Researcher helps develop new technique to explore ocean microbes

When Southern Methodist University (SMU) researcher Alexander Chase was a young boy, he was fascinated by the diversity of plants in Earth’s tropical rainforests. He wondered what new species might be out there, waiting to be discovered. That’s why he’s now collecting samples from Earth’s oceans using a new technique called small molecule in situ capture (SMIRC), which could be the first step in discovering compounds that will lead to next-generation antibiotics.

Microbial natural products originate from microorganisms (microbes) and are the source of many of today’s essential medicines, including most antibiotics. Microbes are too small to be seen without a microscope and produce a wide variety of chemical compounds over the course of their lives, some of which are useful for pharmaceutical applications. Traditionally, these compounds are discovered using a “microbe-first” approach, where individual strains are grown in the laboratory from a sample collected in nature.

While this method is effective, it has become increasingly difficult for researchers to use it to discover new chemical “scaffolds,” which serve as the basis for building chemical compounds. Chemical scaffolds are a critical resource for drug discovery.

“Right now, when we collect new samples and grow the microbes, we’re finding structures that are essentially very similar to the ones we already know,” says Chase, an assistant professor in the Roy M. Huffington Department of Earth Sciences.

“Over the past few decades, it has been very difficult to find anything new with the ‘microbe first’ approach, which essentially limits us to the same or similar bacterial strains and their chemical compounds that represent only a fraction of the natural diversity in the ocean. That’s where SMIRC comes in, allowing us to explore the unknown.”

A recent study published in the journal Nature Communications A study by Chase and researchers at the University of California, San Diego and the University of California, San Francisco explains how SMIRC made it possible to collect microbial natural products where they are produced in nature, without having to grow them in a lab. It used an absorbent resin called HP-20, which acts like a sponge to capture chemicals released by the microbes.

The researchers used SMIRC in areas covered in seagrass near San Diego. Among the chemicals collected, they found an antibiotic compound and a chemical called chrysoeriol, which is plant-based and has antibacterial properties. A modified version of SMIRC was then used by mixing HP-20 with agar, a substance that promotes the growth of microbes. This second experiment yielded Aplysiopsene A, which demonstrated the continued success of SMIRC in recovering compounds.

A third test was conducted with SMIRC in a protected marine reserve in Cabrillo National Monument. The technique allowed for larger samples containing more complex chemical mixtures. Although the reason why the site is rich in new compounds is currently unknown, the researchers believe it may be because this specific area is exposed to limited human traffic.

Although none of the new compounds have proven to be a pathway to new antibiotics, one of the compounds discovered, called cabrillostatin, exhibits bioactivity and is being studied as a possible new approach for treating cancer and heart disease.

“The ocean is one of the least explored areas on the planet, especially the deep sea,” Chase said. “There is so much we don’t know about marine microorganisms and the compounds they produce. Due to antibiotic resistance and other health concerns, research into natural products is a top priority. With SMIRC, we now have an easily deployable system that allows researchers to study compounds that were previously inaccessible.”