol/farmacologia Cetoconazol/química Cetoconazol/farmacologia Simulação de Acoplamento Molecular Família Multigênica Filogenia Plantas/microbiologia Ligação Proteica Domínios e Motivos de Interação entre Proteínas Estrutura Secundária de Proteína Alinhamento de Sequência Sporothrix/classificação Sporothrix/efeitos dos fármacos Sporothrix/genética Esporotricose/tratamento farmacológico Esporotricose/microbiologia Homologia Estrutural de Proteína [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Antifungal Agents); 0 (Fungal Proteins); 304NUG5GF4 (Itraconazole); 9035-51-2 (Cytochrome P-450 Enzyme System); R9400W927I (Ketoconazole) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180208 [Lr] Data última revisão: 180208 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171010 [St] Status: MEDLINE

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[PMID]: 29211110 [Au] Autor: Cruz ILR; Figueiredo-Carvalho MHG; Zancopé-Oliveira RM; Almeida-Paes R [Ad] Endereço: Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Micologia, Rio de Janeiro, RJ, Brasil. [Ti] Título: Evaluation of melanin production by Sporothrix luriei. [So] Source: Mem Inst Oswaldo Cruz;113(1):68-70, 2018 Jan. [Is] ISSN: 1678-8060 [Cp] País de publicação: Brazil [La] Idioma: eng [Ab] Resumo: There is a paucity of studies on the cell biology of Sporothrix luriei, the less common of the pathogenic Sporothrix species worldwide. The production of DHN-melanin, eumelanin, and pyomelanin were evaluated on the mycelial and yeast forms of the S. luriei ATCC 18616 strain. The mycelial form of this species produced only pyomelanin, which protected the fungus against environmental stressors such as ultraviolet light, heat, and cold. The yeast form was unable to produce any of the tested melanin types. The lack of melanin in the parasitic form of S. luriei may be an explanation for its low frequency in human infections. [Mh] Termos MeSH primário: Melaninas/biossíntese Sporothrix/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Melanins); 0 (pyomelanin); 12627-86-0 (eumelanin) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180131 [Lr] Data última revisão: 180131 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171207 [St] Status: MEDLINE

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[PMID]: 28854184 [Au] Autor: Della Terra PP; Rodrigues AM; Fernandes GF; Nishikaku AS; Burger E; de Camargo ZP [Ad] Endereço: Department of Medicine, Discipline of Infectious Diseases, Federal University of São Paulo (UNIFESP), São Paulo, Brazil. [Ti] Título: Exploring virulence and immunogenicity in the emerging pathogen Sporothrix brasiliensis. [So] Source: PLoS Negl Trop Dis;11(8):e0005903, 2017 Aug. [Is] ISSN: 1935-2735 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Sporotrichosis is a polymorphic chronic infection of humans and animals classically acquired after traumatic inoculation with soil and plant material contaminated with Sporothrix spp. propagules. An alternative and successful route of transmission is bites and scratches from diseased cats, through which Sporothrix yeasts are inoculated into mammalian tissue. The development of a murine model of subcutaneous sporotrichosis mimicking the alternative route of transmission is essential to understanding disease pathogenesis and the development of novel therapeutic strategies. To explore the impact of horizontal transmission in animals (e.g., cat-cat) and zoonotic transmission on Sporothrix fitness, the left hind footpads of BALB/c mice were inoculated with 5×106 yeasts (n = 11 S. brasiliensis, n = 2 S. schenckii, or n = 1 S. globosa). Twenty days post-infection, our model reproduced both the pathophysiology and symptomology of sporotrichosis with suppurating subcutaneous nodules that progressed proximally along lymphatic channels. Across the main pathogenic members of the S. schenckii clade, S. brasiliensis was usually more virulent than S. schenckii and S. globosa. However, the virulence in S. brasiliensis was strain-dependent, and we demonstrated that highly virulent isolates disseminate from the left hind footpad to the liver, spleen, kidneys, lungs, heart, and brain of infected animals, inducing significant and chronic weight loss (losing up to 15% of their body weight). The weight loss correlated with host death between 2 and 16 weeks post-infection. Histopathological features included necrosis, suppurative inflammation, and polymorphonuclear and mononuclear inflammatory infiltrates. Immunoblot using specific antisera and homologous exoantigen investigated the humoral response. Antigenic profiles were isolate-specific, supporting the hypothesis that different Sporothrix species can elicit a heterogeneous humoral response over time, but cross reaction was observed between S. brasiliensis and S. schenckii proteomes. Despite great diversity in the immunoblot profiles, antibodies were mainly derived against 3-carboxymuconate cyclase, a glycoprotein oscillating between 60 and 70 kDa (gp60-gp70) and a 100-kDa molecule in nearly 100% of the assays. Thus, our data broaden the current view of virulence and immunogenicity in the Sporothrix-sporotrichosis system, substantially expanding the possibilities for comparative genomic with isolates bearing divergent virulence traits and helping uncover the molecular mechanisms and evolutionary pressures underpinning the emergence of Sporothrix virulence. [Mh] Termos MeSH primário: Sporothrix/imunologia Sporothrix/patogenicidade Esporotricose/imunologia Esporotricose/patologia [Mh] Termos MeSH secundário: Estruturas Animais/microbiologia Estruturas Animais/patologia Animais Anticorpos Antifúngicos/sangue Antígenos de Fungos/imunologia Peso Corporal Modelos Animais de Doenças Histocitoquímica Immunoblotting Camundongos Endogâmicos BALB C Análise de Sobrevida Fatores de Tempo Virulência [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Fungal); 0 (Antigens, Fungal) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170917 [Lr] Data última revisão: 170917 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170831 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pntd.0005903

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[PMID]: 28699881 [Au] Autor: Waller SB; Madrid IM; Hoffmann JF; Picoli T; Cleff MB; Chaves FC; Faria RO; Meireles MCA; Braga de Mello JR [Ad] Endereço: 1​Department of Preventive Veterinary, College of Veterinary, Federal University of Pelotas, Pelotas/RS, Brazil. [Ti] Título: Chemical composition and cytotoxicity of extracts of marjoram and rosemary and their activity against Sporothrix brasiliensis. [So] Source: J Med Microbiol;66(7):1076-1083, 2017 Jul. [Is] ISSN: 1473-5644 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: PURPOSE: Motivated by increasing reports of antifungal resistance in human and animal sporotrichosis, this study evaluated the chemical composition, cytotoxicity and anti-Sporothrix brasiliensis activity of extracts of marjoram (Origanum majorana) and rosemary (Rosmarinus officinalis). METHODOLOGY: Ten (INF10) and 60 min (INF60) infusions, a decoction and a hydroalcoholic extract (HAE, 70 %) were prepared from both plants (10 % w/v). The extract composition was analysed by liquid chromatography/mass spectrometry and the cytotoxicity was evaluated using a colorimetric assay in canine and feline kidney cells. Using a broth microdilution assay (CLSI M38-A2) adapted to the extracts, 30 Sporothrix brasiliensis isolates from dogs, cats and humans, and one Sporothrix schenckii were tested.Results/Key findings. The predominant phenolic compounds found in all extracts were 4-hydroxybenzoic acid, caffeic acid and chlorogenic acid. Luteolin was also one of the predominant compounds, but only in the HAE of marjoram. Extracts of marjoram maintained cell viability in concentrations up to 2.5 mg ml-1 for the feline cell line and up to 10 mg ml-1 for the canine cell line, whereas in rosemary, the cell viability for both kidney lines was maintained with concentrations up to 5 mg ml-1. The activity of rosemary extracts was low or absent. Among the marjoram extracts, HAE was highlighted and had fungistatic activity against Sporothrix brasiliensis (MIC5040 mg ml-1), including in all itraconazole-resistant isolates. S. schenckiisensu stricto was sensitive to marjoram extracts (MIC/MFC ≤5 mg ml-1), with the exception of INF10. CONCLUSION: These findings support the potential usefulness of the HAE of marjoram in the treatment of sporotrichosis. [Mh] Termos MeSH primário: Antifúngicos/farmacologia Origanum/química Compostos Fitoquímicos/farmacologia Extratos Vegetais/farmacologia Rosmarinus/química Sporothrix/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Antifúngicos/isolamento & purificação Antifúngicos/toxicidade Gatos Linhagem Celular Sobrevivência Celular/efeitos dos fármacos Cromatografia Líquida Cães Espectrometria de Massas Testes de Sensibilidade Microbiana Compostos Fitoquímicos/isolamento & purificação Compostos Fitoquímicos/toxicidade Extratos Vegetais/isolamento & purificação Extratos Vegetais/toxicidade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antifungal Agents); 0 (Phytochemicals); 0 (Plant Extracts) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170809 [Lr] Data última revisão: 170809 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170713 [St] Status: MEDLINE [do] DOI: 10.1099/jmm.0.000517

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[PMID]: 28502945 [Au] Autor: Shimizu T; Akita S; Harada Y; Oguro E; Okita Y; Shigesaka M; Matsuoka H; Nii T; Teshigawara S; Kudo-Tanaka E; Tsuji S; Matsushita M; Ohshima S; Hoshida Y; Hashimoto J; Saeki Y [Ad] Endereço: Department of Rheumatology and Allergology, Osaka Minami Medical Center, Japan. [Ti] Título: Sporotrichal Tenosynovitis Diagnosed Helpfully by Musculoskeletal Ultrasonography. [So] Source: Intern Med;56(10):1243-1246, 2017. [Is] ISSN: 1349-7235 [Cp] País de publicação: Japan [La] Idioma: eng [Ab] Resumo: A 72-year-old man presented with persistent oligoarthritis and positive results for rheumatoid factor and was suspected of having rheumatoid arthritis (RA). However, the musculoskeletal ultrasonography (MSUS) findings were not consistent with those of typical RA. He had undergone surgery for carpal tunnel syndrome, which allowed both histopathological and microbiological examinations to be performed. A synovial tissue culture was positive for Sporothrix schenckii, and he was diagnosed with sporotrichal tenosynovitis. He received anti-fungal therapy, and the sporotrichal tenosynovitis resolved. This case suggests that MSUS is a useful modality, and sporotrichal tenosynovitis, though rare, should be considered in the differential diagnosis of RA. [Mh] Termos MeSH primário: Sistema Musculoesquelético/diagnóstico por imagem Iodeto de Potássio/uso terapêutico Sporothrix/patogenicidade Esporotricose/complicações Esporotricose/tratamento farmacológico Tenossinovite/diagnóstico Tenossinovite/etiologia [Mh] Termos MeSH secundário: Idoso Seres Humanos Masculino Sistema Musculoesquelético/microbiologia Esporotricose/microbiologia Tenossinovite/microbiologia Resultado do Tratamento Ultrassonografia [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE [Nm] Nome de substância: 1C4QK22F9J (Potassium Iodide) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171016 [Lr] Data última revisão: 171016 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170516 [St] Status: MEDLINE [do] DOI: 10.2169/internalmedicine.56.7912

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[PMID]: 28443986 [Au] Autor: Almeida-Paes R; Brito-Santos F; Figueiredo-Carvalho MHG; Machado ACS; Oliveira MME; Pereira SA; Gutierrez-Galhardo MC; Zancopé-Oliveira RM [Ad] Endereço: Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Micologia, Rio de Janeiro, RJ, Brasil. [Ti] Título: Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis. [So] Source: Mem Inst Oswaldo Cruz;112(5):376-381, 2017 May. [Is] ISSN: 1678-8060 [Cp] País de publicação: Brazil [La] Idioma: eng [Ab] Resumo: BACKGROUND: Sporothrix brasiliensis is the most virulent sporotrichosis agent. This species usually responds to antifungal drugs, but therapeutic failure can occur in some patients. Antifungal susceptibility tests have been performed on this species, but no clinical breakpoints (CBPs) are available. In this situation, minimal inhibitory concentration (MIC) distributions and epidemiological cutoff values (ECVs) support the detection of identification of resistant strains. OBJECTIVES: To study the MIC distributions of five antifungal drugs against S. brasiliensis and to propose tentative ECVs. METHODS: MICs of amphotericin B (AMB), itraconazole (ITR), ketoconazole (KET), posaconazole (POS), and terbinafine (TRB) against 335 S. brasiliensis strains were determined by the Clinical and Laboratory Standards Institute broth microdilution method. FINDINGS: The proposed ECV, in µg/mL, for AMB, ITR, KET, POS, and TRB were 4.0, 2.0, 1.0, 2.0, and 0.25, respectively. Percentages of wild-type strains in our population for the above antifungal drugs were 98.48, 95.22, 95.33, 100, and 97.67%, respectively. MAIN CONCLUSIONS: These ECVs will be useful to detect strains with resistance, to define CBPs, and to elaborate specific therapeutic guidelines for S. brasiliensis. Rational use of antifungals is strongly recommended to avoid the emergence of resistant strains and ensure the therapeutic effectiveness of sporotrichosis. [Mh] Termos MeSH primário: Antifúngicos/farmacologia Sporothrix/efeitos dos fármacos [Mh] Termos MeSH secundário: Anfotericina B/farmacologia Animais Gatos Farmacorresistência Fúngica Seres Humanos Itraconazol/farmacologia Cetoconazol/farmacologia Testes de Sensibilidade Microbiana Naftalenos/farmacologia Sporothrix/isolamento & purificação Triazóis/farmacologia [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antifungal Agents); 0 (Naphthalenes); 0 (Triazoles); 304NUG5GF4 (Itraconazole); 6TK1G07BHZ (posaconazole); 7XU7A7DROE (Amphotericin B); G7RIW8S0XP (terbinafine); R9400W927I (Ketoconazole) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170824 [Lr] Data última revisão: 170824 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170427 [St] Status: MEDLINE

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[PMID]: 28327256 [Au] Autor: Moussa TAA; Kadasa NMS; Al Zahrani HS; Ahmed SA; Feng P; Gerrits van den Ende AHG; Zhang Y; Kano R; Li F; Li S; Song Y; Dong B; Rossato L; Dolatabadi S; Hoog S [Ad] Endereço: 3​Botany and Microbiology Department, Faculty of Science, Cairo University, Giza, Egypt 2​Biological Sciences Department, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia 1​Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. [Ti] Título: Origin and distribution of Sporothrix globosa causing sapronoses in Asia. [So] Source: J Med Microbiol;66(5):560-569, 2017 May. [Is] ISSN: 1473-5644 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: PURPOSE: The aim of the study was to evaluate the main sources and epidemiological patterns and speculate on the evolutionary origin of Sporothrix globosa in Asia. METHODOLOGY: Case and case series literature on sporotrichosis in Asia from January 2007 onwards were reviewed using meta-analysis. Phylogenetic analysis of relevant S. globosa was carried out on the basis of concatenated sequences of ITS, TEF3 and CAL. A haplotype network of CAL sequences of 281 Sporothrix isolates was analysed to determine the population structure of S. globosa. RESULTS: Nearly all cases of sporotrichosis caused by S. globosa in Asia were human. In contrast to the remaining pathogenic Sporothrix species, feline transmission was exceptional; nearly all regional cat-associated cases were caused by Sporothrix schenckii. While the latter species was highly variable and showed recombination, S. globosa seemed to be a clonal offshoot, as was Sporothrix brasiliensis. The origin of the segregants was located in an area of high variability in S. schenckii with a relatively high frequency of Asian strains. CONCLUSION: In Asia, S. globosa was the prevalent species. The low diversity of S. globosa suggested a recent divergence with a founder effect of low variability from the variable ancestral species, S. schenckii. [Mh] Termos MeSH primário: Sporothrix/genética Esporotricose/epidemiologia Esporotricose/microbiologia [Mh] Termos MeSH secundário: Animais Ásia/epidemiologia Proteínas de Bactérias/genética Calmodulina/genética Doenças do Gato Gatos Evolução Molecular Variação Genética Seres Humanos Filogenia Sporothrix/isolamento & purificação Sporothrix/patogenicidade Sporothrix/ultraestrutura Esporotricose/transmissão Esporotricose/veterinária [Pt] Tipo de publicação: JOURNAL ARTICLE; META-ANALYSIS; REVIEW [Nm] Nome de substância: 0 (Bacterial Proteins); 0 (Calmodulin) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170614 [Lr] Data última revisão: 170614 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170323 [St] Status: MEDLINE [do] DOI: 10.1099/jmm.0.000451

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[PMID]: 28219829 [Au] Autor: Waller SB; Peter CM; Hoffmann JF; Picoli T; Osório LD; Chaves F; Zani JL; de Faria RO; de Mello JR; Meireles MC [Ad] Endereço: Centro de Diagnóstico e Pesquisa em Micologia Veterinária, Universidade Federal de Pelotas, Pelotas, RS, Brazil. Electronic address: waller.stefanie@yahoo.com.br. [Ti] Título: Chemical and cytotoxic analyses of brown Brazilian propolis (Apis mellifera) and its in vitro activity against itraconazole-resistant Sporothrix brasiliensis. [So] Source: Microb Pathog;105:117-121, 2017 Apr. [Is] ISSN: 1096-1208 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: This study aimed to evaluate the chemical composition and cytotoxic activity of brown Brazilian propolis and its in vitro activity against itraconazole-resistant Sporothrix brasiliensis from animal sporotrichosis. Propolis was acquired commercially and prepared as a hydroalcoholic extract. Chemical analysis was evaluated by liquid chromatography coupled to mass spectrometry of ultra-efficiency. The cell viability was evaluated by MTT test in MDBK cells of 50 to 0.09 µg/mL. For antifungal tests, twenty isolates of Sporothrix brasiliensis from dogs (n = 11) and cats (n = 9) with sporotrichosis were tested to itraconazole (16-0.0313 µg/mL) and to propolis (3.125-0.09 mg/mL) by broth microdilution technique (CLSI M38-A2), adapted to natural products. The results were expressed in minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC). Itraconazole showed activity between MIC values of 0.25 to greater than 16 µg/mL, and 88.9% (08/09) and 72.7% (08/11) of S. brasiliensis from cats and dogs, respectively, were considered itraconazole-resistant. All Sporothrix brasiliensis were sensitive to brown propolis between MIC values of 0.19-1.56 mg/mL, including the itraconazole-resistant isolates, whereas the MFC values of propolis were from 0.78 to greater than 3.125 mg/mL. Propolis maintained a medium to high cell viability between concentration of 0.78 to 0.09 µg/mL, and p-coumaric acid was the major compound. Brown Brazilian propolis is a promising antifungal candidate against sporotrichosis and more studies need to be undertaken to evaluate its safe use to understand its efficacy. [Mh] Termos MeSH primário: Antifúngicos/farmacologia Antifúngicos/toxicidade Produtos Biológicos/farmacologia Produtos Biológicos/toxicidade Própole/farmacologia Própole/toxicidade Sporothrix/efeitos dos fármacos [Mh] Termos MeSH secundário: Animais Antifúngicos/química Antifúngicos/isolamento & purificação Produtos Biológicos/química Produtos Biológicos/isolamento & purificação Brasil Doenças do Gato/microbiologia Gatos Linhagem Celular Sobrevivência Celular/efeitos dos fármacos Cromatografia Líquida Doenças do Cão/microbiologia Cães Farmacorresistência Fúngica Itraconazol/farmacologia Espectrometria de Massas Testes de Sensibilidade Microbiana Viabilidade Microbiana/efeitos dos fármacos Sporothrix/isolamento & purificação Esporotricose/veterinária [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antifungal Agents); 0 (Biological Products); 304NUG5GF4 (Itraconazole); 9009-62-5 (Propolis) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170417 [Lr] Data última revisão: 170417 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170222 [St] Status: MEDLINE

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[PMID]: 28140444 [Au] Autor: Gonçalves AC; Ferreira LS; Manente FA; de Faria CMQG; Polesi MC; de Andrade CR; Zamboni DS; Carlos IZ [Ad] Endereço: Department of Clinical Analysis, Faculty of Pharmaceutical Sciences of Araraquara, São Paulo State University (FCF/UNESP), Araraquara, Brazil. [Ti] Título: The NLRP3 inflammasome contributes to host protection during Sporothrix schenckii infection. [So] Source: Immunology;151(2):154-166, 2017 Jun. [Is] ISSN: 1365-2567 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Sporotrichosis is a mycosis caused by fungi from the Sporothrix schenckii species complex, whose prototypical member is Sporothrix schenckii sensu stricto. Pattern recognition receptors (PRRs) recognize and respond to pathogen-associated molecular patterns (PAMPs) and shape the following adaptive immune response. A family of PRRs most frequently associated with fungal recognition is the nucleotide-binding oligomerization domain-like receptor (NLR). After PAMP recognition, NLR family pyrin domain-containing 3 (NLRP3) binds to apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 to form the NLRP3 inflammasome. When activated, this complex promotes the maturation of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 and cell death through pyroptosis. In this study, we aimed to evaluate the importance of the NLRP3 inflammasome in the outcome of S. schenckii infection using the following three different knockout (KO) mice: NLRP3 , ASC and caspase-1 . All KO mice were more susceptible to infection than the wild-type, suggesting that NLRP3-triggered responses contribute to host protection during S. schenckii infection. Furthermore, the NLRP3 inflammasome appeared to be critical for the ex vivo release of IL-1ß, IL-18 and IL-17 but not interferon-γ. Additionally, a role for the inflammasome in shaping the adaptive immune response was suggested by the lower frequencies of type 17 helper T (Th17) cells and Th1/Th17 but not Th1 cells in S. schenckii-infected KO mice. Overall, our results indicate that the NLRP3 inflammasome links the innate recognition of S. schenckii to the adaptive immune response, so contributing to protection against this infection. [Mh] Termos MeSH primário: Inflamassomos/imunologia Inflamassomos/metabolismo Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo Sporothrix/imunologia Esporotricose/imunologia [Mh] Termos MeSH secundário: Animais Masculino Camundongos Camundongos Endogâmicos C57BL Camundongos Knockout Proteína 3 que Contém Domínio de Pirina da Família NLR/deficiência Sporothrix/citologia Esporotricose/microbiologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Inflammasomes); 0 (NLR Family, Pyrin Domain-Containing 3 Protein); 0 (Nlrp3 protein, mouse) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171002 [Lr] Data última revisão: 171002 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170201 [St] Status: MEDLINE [do] DOI: 10.1111/imm.12719

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MEDLINE

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[PMID]: 28133872 [Au] Autor: Han HS; Kano R; Chen C; Noli C [Ad] Endereço: Han Veterinary Surgery, 50 JLN Molek 2/2, TMN Molek, 81100, Johor Bahru, Johor, Malaysia. [Ti] Título: Comparison of two in vitro antifungal sensitivity tests and monitoring during therapy of Sporothrix schenckii sensu stricto in Malaysian cats. [So] Source: Vet Dermatol;28(1):156-e32, 2017 Feb. [Is] ISSN: 1365-3164 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: Feline sporotrichosis is common in Malaysia. Thermosensitivity and effects of azole treatment on fungal susceptibility are unknown. OBJECTIVES: To evaluate thermotolerance and antifungal susceptibility of feline Malaysian Sporothrix isolates, compare microdilution (MD) and E-test results, and investigate changes in susceptibility during azole therapy. METHODS: Sporothrix schenckii sensu stricto was isolated from 44 cats. Thermotolerance was determined via culture at 37°C for 7 days. Susceptibility to itraconazole (ITZ), ketoconazole (KTZ) and terbinafine (TRB) was assessed in 40 isolates by MD; to amphotericin B (AMB), KTZ, ITZ, fluconazole (FLC) and posaconazole (POS) by E-test. Results were statistically compared by Pearson's Product Moment. In eight ketoconazole treated cats, susceptibility testing to itraconazole and ketoconazole was repeated every two months for six months. RESULTS: Thermotolerance was observed in 36 of 44 (82%) isolates. Assuming that isolates growing at antifungal concentrations ≥4 mg/mL were resistant, all were resistant on E-test to FLC and AMB, 11 (28%) to POS, 6 (15%) to ITZ and 1 (3%) to KTZ. On MD, 27 of 40 (68%) were resistant to TRB, 2 (5%) to ITZ and 3 (8%) to KTZ. There was no correlation between E-test and MD results (KTZ r = 0.10, P = 0.54, and ITZ r = 0.11, P = 0.48). MD values for ITZ and KTZ did not exceed 4 mg/L during KTZ therapy. CONCLUSION: The majority of feline isolates in Malaysia are thermosensitive. Lack of correlation between E-test and MD suggests that the E-test is unreliable to test antifungal susceptibility for Sporothrix spp. compared to MD. KTZ was the antifungal drug with the lowest MIC. Prolonged KTZ administration may not induce changes in antifungal susceptibility. [Mh] Termos MeSH primário: Antifúngicos/uso terapêutico Doenças do Gato/tratamento farmacológico Testes de Sensibilidade Microbiana/veterinária Sporothrix/efeitos dos fármacos Esporotricose/veterinária [Mh] Termos MeSH secundário: Anfotericina B/uso terapêutico Animais Gatos/microbiologia Técnicas In Vitro Itraconazol/uso terapêutico Cetoconazol/uso terapêutico Malásia Testes de Sensibilidade Microbiana/métodos Naftalenos/uso terapêutico Esporotricose/tratamento farmacológico Esporotricose/microbiologia Triazóis/uso terapêutico [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antifungal Agents); 0 (Naphthalenes); 0 (Triazoles); 304NUG5GF4 (Itraconazole); 6TK1G07BHZ (posaconazole); 7XU7A7DROE (Amphotericin B); G7RIW8S0XP (terbinafine); R9400W927I (Ketoconazole) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170627 [Lr] Data última revisão: 170627 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170131 [St] Status: MEDLINE [do] DOI: 10.1111/vde.12417

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