Anti-Biofilms Show Promise Against Common Drug-Resistant Bacteria

A newly discovered class of anti-biofilm compounds derived from marine microorganisms appears to show promise against a drug-resistant bacterium commonly associated with hospital-acquired infections, according to a study from researchers at the University of Michigan Life Sciences Institute and School of Public Health.

Published in the February 16 issue of Nature Communications, the study found that the new compounds, called cathuitamycins, were able to prevent the Acinetobacter baumannii bacteria from gathering as a biofilm in cell cultures. The finding is encouraging, given the ability of biofilms to cling to surfaces and form complex structures, making them much more resistant to antimicrobials when compared with free-floating bacteria.

With no drugs currently available or in clinical trials that specifically target biofilm formation, the cathuitamycins may present a future approach to attacking these biofilms that can cling to medical devices, prosthetic implants, and other surfaces all while being resistant to sterilization with standard antimicrobials.

“This is why preventing biofilm formation is such an important research target,” said co-lead author Ashootosh Tripathi, PhD, a research fellow in the lab of University of Michigan Life Sciences Institute faculty member David Sherman, PhD. Tripathi and colleagues conducted the study, given the growing worldwide concern of A. baumannii’s resistance to front-line antibiotics and ease with which it can form a biofilm. This is was makes treatment even more challenging, according to co-senior author Chuanwu Xi, PhD, associate professor of environmental health sciences at the University of Michigan School of Public Health.

The researchers discovered the new cathuitamycins by conducting high-throughput screening of compounds in the University of Michigan Life Sciences Institute library of “natural product” extracts. The library includes thousands of drug-like substance derived from marine microorganisms that Sherman and his collaborators collected during marine field collection expeditions throughout the world.

The new cathuitamycins were derived from Streptomyces gandocaensis, a bacterium that was isolated from marine sediment collected on a 2007 expedition to Punta Mona Island in Cost Rica. The research team found an extract that inhibited A. bumannii’s ability to form biofilms and then experimented to identify its most potent forms as well as create two new, more-potent analogs.

“This new class of biofilm inhibitors provides a foundation toward the development of safe and effective drugs to limit or prevent biofilm formation,” said Sherman, co-senior author of the study, Hans W. Vahlteich Professor of Medicinal Chemistry, and associate dean for research and graduate education at the University of Michigan College of Pharmacy, as well as professor of chemistry in the College of Literature, Science, and the Arts, and of microbiology and immunology in the Medical School. “As antibiotic resistance becomes an increasingly important global health concern, marine microorganisms have a great—and largely untapped—potential to provide new classes of antibiotics and anti-biofilm compounds.”