BioMAP screening procedure could streamline search for new antibiotics

November 26, 2012

Researchers at the University of California, Santa Cruz, have developed a new strategy for finding novel antibiotic compounds, using a diagnostic panel of bacterial strains for screening chemical extracts from natural sources.

warn of a looming antibiotic crisis due to the steady increase in antibiotic resistance and a dramatic decline in the development of . Most currently available are derived from produced by microorganisms such as bacteria and fungi. New antibiotics developed by drug companies are often synthetically tailored variations of existing classes of antibiotics. To combat the problem of , however, researchers desperately want to find antibiotics with completely novel structures and modes of action.

The new , called BioMAP (antibiotic mode of action profile), promises to streamline the discovery of new antibiotics from natural sources by providing a low-cost, high-throughput platform for identifying compounds with novel antibiotic properties.

"If you take a library of natural product extracts and screen them against a bacterial target, you will find a lot of antibacterial compounds, but almost all of them will be known structures," said Roger Linington, assistant professor of chemistry and biochemistry at UC Santa Cruz. "BioMAP is a new way to look at so that you're not wasting time and energy chasing things that turn out to be well-studied compounds of little therapeutic value."

Linington's lab focuses on marine natural products—mostly microorganisms isolated from —as a source of lead compounds for drug discovery. The BioMAP project was led by Weng Ruh Wong, who joined the lab as a postdoctoral fellow in the -Malaysia Program. Wong is first author of a paper presenting the BioMAP screening procedure published in the November 21 issue of Chemistry & Biology.

The researchers started with a training set of 72 commercially available antibiotics and tested them all against a panel of 15 , 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."

It makes sense to look for antibiotics in environments where bacteria compete with one another, he said. About 80 percent of currently available antibiotics are derived from natural products, mostly from soil microorganisms. But because natural products have been studied so extensively, the rate of return in terms of novel chemistry has decreased precipitously.

"Almost all of the new antibiotics are 'me too' drugs that work in the same way as an existing drug," Linington said. "The paucity of new therapeutic options for bacterial infections is a well-recognized and ongoing issue, and it is a major emerging threat to public health, both nationally and on a global scale."

Explore further: 'Resuscitating' antibiotics to overcome drug resistance

Related Stories

'Resuscitating' antibiotics to overcome drug resistance

March 28, 2012
Combining common antibiotics with additional compounds could make previously resistant bacteria more susceptible to the same antibiotics. 'Resuscitation' of existing antibiotics has the potential to make infections caused ...

Canada should ban off-label antibiotic use in agriculture: CMAJ

June 4, 2012
Canada should ban off-label use of antibiotics in farm animals because it contributes significantly to antibiotic resistance in humans, states an editorial in CMAJ (Canadian Medical Association Journal).

Recommended for you

Study suggests ending opioid epidemic will take years

July 20, 2017
The question of how to stem the nation's opioid epidemic now has a major detailed response. A new study chaired by University of Virginia School of Law Professor Richard Bonnie provides extensive recommendations for curbing ...

Team-based model reduces prescription opioid use among patients with chronic pain by 40 percent

July 17, 2017
A new, team-based, primary care model is decreasing prescription opioid use among patients with chronic pain by 40 percent, according to a new study out of Boston Medical Center's Grayken Center for Addiction Medicine, which ...

Private clinics' peddling of unproven stem cell treatments is unsafe and unethical

July 7, 2017
Stem cell science is an area of medical research that continues to offer great promise. But as this week's paper in Science Translational Medicine highlights, a growing number of clinics around the globe, including in Australia, ...

Popular heartburn drugs linked to higher death risk

July 4, 2017
Popular heartburn drugs called proton pump inhibitors (PPIs) have been linked to a variety of health problems, including serious kidney damage, bone fractures and dementia. Now, a new study from Washington University School ...

Most reproductive-age women using opioids also use another substance

June 30, 2017
The majority of reproductive-age and pregnant women who use opioids for non-medical purposes also use at least one other substance, ranging from nicotine or alcohol to cocaine, according to a University of Pittsburgh Graduate ...

At-risk chronic pain patients taper opioids successfully with psychological tools

June 28, 2017
Psychological support and new coping skills are helping patients at high risk of developing chronic pain and long-term, high-dose opioid use taper their opioids and rebuild their lives with activities that are meaningful ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.