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Advisor(s)
Abstract(s)
Vários fungos resistentes aos triazóis, incluindo Aspergillus fumigatus são uma causa emergente de infeções sistémicas oportunistas, já que os Aspergillus spp. são dos fungos mais prevalentes em ambientes ocupacionais. O aumento da resistência aos antifúngicos torna imprescindível a avaliação de novos compostos com propriedades antifúngicas e/ou sinérgicas, para serem utilizados como adjuvantes na terapia fúngica combinada. A epigalocatequina-3-galato (EGCG), o principal constituinte do chá verde, demonstrou propriedades anti-infeciosas em vários estudos. Objetivou-se avaliar o potencial antifúngico da EGCG contra isolados de Aspergillus fumigatus resistentes a triazóis, colhidos em diferentes ambientes ocupacionais, e os potenciais efeitos sinérgicos entre a EGCG e os antifúngicos comumente usados – itraconazole (ITR), voriconazole (VOR) e posaconazole (POS). Os isolados de Aspergillus fumigatus resistentes a triazóis (N=3) foram cultivados em Sabouraud e preparadas suspensões fúngicas (OD=0.060) com EGCG em concentrações
finais de 250µg/mL, 100µg/mL, 50µg/mL, 25µg/mL e sem EGCG. Cada suspensão foi inoculada em RPMI-1640 e Sabouraud suplementados com 4μg/mL ITR, 2μg/mL VOR, 0.5μg/mL POS ou sem antifúngico e incubada a 34-37ºC durante 7 dias (adaptado do método EUCAST E.Def 10.1). Um isolado cresceu em RPMI-1640 suplementado apenas com 2μg/mL VOR e na presença de 25 e 50 μg/mL de EGCG, mas não apresentou crescimento em concentrações de EGCG superiores a 100μg/mL, indicando sensibilização do isolado. Estes resultados sugerem que a EGCG poderá ser usada como potencial adjuvante na terapia antifúngica combinada contra Aspergillus fumigatus resistentes a triazóis. Não obstante, mais estudos com amostras maiores devem ser realizados antes da translação destes resultados para abordagens terapêuticas.
ABSTRACT - Systemic-opportunistic fungal infections caused by triazole-resistant fungi, including Aspergillus fumigatus, are an emergent cause of human disease worldwide, as Aspergillus spp. is one of the most prevalent fungi in occupational environments. The antifungal drugs resistance makes it imperative to assess new compounds with antimicrobial and/or synergistic properties, to be utilized as adjuvants in combination antifungal therapy. Epigallocatechin-3-gallate (EGCG), the main green tea constituent, has demonstrated anti-infective properties in several studies. The aim was to assess the antifungal potential of EGCG against triazole resistant Aspergillus fumigatus isolates collected in different occupational settings, and the potential synergistic effects between ECGC and commonly used antifungal drugs – itraconazole (ITR), voriconazole (VOR), and posaconazole (POS). Triazole-resistant Aspergillus fumigatus isolates (N=3) were grown in Sabouraud dextrose 4% agar. Inoculum suspensions (OD=0.060) were prepared with EGCG at final concentrations of 250µg/mL, 100µg/mL, 50µg/mL, 25µg/mL and with no EGCG. Each suspension was spread onto RPMI1640 medium and Sabouraud dextrose 4% agar supplemented with 4μg/mL ITR, 2μg/mL VOR, 0.5μg/mL POS, or with no supplementation, and incubated at 34-37ºC for 7 days (adapted from the EUCAST E.Def 10.1 method). One isolate grew on RPMI-1640 supplemented with 2μg/mL VOR alone and with 25 and 50 μg/mL of EGCG, with no visible growth with EGCG concentrations above 100μg/mL, implying chemosensitization of the isolate. These results suggest that EGCG may be used as a possible adjuvant for combination antifungal therapy against triazole-resistant Aspergillus fumigatus. However further studies with greater sample sizes should take place before the translation of these results into clinically relevant strategies.
ABSTRACT - Systemic-opportunistic fungal infections caused by triazole-resistant fungi, including Aspergillus fumigatus, are an emergent cause of human disease worldwide, as Aspergillus spp. is one of the most prevalent fungi in occupational environments. The antifungal drugs resistance makes it imperative to assess new compounds with antimicrobial and/or synergistic properties, to be utilized as adjuvants in combination antifungal therapy. Epigallocatechin-3-gallate (EGCG), the main green tea constituent, has demonstrated anti-infective properties in several studies. The aim was to assess the antifungal potential of EGCG against triazole resistant Aspergillus fumigatus isolates collected in different occupational settings, and the potential synergistic effects between ECGC and commonly used antifungal drugs – itraconazole (ITR), voriconazole (VOR), and posaconazole (POS). Triazole-resistant Aspergillus fumigatus isolates (N=3) were grown in Sabouraud dextrose 4% agar. Inoculum suspensions (OD=0.060) were prepared with EGCG at final concentrations of 250µg/mL, 100µg/mL, 50µg/mL, 25µg/mL and with no EGCG. Each suspension was spread onto RPMI1640 medium and Sabouraud dextrose 4% agar supplemented with 4μg/mL ITR, 2μg/mL VOR, 0.5μg/mL POS, or with no supplementation, and incubated at 34-37ºC for 7 days (adapted from the EUCAST E.Def 10.1 method). One isolate grew on RPMI-1640 supplemented with 2μg/mL VOR alone and with 25 and 50 μg/mL of EGCG, with no visible growth with EGCG concentrations above 100μg/mL, implying chemosensitization of the isolate. These results suggest that EGCG may be used as a possible adjuvant for combination antifungal therapy against triazole-resistant Aspergillus fumigatus. However further studies with greater sample sizes should take place before the translation of these results into clinically relevant strategies.
Description
Project "Resistant mycobiota and mycotoxigenic profile of tea and medicinal plants” (IPL/2020/TEAResMyc_ESTeSL).
Project "Resistance modulation and epigenetic divergence in resistant phenotypic profiles of Staphylococcus Aureus” (IPL/2020/EpiResistanceSA_ESTeSL).
Mestrado em Tecnologias Clínico-Laboratoriais
Project "Resistance modulation and epigenetic divergence in resistant phenotypic profiles of Staphylococcus Aureus” (IPL/2020/EpiResistanceSA_ESTeSL).
Mestrado em Tecnologias Clínico-Laboratoriais
Keywords
Epigallocatechin-3-gallate Aspergillus fumigatus Antifungal resistance Synergism Epigalocatequina-3-galato Resistência antifúngica Sinergismo Projeto IPL/2020/TEAResMyc_ESTeSL Projeto IPL/2020/EpiResistanceSA_ESTeSL
Citation
Ponte TS. Epigallocatechin-3-gallate antimycotic and azole resistant modulator potential against resistant fungi [dissertation]. Lisboa: Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa; 2021.
Publisher
Instituto Politécnico de Lisboa, Escola Superior de Tecnologia da Saúde de Lisboa