Scripps Research Logo

News Release

Researchers Find Protein that Could Help Fight Antibiotic Resistance

LA JOLLA, Calif. & ANN ARBOR, Mich. – Nov. 2, 2017 –  Bacterial growth on medical devices—such as artificial hip implants, knee implants and catheters—are a major threat to patient health.

Now, investigators at The Scripps Research Institute (TSRI) and the University of Michigan (U-M), have found that a protein produced within the human body, not previously known to influence bacterial infections, could fight this problem. The team’s results were published recently in the journal Proceedings of the National Academy of Sciences.

When bacteria collect on a surface, such as a medical device, they form a protective layer called a "biofilm." These biofilms are held together by a scaffolding composed of a protein, called amyloid, produced by the bacteria.

In the case of implanted medical devices and catheters, biofilms protect bacterial colonies from the environment, including antibiotics a doctor might prescribe to attack the infection. In fact, a 2001 study found that 95 percent of urinary tract infections in critically ill patients were traced back to their catheters.

The researchers in the new study, led by Matthew Chapman, Ph.D., a U-M professor of molecular, cellular and developmental biology, and Joel Buxbaum, M.D., professor emeritus in the department of molecular medicine at TSRI, found that a protein produced by humans called transthyretin, or TTR, can suppress the formation of amyloid and biofilm in a particular strain of E. coli, a common cause of urinary tract infections in humans.

"One of the most important health implications for biofilms is on catheters. On any sort of device that you try to put in a human, a biofilm will form," Chapman said. "This is a huge, huge problem because even after being catheterized for just a few days, biofilm formation gives bacteria a chance to colonize the device, which can lead to serious infections that are difficult to eradicate."

The team studied how TTR interacted with a strain of E. coli found in human urinary tract infections. In UTIs, the bacterial strain settles into the bladder, forming biofilm communities. Bacteria in a biofilm encase themselves in a coat of amyloid fibers that help to protect them from stressors in the environment. E. coli amyloids are composed of a protein called CsgA. When the researchers mixed purified TTR and CsgA, they found that CsgA could not make protective amyloids. Further, when TTR was added to biofilm-forming bacterial colonies, biofilm formation was inhibited.

“It’s easier to break individual sticks rather than a bundle. Similarly, bacterial infections can be treated more effectively if bacteria are not held together in biofilms," said Neha Jain, lead author and a postdoctoral fellow in the Chapman lab. "We found that TTR can prevent biofilm formation in a uropathogenic E. coli strain, as well as other bacterial strains."

Taking down a bacteria's key defense against its environment could allow the body to fight the infection more effectively—or, Chapman said, allow physicians to prescribe a lower dose of antibiotics, or prescribe that a patient take antibiotics for a shorter period of time. This could help protect against the growing problem of antibiotic resistance.

"It's possible that products based on these protein interactions, if coated on susceptible surfaces prior to insertion or implantation in patients could reduce this problem considerably,” said Buxbaum, who has long studied TTR.

Chapman and Buxbaum say implementing this will require more research, but the move would be positive.

"These biofilms both make bacteria resistant to antibiotics and resistant to many of the host responses," Chapman said. "If you could target that resistance, the host may be able to clear the infection, or you could potentially prescribe lower doses of antibiotics or shorten the duration of antibiotic usage, which would all be good things."

The research also highlights an interesting aspect of molecular biology, Buxbaum added.

“As a biologic phenomenon, it is interesting that humans and bacteria have evolved in such a way that both express molecules with structures similar enough to interact in a biologically significant manner, even though they have quite different functions in their hosts,” said Buxbaum.

The new study, “Inhibition of curli assembly and Escherichia coli biofilm formation by the human systemic amyloid precursor transthyretin,” also included authors from Umeå University. The research was supported by the National Institutes of Health (grants R01-GM118651 and R01-AI099099), an Mcubed grant, the Protein Folding Disease Initiative, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Göran Gustafsson Foundation and the Swedish Foundation for Strategic Research.

Written by Morgan Sherburne, University of Michigan. Additional edits by Madeline McCurry-Schmidt, The Scripps Research Institute.

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see www.scripps.edu.

# # #

For information:
Office of Communications
Tel: 858-784-2666
Fax: 858-784-8118
press@scripps.edu


Joel Buxbaum, M.D., professor emeritus in the department of molecular medicine at TSRI (High-res image)


FOR MORE INFORMATION