Metabolites from endophytic Aspergillus fumigatus and their in vitro effect against the causal agent of tuberculosis

Abstract

Tuberculosis (TB) remains one of the most deadly communicable infectious diseases, causing 1.4 million deaths in 2015 worldwide due to many conditions, including the inadequate treatment and the emergence of multidrug-resistant strains of the causal agent, Mycobacterium tuberculosis. Therefore, drugs developed from natural sources, as microorganisms and plant extracts, are a frequent target for the research and discovery of antimicrobial compounds. The current study started the characterization of compounds produced by an Aspergillus fumigatus isolated from copaíba (Copaifera multijuga) that efficiently inhibits M. tuberculosis by releasing the compounds into the fermentation broth under specific culture conditions. A preliminary assay was carried out with a correlate species, M. smegmatis, aiming to detect an antimicrobial effect related to A. fumigatus fermentation broth. The direct use of this substrate in antibiosis assays againstM. tuberculosis H 37 Rv strain (ATCC 27294) allowed the detection of antimicrobial activity with a minimal inhibitory concentration of 256 μg mL -1 , demonstrating that purification processes developed by the Biotage Flash Chromatography System are robust and reliable techniques for purification of compounds from natural sources. Also, this chromatographic system can be used in combination with specific biochemical tests, improving the search for reliable results. We conclude that this fraction can express a broad action range, inhibiting both Mycobacterium species used as target organisms.KEYWORDS: Mycobacterium spp., antimicrobial activity, copaíba, chromatography Metabolitos de Aspergillus fumigatus endofítico e seu efeito in vitro contra o agente causal da tuberculose RESUMO A tuberculose continua a ser uma das doenças infecciosas transmissíveis mais mortais, causando 1,4 milhão de mortes em 2015 em todo o mundo devido a vários fatores, incluindo o tratamento inadequado e o surgimento de cepas multirresistentes do agente causal, Mycobacterium tuberculosis. Portanto, as drogas desenvolvidas a partir de fontes naturais, como micro-organismos e extratos de plantas, são um alvo freqüente para a pesquisa e descoberta de compostos antimicrobianos. O presente estudo foi um ponto de partida para caracterizar compostos produzidos por um Aspergillus fumigatus isolado de copaíba (Copaifera multijuga) que inibe eficientemente M. tuberculosis, liberando os compostos no caldo de fermentação em condições de cultura específicas. Realizou-se um ensaio preliminar com uma espécie correlata, M. smegmatis, com o objetivo de detectar um efeito antimicrobiano relacionado ao caldo de fermentação de A. fumigatus. O uso direto deste substrato em ensaios de antibiose contra a estirpe H37Rv de M. tuberculosis (ATCC 27294) permitiu a detecção de atividade antimicrobiana com uma concentração inibitória mínima de 256 μg mL -1 , demonstrando que os processos de purificação desenvolvidos pelo Biotage Flash Chromatography System são técnicas robustas e confiáveis para purificar compostos de fontes nat...

Overview on antibacterial metabolites from terrestrialAspergillusspp

“…The fractions of the fermentation broth were obtained by different chromatographic techniques and tested against Mycobacterium smegmatis and M. tuberculosis. The results showed that F4 fraction had positive antimycobacterial activity, with MIC value of 256 μg ml −1 (Silva et al 2018).…”

Pharmacological Potential of Fungal Endophytes Associated with Medicinal Plants: A Review

“…associated with the leaves of Pandanus amaryllifolius . Furthermore, in vitro studies of the effects of various metabolites secreted from fungal endophytes against the etiological agents of tuberculosis have been reported [ 72 ].…”

Bioprospecting and biodiversity investigations of endophytic fungi isolated from medicinal plants and mosses

“…fumigatus isolated from different plants proved to be synthesising a wide variety of bioactive compounds (Silva et al 2018;Liu et al 2004;Ding et al 2013). Indeed, extensive research in hostendophyte interaction should be conducted for targeting endophytes in bioprospecting (e) The medicinal plants are an excellent source for bioprospecting endophytes.…”