Greensboro Firm Develops Crab Ranch To Corral Drug Resistant Bacteria

Kepley BioSystems logo

A ranch for horseshoe crabs could soon help corral drug resistant bacteria. 

It’s the brainchild of a life science team at Greensboro-based Kepley BioSystems (KBI). The project, which began with a $5,000 subsidy from North Carolina Sea Grant, recently got a big boost—$225,000 in Phase 1 feasibility funding from the National Science Foundation. 

Horseshoe crabs, as it turns out, make a crucial contribution to public health. Their blue blood contains Limulus amebocyte lysate (LAL). It’s a liquid extract of blood cells vital to the crustacean’s immune system. Researchers have discovered that LAL can be used to provide one of the most accurate ways to identify E. coli, salmonella and other dangerous endotoxins. LAL clots when exposed to even minuscule levels of life-threatening gram-negative bacteria, a major contributor to antibiotic resistance.

As a result, close to 600,000 horseshoe crabs are captured from the Atlantic seaboard each year so their blood can be harvested for LAL. The substance is used primarily to test the sterility of drugs and medical devices. 

While most of the crabs are returned to their natural habitat, an estimated 30 percent don’t survive the experience. Add to that a similar number that are captured and used for fishing bait and you begin to threaten the viability of an ancient species that has been around for more than 450 million years. 

Horseshoe crab
Horseshoe crab. -- Kepley BioSystems photos

That’s where Kepley BioSystems’ Horseshoe Crab Ranch and Blood Institute enters the picture. The company plans to develop either a recirculating aquaculture system similar to a commercial fish farm, or a protected estuary. Both options can provide a friendly and tightly controlled environment for horseshoe crabs. There they can be fed, monitored and carefully bled for LAL to minimize the impact on their well being. 

By creating the ideal diet and water quality for these crabs, and by reducing physiological and environmental stress, researchers hope to improve survival rates. The end game is to establish an ecosystem that can preserve the health of horseshoe crabs while eliminating the need to capture them in the wild. It’s an idea that makes perfect sense, but it’s never been tried before.

“We’re still very early into our research,” said Kepley BioSystems Principal Investigator Kristen Dellinger, Ph.D. “We’ll spend the next six months setting up protocols, acclimating and monitoring a small number of crabs—somewhere between 30 and 100—and refining the process we’ll use to bleed them.” If all goes well in phase I, Dellinger said the company will apply for a $750,000 Phase 2 National Science Foundation grant to continue its research, expand and improve LAL production, and begin to commercialize the project. The second phase is expected to last two to three years.

Kepley BioSystems Principal Investigator Kristen Dellinger, Ph.D. (left) assisted by Jordan Gannon
Kepley BioSystems Principal Investigator Kristen Dellinger, Ph.D. (left)
assisted by Jordan Gannon in examining a horseshoe crab

Dellinger and her project team are working with the state of Georgia to find a suitable saltwater estuary where horseshoe crabs native to that area can live in their natural environment. In tandem with the estuary, Kepley will operate an aquaculture system adjacent to its Greensboro facilities.

The stakes couldn’t be much higher. The LAL in horseshoe crabs is the best mechanism available to rapidly detect gram-negative bacteria. That’s important because antibiotic resistance to these microorganisms has dramatically increased on a global scale. 

The World Health Organization reports that 10 of the 14 most virulent drug resistant bacteria are gram-negative. And the Centers for Disease Control and Prevention considers antibiotic resistance one of today’s biggest public health challenges. Each year at least two million people in the United States alone get an antibiotic-resistant infection and more than 23,000 die. So early detection is crucial.

KBI President Anthony Dellinger, Ph.D.
KBI President Anthony Dellinger, Ph.D.

“The successful ranching of horseshoe crabs also could provide and almost unlimited supply of LAL that would address another global health challenge,” said KBI President Anthony Dellinger, Ph.D. The parts-per-trillion sensitivity of LAL testing—and the speed with which results are available—could eventually open the door to bedside screening for asymptomatic septicemia – the early stage of a serious bacterial bloodstream infection, also called blood poisoning. And that could mean early intervention and treatment of two out of every three hospital acquired infections. This proactive approach could reduce the risk from “superbugs” by treating infections before they overwhelm the antibiotics used to manage them. 

In addition, there are significant environmental benefits. The population levels of the Atlantic horseshoe crab impact many other native species. The Red Knot bird, for example, depends on the egg-laying cycles of the crabs for food. When the horseshoe crab population declines, so do the Red Knots, which are now on the U.S. Endangered Species Act’s “threatened” list.

“We have a really good idea of what needs to be done,” Anthony Dellinger said. “And we think that, given the urgency of the situation and the need for what this project can deliver, it will be well received as we move forward.”

Companion projects underway

Kepley isn’t only focused on horseshoe crabs. Two other innovative coastal projects also are under development: 

  • An environmentally friendly synthetic bait for lobster and crab fisheries.
  • Similarly eco-friendly synthetic horseshoe crab eggs that can provide a nutritional supplement for migrating shorebirds.

OrganoBait, a fully synthetic lure made without fish or animal byproducts, mimics the odor of dead and decaying fish that attracts crustaceans. It’s easier to buy, store and use than the herring, menhaden, anchovies, and mackerel that fishermen have relied on for centuries to bait lobster and crab traps. 

Just as important, OrganoBait could help relieve overharvesting of the forage fish eaten by larger fish, birds and mammals. About 40 billion pounds of these fish are used each year to catch crustaceans. That’s a $20 billion market that accounts for at least a third of the annual global harvest. Declining stocks of forage fish can disrupt the ocean ecosystem, depriving sea birds, whales, sea turtles, dolphins, seals and fish of a crucial food source.

Kepley also is developing synthetic feed to mimic the horseshoe crab eggs that are a food source for migrating Red Knots and other shorebirds. These “eggs” will serve as a nutritional supplement at flyover beaches where horseshoe crab populations have declined sharply.

About Kepley BioSystems

Ph.D. scientist Christopher Kepley and corporate advisor Terry Brady founded Kepley BioSystems in 2013. Anthony Dellinger, a Ph.D. nonoscientist, is the organization’s president. 

The company operates out of Gateway University Research Park in Greensboro in collaboration with the Joint School of Nanoscience and Nanoengineering, a partnership between the North Carolina Agriculture and Technical State University and the University of North Carolina at Greensboro. 

Kepley BioSystems’ mission is to develop disruptive innovations to achieve global solutions.

Bryant Haskins, NCBiotech Writer
Fri, 10/12/2018 - 11:24