Enhancing Antifungal Drug Discovery Through Co-Culture with Antarctic Streptomyces albidoflavus Strain CBMAI 1855

Autor(es)

Giordano, Ana Luisa Perini Leme ; Rodrigues, Marili Villa Nova ; dos Santos, Karen Gabriela Araujo ; Legabao, Barbara Cipulo ; Pontes, Lais ; de Angelis, Derlene Attili ; Garboggini, Fabiana Fantinatti ; Schreiber, Angelica Zaninelli

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 25, n. 23, p. 27-pg., 2024-12-01.

Resumo

Fungal infections pose a growing public health threat, creating an urgent clinical need for new antifungals. Natural products (NPs) from organisms in extreme environments are a promising source for novel drugs. Streptomyces albidoflavus CBMAI 1855 exhibited significant potential in this regard. This study aimed to (1) assess the antifungal spectrum of the CBMAI 1855 extract against key human pathogens, (2) elicit NP production through co-cultivation with fungi, correlating the metabolites with the biosynthetic gene clusters (BGCs), and (3) perform in silico toxicity predictions of the identified compounds to analyze their suitability for drug development. The crude extract of CBMAI 1855 exhibited broad-spectrum antifungal activity. The metabolomic analysis identified antifungal NPs such as antimycin A, fungimycin, surugamides, 9-(4-aminophenyl)-3,7-dihydroxy-2,4,6-trimethyl-9-oxo-nonoic acid, and ikarugamycin, with the latter two predicted to be the most suitable for drug development. Genome mining revealed three cryptic BGCs potentially encoding novel antifungals. These BGCs warrant a detailed investigation to elucidate their metabolic products and harness their potential. CBMAI 1855 is a prolific producer of multiple antifungal agents, offering a valuable source for drug discovery. This study highlights the importance of exploring microbial interactions to uncover therapeutics against fungal infections, with a detailed exploration of cryptic BGCs offering a pathway to novel antifungal compounds. (AU)

• Processo FAPESP: 22/16198-3 - Prospecção de metabólitos secundários de Actinobactérias com atividade inibitória frente a fungos patogênicos clínicos e ambientais
• Beneficiário: Angelica Zaninelli Schreiber
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/12553-3 - Organização, diversificação e ampliação de registros de coleções microbiológicas da Unicamp: proposta de uma estrutura piloto para constituição de uma rede integrada
• Beneficiário: Derlene Attili de Angelis
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular