With antibiotic-resistance spreading at a dire rate, novel treatments are desperately needed to manage the 3 million yearly infections in the U.S. alone. And while novel is usually synonymous with “new,” scientists at the University of Minnesota are searching in the opposite direction—they’re looking for solutions in fossils of the long-dead.
“Fossils can be an unexpected source of new chemical matter. The compounds you obtain undergo biotransformations over millions of years. That gradual series of reactions can lead to novel structures that we haven’t seen before. These compounds are from species that are now extinct, so their biochemical pathways often vary from ones we see today,” said Elizabeth Ambrose, a professor in the Department of Medicinal Chemistry at University of Minnesota.
Ambrose and graduate student Connor McDermott decided to focus on the medicinal purposes of Baltic amber, as the fossil resin has long been renowned in folk medicine for its anti-inflammatory and anti-infective properties.
In their most recent project, the scientists analyzed commercially available Baltic amber samples, as well as some Ambrose herself collected while visiting family in Lithuania. The Baltic Sea region contains the world’s largest deposit of amber, fossilized about 44 million years ago. The resin oozed from now-extinct pines in the Sciadopityaceae family and acted as a defense against microorganisms, such as bacteria and fungi, as well as herbivorous insects.
For the experimental portion of the study, McDermott said he used a tabletop jar rolling mill to turn the amber pebbles into a homogenous fine powder that could be extracted. Semi-fine powder in hand, McDermott used various solvents and techniques to filter, concentrate and analyze the amber powder extracts by gas chromatography-mass spectrometry (GC-MS).
While dozens of bioactive compounds were identified in the spectra, three stood out—abietic acid, dehydroabietic acid and palustric acid. The researchers then bought pure samples of the compounds and tested their activity against nine bacterial species, some of which are known to be antibiotic-resistant. They found the compounds to be active against gram-positive bacteria—including MRSA—but not gram-negative bacteria.
“This implies that the composition of the bacterial membrane is important for the activity of the compounds,” explained McDermott.
Interestingly, McDermott was able to get his hands on a Japanese umbrella pine tree, the closest living species to the ancient version that produced the Baltic amber resin. Extracting resin from the needles and stem, McDermott identified sclarene, a molecule that could theoretically undergo the chemical transformations necessary to produce abietic acid.
“There are hundreds to thousands of abietic acid analogues in the extracts [McDermott] found,” said Ambrose during her presentation at the spring meeting of the American Chemical Society (ACS). “They are structurally very similar and difficult to break out; but, it’s a treasure trove of abietic acid analogues and aviates that we haven’t seen anywhere else. It’s unique.”
The chemistry professor pointed to pain, inflammation and infectious disease as three key modalities urgently in need of drug scaffolds. She believes abietic acids and their deriv7656atives could potentially fill this role.
“Baltic amber is really only the beginning, and the compounds we’re looking at in Baltic amber are really only the beginning,” said ambrose. “There’s a lot more work to be done but we really need to start looking at paleopharmaceuticals and these unexpected sources because we’re in dire need of new scaffolds for key disease modalities.”
Photo: Baltic amber could be a potential source of new antibiotics. Credit: Connor McDermott