Enhancement of antibiotic and secondary metabolite detection from filamentous fungi by growth on nutritional arrays

• Published in: Journal of applied microbiology Vol. 104; no. 6; pp. 1644 - 1658
• Main Authors: Bills, G.F, Platas, G, Fillola, A, Jiménez, M.R, Collado, J, Vicente, F, Martín, J, González, A, Bur-Zimmermann, J, Tormo, J.R, Peláez, F
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.06.2008; Blackwell Publishing Ltd; Blackwell Science
• Subjects: Antifungal Agents - analysis; Antifungal Agents - chemistry; antifungals; Biological and medical sciences; Bioreactors - microbiology; Candida albicans - drug effects; Candida albicans - growth & development; Culture Media; Fermentation; Fundamental and applied biological sciences. Psychology; Fungi - metabolism; high throughput screening; Microbial Sensitivity Tests; Microbiology; microfermentation; Mycology - instrumentation; Mycology - methods; OSMAC; secondary metabolite induction; High throughput screening; secondary metabolite induction; Growth; Induction; Applied microbiology; Metabolite; OSMAC; antifungals; Fungi; Antibiotic; Antifungal agent; Analysis method; microfermentation; Detection
• ISSN: 1364-5072; 1365-2672
• DOI: 10.1111/j.1365-2672.2008.03735.x

We asked to what extent does the application of the OSMAC (one strain, many compounds) approach lead to enhanced detection of antibiotics and secondary metabolites in fungi? Protocols for bacterial microfermentations were adapted to grow fungi in nutritional arrays. Protocols for microfermentations of non-sporulating fungi were validated using known antifungal-producing fungi. Detection of antifungal activity was often medium dependent. The effects of medium arrays and numbers of strains on detection of antifungal signals were modelled by interpolation of rarefaction curves derived from matrices of positive and negative extracts. Increasing the number of fermentation media for any given strain increased the probability of detection of growth inhibition of Candida albicans. Increasing biodiversity increased detection of antifungal phenotypes, however, nutritional arrays could partly compensate for lost antibiotic phenotypes when biodiversity was limiting. Growth and extraction in microtiter plates can enable a discovery strategy emphasizing low-cost medium arrays that can better exploit the metabolic potential of strains. Increasing fermentation parameters raise the probability of detecting bioactive metabolites from strains. The protocols can be used to pre-select strains and their growth conditions for scale up that will most likely yield antibiotics and secondary metabolites.