Cal Poly scientists look to ancient microbes to discover the antibiotics of the future

A quest to discover new antibiotics is taking a Cal Poly biochemistry research team back in time millions of years as they study ancient microorganisms.  

Research led by Cal Poly biochemistry Professor Katharine Watts and Frost Teacher-Scholar Postdoctoral Fellow Rachel Johnson involves intensive study of a library of ancient microbial strains that are approximately 25 to 40 million years old.  

Cal Poly Professor Emeritus Raul Cano, who once worked with the scientist who inspired Michael Crichton’s “Jurassic Park,” donated his collection of 93 prehistoric bacteria strains to Watts for research. The collection includes strains extracted from amber, as well as other sources such as ocean floor sediment samples from the Gulf of Mexico.  

The Bailey College of Science and Mathematics team hopes the work will provide insights into potential benefits for modern medicine.  

“It’s extremely exciting to have this rare chance to work with a treasure trove of ancient bacteria, which could be very different from those living in the modern environment,” Watts said. “The majority of antibiotics on the market were originally discovered from bacteria that naturally produce them. Our goal is to screen which ancient strains may produce something like an antibiotic and then gather genomic information that can help us understand how it’s being made.”  

Their research comes amid the rise of antibiotic-resistant pathogens that can render medications ineffective in treating diseases such as pneumonia, urinary tract infections, sepsis, skin inflammations, foodborne illnesses and others. Many scientists are seeking new antibiotic molecules that could target pathogenic bacteria that have become resistant to existing drugs. The key could be investigating underexplored microbes, like those from the ancient library, for antibiotic production.  

Another goal of the research is to gain a deeper understanding of antibiotic resistance.   

“We’re also testing these ancient microbes for their ability to survive modern antibiotic compounds,” Johnson said. “Through these screenings, we can go back in history and ask, “What were they resistant to back then?” 

Scientists have successfully cultured over 30 microbes and are checking whether the compounds they make act as antibiotics against lab-safe bacteria that mimic disease-causing pathogens. 

The researchers have already identified seven strains of bacteria that exhibit antibacterial activity, but the chemical structures of the antibiotic molecules must still be determined. Another strain showed resistance against a known antibiotic, called apramycin, which is used in veterinary medicine to treat infections in animals. Bacteria protect themselves against antibiotics they produce; so it is possible that the strain produces apramycin or another closely related molecule. It may have evolved resistance against apramycin for another reason. Genetic analyses will help point to structures of these antibiotic compounds, as well as potential resistance mechanisms. 

The unusual opportunity arose because Cano collected the strains decades ago. Cano isolated microorganisms from the guts of bees and soil trapped in ancient amber, highlighted in a 2009 article in WIRED magazine that reported on his extractions from fossilized amber. Cano used ancient yeast as an ingredient in a craft beer that he called Fossil Fuels.  

Cano became interested in extracting DNA from fossils after working with George Poinar, an entomologist (focusing on study of insects) whose work inspired author Michael Crichton to publish the science-fiction novel “Jurassic Park” in 1990. In 1993, Cano and Poinar collaborated with other scientists to extract DNA from a 125-million-year-old Lebanese weevil (a small beetle with a long snout) preserved in amber. 

Cano’s collection includes over 40 different strains of bacteria from amber, which are stored at a temperature of negative 80 °C (−112 °F). The bacteria are grown near room temperature with traditional nutrients for modern lab bacteria for ongoing studies.  

The goal of the current Cal Poly research is to predict the types of molecules the strains might produce based on their genetic sequences. Antibiotics are small molecules that target or disrupt vital processes in harmful bacterial cells when used to treat in infection.   

While the Cal Poly team is in the research and discovery stages, there are currently no plans to design a drug, which would likely require significant additional financial investment and industry partnerships, as well as further scientific study. But the research could provide new structures for antibiotic development and clues into how resistance mechanisms arise.  

Student participants have been funded through the university’s BEACoN program, supporting underrepresented students in research. Cal Poly’s Research, Scholarly and Creative Activities Grants program has also provided student support as well as supplies and materials. 

“Working with bacteria strains from millions of years ago is surreal,” said Safiya Rufino, a microbiology major and a BEACoN Research Scholar. “These bacteria samples have lived during a time we can only know through carbon dating. It also makes me wonder how it would be to one day be revived millions of years in the future, how would I react, would I still be able to function as I once did as these bacteria are able to?” 

Microbiology major and BEACoN Research Scholar Kaitlyn Calligan added: “It’s really fun to have so many various strains of bacteria at our disposal. They include bright yellow, pink, matte white, or have interesting colony formations. Researching them truly is never boring.”