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

Author(s)

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

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 25, n. 23, p. 27-pg., 2024-12-01.

Abstract

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)

• FAPESP's process: 22/16198-3 - Prospection of secondary metabolites of Actinomycetes with inhibitory activity against clinical and environmental pathogenic fungi
• Grantee: Angelica Zaninelli Schreiber
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/12553-3 - Organization, diversification and expansion of records of Unicamp culture collections: proposal of a pilot structure for the constitution of an integrated network
• Grantee: Derlene Attili de Angelis
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants