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
Centro de Investigación Básica, Merck Sharp & Dohme de España, S.A., Madrid, Spain.
J Appl Microbiol. 2008 Jun;104(6):1644-58. doi: 10.1111/j.1365-2672.2008.03735.x. Epub 2008 Feb 19.
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.
我们探究了采用OSMAC（一株多化合物）方法在多大程度上能提高真菌中抗生素和次级代谢产物的检测水平。对细菌微发酵方案进行了调整，以在营养阵列中培养真菌。
使用已知产抗真菌物质的真菌对非产孢真菌的微发酵方案进行了验证。抗真菌活性的检测通常依赖于培养基。通过对正负提取物矩阵得出的稀疏曲线进行插值，模拟了培养基阵列和菌株数量对抗真菌信号检测的影响。对于任何给定菌株，增加发酵培养基的数量会增加检测到白色念珠菌生长抑制的概率。生物多样性的增加提高了抗真菌表型的检测率，然而，当生物多样性有限时，营养阵列可以部分弥补抗生素表型的损失。
在微量滴定板中进行生长和提取能够实现一种发现策略，该策略强调低成本的培养基阵列，从而能更好地挖掘菌株的代谢潜力。
增加发酵参数会提高从菌株中检测到生物活性代谢产物的概率。这些方案可用于预先选择菌株及其扩大规模的生长条件，最有可能产生抗生素和次级代谢产物。
