SUPER SPONGE
ECU researcher’s unexpected discovery in the Caribbean Sea could save lives
Dr. John Cavanagh was sitting in a collaborator’s office at the National Oceanic and Atmospheric Administration location in Charleston, S.C., in 2002 when a picture came onto a computer screen that changed his life – and potentially the lives people around the world.
The photograph was of a sea sponge, called Agelas conifera, that grows about 50 feet deep in the waters of the Caribbean Sea.
“When I looked at the picture of the sponge it was very clean and, in the ocean, everything else has dirt, crustaceans and algae all over it. I thought, ‘Why is this sponge clean when everything else around it is covered in bacteria and goop?’” recalled Cavanagh, chair of biochemistry and molecular biology at East Carolina University’s Brody School of Medicine.
For the next 17 years, Cavanagh – who came to ECU from North Carolina State University about a year ago – worked with a collaborator at the University of Notre Dame to figure out how the molecules produced by the sponge repel bacteria and if there were potential pharmaceutical benefits.
“We were just kind of shooting in the dark. We knew the molecules worked, but we didn’t know how,” Cavanagh said. “But within the last year or so, we discovered the mechanism of action, which means we now know exactly what these molecules target and what in the cells they target to stop the bacteria from working.”
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The researchers discovered that a molecule emitted from the sponge overcomes all of the ways bacteria resist antibiotics – thus making antibiotics more effective.
“The molecules from the sponge are able to shut down the ability of bacteria to communicate with each other and sense the outside world. It’s like putting earbuds in and blinders on so the bacteria can’t see anything and there’s no longer signaling between them – they’re unable to identify or resist the antibiotics,” Cavanagh said. “This technology that we’ve discovered has the opportunity to treat every kind of infection and break resistance of every type of nasty bacterium.”
THE THREAT
“One of the biggest things in the world going on at the moment, from a medical standpoint, is bacterial resistance – where the existing antibiotics no longer work. By the year 2050, they expect one person in every 3 seconds will die from of this,” Cavanagh said. “It is going to be worse than everything else put together.”
According to a United Nations report, drug-resistant diseases kill at least 700,000 people every year. But the report warned that if no action is taken, drug-resistant diseases could cause 10 million deaths annually by 2050 and have “catastrophic” economic damages on par with the 2008-2009 global financial crisis.
Researchers have been working for a long time to develop new antibiotics, Cavanagh said, but it takes about 12 years and about $1.5 billion to get an antibiotic onto the market – if everything goes right.
“Wouldn’t it be good if there were a way to make all of the old antibiotics work again?” Cavanagh asked. “We believe that’s what we’ve found.”
THE POTENTIAL
Dr. Morgan Milton, a postdoctoral scholar in Brody’s Department of Biochemistry and Molecular Biology, has been working on the research with Cavanagh for the past few years.
Cavanagh credits Milton for putting the pieces of his research together.
Milton uses structural biology techniques, such as X-ray crystallography, to solve three-dimensional structures of proteins that aid the researchers in understanding how the proteins they’re studying work.
ECU researchers say molecules from a sea sponge – called Agelas conifera, which grows about 50 feet deep in the waters of the Caribbean Sea – could make antibiotics more effective. (Courtesy of Twilight Zone Expedition Team 2007, NOAA-OE)
“I find it incredibly fascinating because, to me, it’s a puzzle. We know it works and we know it has some amazing properties. But how are some of these little compounds from a sea sponge doing this?” asked Milton, who is also the president of ECU’s Postdoctoral Association. “I have all of the pieces and I have a tool set to help me put these pieces together – can I figure it out? And we’re getting there.”
The researchers are able to synthesize the molecules from the sponge, so they don’t have to kill the sponges for research. And so far, these compounds have been enormously effective in overcoming bacterial resistance to antibiotics.
“We’ve tested at least 20 different bacteria and tons of different antibiotics,” Milton said. “It seems like with everything we test, it works either really well or at least decently.”
Cavanagh and Milton said the compounds work on every type of bacteria and their research has only begun to scratch the surface of their potential benefits.
“There is no resistance trait that they can’t break,” Cavanagh said. “They help literally everything.”
But some of the most recent discoveries of potential benefits have even surprised the researchers.
For example, while collaborating with staff at ECU’s School of Dental Medicine on treating mouth infections, they learned mouth inflammation from infections could lead to early onset of Alzheimer’s disease.
“We are very surprised that we now stand to work in the Alzheimer’s disease field,” Cavanagh said. “So we’re not just infectious disease people anymore. We’re actually working with the dental people to address inflammation and then hopefully, the early onset of Alzheimer’s.”
Dr. Morgan Milton and Dr. John Cavanagh. (Photo by Cliff Hollis)
Cavanagh said the researchers also “accidentally” found that some of the compounds from the sponge help cancer chemotherapeutics work better.
“In the infectious disease world, we can make some old antibiotics work about 4,000 times better, so you need 4,000 times less antibiotic to get the same effect. We recently found that one class of the molecules that we work with also seems to do that with cancer drugs too,” Cavanagh said.
“We’re very interested in working with pediatric cancers, because kids are much more sensitive to the amount of cancer chemotherapeutic. But if you can use a lot less of the chemotherapeutic to get the same effect, then we would like to help out with that too.”
The researchers have also been working with the U.S. military on some projects, including helping the Stealth Bomber be stealthier by using the molecules to remove the thin layer of biofilm bacteria that stick to the bombers and enable radar to detect them.
Their research also has immediate relevancy during the current COVID-19 crisis. With their weakened immune systems, a subset of COVID-19 patients develop secondary bacterial infections. One of the infections, known as A. baumanni, is notably multi-drug resistant and can cause septic shock, resulting in severe organ damage and death. Cavanagh said the researchers’ technology is “spectacularly good” against this type of infection.
“These molecules have almost limitless applications,” Cavanagh said. “What we’re doing has a direct impact on every person in the world.”
Cavanagh said the researchers very close to having the lead compounds that will go into Phase I clinical trials and that human patients could start realizing the benefits of this research in about seven years.
“We hit a home run with this if we get everything right,” he added.