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BioMAP screening procedure could streamline search for new antibiotics
Date:11/26/2012

The researchers started with a training set of 72 commercially available antibiotics and tested them all against a panel of 15 bacterial strains, including a broad range of clinically important pathogens. The commercial antibiotics were chosen to include multiple members of all of the main classes of antibiotics. Parallel screening of the antibiotics against all 15 strains was performed using robotic equipment at the UCSC Chemical Screening Center.

The tests yielded a characteristic pattern of activity, or BioMAP profile, for each antibiotic, and antibiotics within the same class had similar profiles. Analysis using hierarchical clustering methods showed that the BioMAP profiles are highly diagnostic for the known structural classes of antibiotics. The researchers then showed that the procedure could be used to classify compounds present in natural product extracts and identify novel antibiotics.

"The first step was to profile a lot of known drugs and see if BioMAP profiles were diagnostic for specific structural classes. The second step was to profile a library of unknowns from our natural product collection, eliminate all extracts with profiles that matched known classes of antibiotics, and focus on those that look unique," Linington said.

One extract from the lab's natural product library looked particularly interesting and led to the isolation of a novel antibiotic compound. Named arromycin, the compound is a napthoquinone antibiotic with a number of unusual structural features.

"Arromycin probably won't lead to a new antibiotic drug--there are a number of structural liabilities from a drug development standpoint--but its discovery is a proof of principal that the BioMAP platform works for finding novel compounds," Linington said. "Our library has tens of thousands of chemicals. If we want to find new antibiotics, this is an excellent way to do that without wasting time rediscovering known structures."


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Contact: Tim Stephens
stephens@ucsc.edu
831-459-2495
University of California - Santa Cruz
Source:Eurekalert

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