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Under the Sea: Taking the Search for Novel Antibiotics to New Depths

By Prof. Marcel Jaspars, head of the Marine Biodiscovery Centre at the University of Aberdeen, and project leader of PharmaSea

We’ve all taken antibiotics for one reason or another in our lives. They have revolutionized the medical field in the 20th century, and together with vaccinations have led to the eradication of many once life-threatening diseases. However, history has taught us that too much of a good thing can have dire consequences. The effectiveness and availability of antibiotics eventually led to overuse, causing the very bacteria these drugs were designed for to evolve and develop resistance. Our society has become dependent on this form of treatment to remain healthy so bacterial pathogens that are unaffected by antibiotics are a horror of modern medicine.

In fact, the World Health Organization (WHO) has recognized the increasing number of drug-resistant microbes as a growing health crisis. A 2014 WHO report referred to the epidemic as, "an increasingly serious threat to global public health that requires action across all government sectors and society.” Like any other pharmaceutical, antibiotics are derived from natural products that have already been used and studied for centuries, which is the root of the problem. Without novel, advanced methods of drug discovery, antibiotic resistance will continue to compromise our health and well-being.

Enter the PharmaSea project—a consortium of 24 partners from 13 countries. My team from the Marine Biodiscovery Centre at the University of Aberdeen is joined by world-leading experts from Belgium, UK, Norway, Spain, Ireland, Germany, Italy, Austria, and Denmark. Our primary goal is to collect and screen samples from some of the hottest, deepest, and coldest places on the planet.

Why go through all this trouble? Simple. Well…not that simple, but by choosing deep and cold marine environments, we hope to uncover marine microbes—a little-investigated source in drug discovery—and new bioactive compounds for use in the development of antibiotics. The organisms that live in these environments are considered to be a valuable source of non-traditional bioactive compounds because of their ability to survive in extreme conditions. As you can probably guess, getting to these remote locations is not easy, which is why—up until now—only a handful of samples from deep-sea trenches had ever been collected and studied. Given the time and resources required to obtain a limited amount of samples, each research group uses advanced selective isolation techniques, utilizes polyphasic taxonomy, and assesses biosynthetic potential using genome scanning. Also, to speed up the discovery of chemical novelty chemometrics, our team relies on datamining and computer aided structure elucidation.

ACD/Labs and the capabilities of its products are essential to this process. With the help of ACD/Labs’ software, PharmaSea researchers have dereplicated more than 300 extracts, and, as a result, have identified 10 novel compounds that merit further research. The automation capabilities offered by ACD/MS Workbook Suite cuts the amount of time required for dereplication of LC/MS peaks from days to minutes. Also, ACD/Structure Elucidator Suite is extremely helpful for the next stage of the method—structure characterization. By removing bias from the data interpretation process, our team is able to identify structures that they would have otherwise overlooked, and filtering against the products’ built in a database significantly reduces the amount of time needed to carry out these tasks. 

Before enlisting the services of ACD/Labs, my team relied on various techniques and several different instrument vendors. Now it doesn’t matter what instrument the raw data comes from—the ACD/Spectrus Platform can handle all of it. As an added bonus, we hope to make a lasting contribution from the insights learned through the PharmaSea project. Right now, we are working on an extensive natural products database that includes interpreted MS, MS/MS, NMR, and UV spectra with assigned structures for chemical context. Eventually, this will speed up the identification process of unknown components from marine sample extracts. The time saved and intelligence gained as a direct result of ACD/Labs’ suite of offerings is invaluable for our team, the advancement of natural products research and our ultimate goal of improving drug discovery.

If you’d like to learn more about the PharmaSea project visit our website here.

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