Use of MALDI-TOF mass spectrometry and IDBac to mine for understudied bacterial genera from the environment

Bacterial natural products have greatly contributed to the global drug discovery effort. Further, the incorporation of understudied bacterial taxa into discovery pipelines remains a promising approach to supply much needed chemical diversity to this effort. Unfortunately, researchers lack rapid and efficient techniques to accomplish this. Here we present an approach that employs matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) and the bioinformatics platform IDBac to perform targeted isolation of understudied bacteria from environmental samples. A dendrogram of MS protein spectra from 479 unknown bacterial isolates was seeded with spectra from 50 characterized strains that represented target understudied genera. This method was highly effective at identifying representatives from target taxa, demonstrating an 86.3% success rate when an estimated genus level cutoff was implemented in the dendrogram. Overall, this study shows the potential of MALDI-MS/IDBac to mine environmental bacterial isolate collections for target taxa in high-throughput, particularly in the absence of proprietary software. It also provides a cost-effective alternative to morphology and gene-sequencing analyses that are typically used to guide identification and prioritization strategies from large bacterial isolate collections.