Biologists are gathering samples from the oceans with a technique called SMIRC, which may lead to the discovery of new compounds for next-generation antibiotics.
Growing up, SMU researcher Alexander Chase was captivated by the incredible variety of plants found in the tropical rainforests. This fascination led him to wonder what undiscovered species might be out there. Today, that same curiosity drives Chase to collect ocean samples using a novel approach known as Small Molecule In situ Resin Capture (SMIRC), potentially opening the door to new antibiotics.
Microbial natural products originate from microorganisms, often referred to as microbes. These tiny organisms are responsible for producing many critical medicines, including the majority of antibiotics available today. Because microbes are microscopic, they generate a range of chemical compounds throughout their life cycles, some of which can be beneficial for medical applications. Traditional methods for discovering these compounds involve a ‘microbe-first’ approach where researchers grow individual strains of microbes in the lab after collecting samples from the wild.
While this method has yielded valuable results, it has become increasingly challenging for scientists to find new chemical “scaffolds,” the foundational structures for creating chemical compounds. These scaffolds are essential for drug development.
“Currently, when we take new samples and cultivate the microbes, we’re mostly finding scaffolds that are very similar to those we’ve already identified,” says Chase, who is an assistant professor in the Roy M. Huffington Department of Earth Sciences. “Over the past few decades, it’s become harder to discover novel compounds using the ‘microbe-first’ strategy, which limits us to familiar bacterial strains and their corresponding chemical compounds that represent only a small fraction of the natural variety in the oceans. That’s where SMIRC becomes crucial, allowing us to venture into the unknown.”
A recent study published in the journal Nature Communications by Chase and collaborators from the University of California San Diego and University of California San Francisco highlighted how SMIRC enables the collection of microbial natural products directly in their natural environment, eliminating the need for lab cultivation. The research utilized an absorbent resin known as HP-20 that effectively captures the chemicals released by microbes.
As an initial test, the team applied SMIRC in seagrass areas close to San Diego. They successfully extracted an antibiotic compound and another chemical, chrysoeriol, a plant-derived substance known for its antibacterial properties. They later modified the SMIRC technique by combining HP-20 with agar, a growth-supporting substance for microbes. This adaptation uncovered aplysiopsene A, demonstrating the effectiveness of SMIRC for identifying valuable compounds.
A third experiment conducted in a protected marine reserve at Cabrillo National Monument yielded larger samples consisting of more intricate chemical mixtures. Although the exact reason this location produced a wealth of novel compounds remains unclear, the researchers suggest it may be linked to the area’s minimal human interference.
Although the new compounds identified thus far do not appear to pave the way for new antibiotics, one compound, named cabrillostatin, exhibits bioactivity and is being explored as a potential treatment for cancer and heart conditions.
“The ocean is one of the least explored regions on our planet, particularly the deep ocean,” stated Chase. “We still have so much to learn about marine microorganisms and the compounds they generate. Given the pressing issues of antibiotic resistance and other health challenges, research into natural products is critically important. SMIRC provides us with a straightforward system for examining compounds that were previously beyond our reach.”
