Bacterial co-culture leads to novel antibiotics
Historically, most antibacterial compounds have been isolated from natural bacterial products. This approach was largely abandoned by pharmaceutical companies under the belief that the discovery of new anti-bacterial compounds is unlikely. However, the recent sequencing of bacterial genomes has demonstrated the presence of many more gene clusters for the biosynthesis of antibiotic-like metabolites than previously envisioned. Under standard laboratory conditions, cryptic gene clusters with antibiotic effects are often silent and require new strategies to induce their expression. Towards this goal, the EU-funded COCULMICRO (Cocultivation of microorganisms as a strategy for discovery of new natural products with antimicrobial properties) project proposed to co-culture microorganisms and identify novel microbial natural products. To begin with, researchers isolated over 300 isolates of actinomycetes from different spots in southern Spain and carried out pairwise fermentations. The rationale behind this study was to identify some kind of cross-stimulation phenomena that is shared by pairs of microorganisms for the production of secondary metabolites. To identify these pairs, scientists performed high-throughput antibiosis assays against a panel of human pathogenic bacteria (methicillin-resistant Staphylococcus aureus, Acinetobacter baumanii and Candida albicans). In addition, to identify non-active metabolites released during the co-culture they performed UHPLC-comparative metabolite profiling. A total of 14 co-cultures were identified for the presence of compounds that were not produced during axenic fermentation. Structural analysis of these compounds could lead to novel molecules with anti-bacterial activity. Overall, the COCULMICRO activities underscored the validity of exploiting bacterial biosynthetic pathways towards the identification of novel antibiotics. Despite limitations in upscaling the proposed co-culture method, the inherent mechanisms responsible for bacterial interactions open new avenues for their implementation in the pharmaceutical industry.
Keywords
Bacteria, co-culture, antibiotics, metabolite, actinomycetes, axenic fermentation