Fishing for Superbug and Seafood Safety

If you have been avoiding shellfish since that brutal attack of gastroenteritis after eating oysters on the halfshell, you may be assuming you are allergic to the tasty delicacies. More likely, you experienced an attack of Vibrio parahaemolyticus, a bacterial infection that is the leading cause of seafood gastroenteritis in the U.S. Alternatively, it may have been its cousin, Vibrio vulnificus, which causes severe septicemia, has a hospitalization rate of 91%, and is responsible for 95% of U.S. seafood deaths.

“These compounds appear to be effective against not only Vibrio, but also several other drug-and immunity- resistant bacteria.”

Vibrio species in the U.S. cause a minimum of 41,000 illnesses yearly, increasing during natural disasters involving flooding. Following Hurricane Katrina, 17 cases of Vibrio vulnificus were seen—five of them fatal.

Dr. John Cavanagh, professor of molecular and structural biochemistry, and Dr. Christian Melander, assistant professor of chemistry, are leading a project taking a systems biology approach to stopping Vibrio infections. “The project’s strengths come from integrating high-throughput comparative genomics methods, state-of-the-art structural biology, computational studies, and drug design strategies,” says Cavanagh. Comparative genomics efforts at the National Oceanic and Atmospheric Administration’s Hollings Marine Laboratory will provide information about which gene signal pathways are responsible for Vibrio virulence, persistence, and adaptability. Cavanagh’s structural biology studies will then examine those pathways in detail, providing therapeutic targets for Melander’s team of drug synthetic chemists to exploit.

The virulence and persistence of Vibrio are due to its ability to form biofilms—communities of bacteria that respond differently than a single bacterium to ensure survival in hostile and shifting environments. In the biofilm form, Vibrio can be up to 10,000 times more resistant to antibiotics, as well as inherently resistant to immune response.

Melander’s research group has discovered a class of chemical compounds that inhibit biofilm formation. “These compounds appear to be effective against not only Vibrio, but also several other drug-and immunity-resistant bacteria,” says Melander. Such “superbugs” include: Haemophilus influenzae (ear, eye, and respiratory tract infections); Bordatella pertussis (whooping cough); Acinetobacter baumannii (frequently found in hospitals, infecting patients through open wounds, catheters, and breathing tubes); and Pseudomonas aeruginosa (opportunistic infections of immuno-compromised individuals, including cancer and cystic fibrosis patients).

Melander and Cavanagh have a patent pending on the compounds and their uses, and have incorporated Agile Sciences, Inc. With angel investor backing, the start-up company will further develop the product, recruit drug company partners, and advance products to clinical trials. The eventual products will treat surfaces where the target bacteria lurk, including hospitals, medical devices, ships, seafood processing equipment—and maybe even that oyster bar you’ve been avoiding.

 

Drs. John Cavanagh and Christian Melander analyze results of an anti-biofilm screening test.

Drs. John Cavanagh and Christian Melander analyze results of an anti-biofilm screening test.

Vibrio bacteria.

Vibrio bacteria.

Gram staining protocol showing
amount of biofilms remaining 
after treating with antibiofilm
compounds. Light purple color 
in lower right indicates almost total elimination of biofilm.

Gram staining protocol showing amount of biofilms remaining after treating with antibiofilm compounds. Light purple color in lower right indicates almost total elimination of biofilm.