Dartmouth Study Highlights Substantial Role Of Genes, Biofilms In Bacterial Resistance-Research, Sponsored by Microbia, Inc., Identifies New Targets for Anti-Infective Drug Development

Hanover, NH-Common pathogenic bacteria appear to be genetically "programmed" to resist antibiotics, according to research by Dartmouth Medical School investigators presented today at the Fifteenth Annual North American Cystic Fibrosis Conference in Orlando. The study describes an intrinsic genetic mechanism closely linked to the organisms' "biofilm" that may play a major role in many failures of antibiotics. The Dartmouth study utilized a proprietary, high-throughput mutant-detection technology, applicable to all types of microorganisms, exclusively licensed by Microbia, Inc., a Cambridge, MA-based biotechnology company.

Biofilms are complex communities of bacterial cells that allow them to survive various environmental stresses such as antibiotics. These structures can form on industrial equipment, medical implants, teeth (plaque) and internal organs, and are estimated to be involved in 65 percent of human bacterial infections, according to the Centers for Disease Control and Prevention. Biofilms are implicated in medical implant infections, periodontal disease, pneumonias associated with cystic fibrosis, and infections of the middle ear. Conventional antibiotic therapy is usually effective against circulating bacteria but is frequently ineffective in treating biofilm sources of these pathogens: These surface-attached communities are up to 1,000-fold more resistant to antibiotics.

The study was designed to identify genes responsible for the antimicrobial resistance of biofilm bacteria. "This study sheds more light on the highly significant role played by biofilms in bacterial resistance to antibiotic therapy, and may suggest new directions for anti-infective research," said George O'Toole, PhD, assistant professor of microbiology and immunology at Dartmouth Medical School and study author. "These particular genetic mechanisms underlying this resistance have never before been uncovered, and we expect it will lead to substantial numbers of highly valuable genomic targets for researchers in this field.

"Our research further demonstrates that biofilms activate a specific genetic program that guides bacteria to develop increased resistance," said O'Toole. "Since the architecture of the mutant bacterial biofilms and the resistant biofilms were identical, our research contradicts a widely held theory that increased resistance is due merely to complex biofilm architecture."

The next step is to characterize the genes to reveal the biological mechanisms underlying how the biofilm bacteria increase resistance, said O'Toole.

"The Dartmouth study provides the first clues about the mechanisms underlying the resistance of biofilms to conventional antibiotic therapies. The data will also help to identify a new class of targets for the development of novel biofilm inhibitors, which may be used to boost the effectiveness of antibiotics," said Peter Hecht, PhD, CEO and a founder of Microbia.

The Company envisions that this new class of bacterial biofilm inhibitors would be administered concomitantly with existing antibiotics to significantly potentiate the action of those drugs, according to Hecht.

"Minimizing antibiotic use, and developing compounds with new targets and new modes of action, are basic approaches to overcoming bacterial resistance," said Hecht. "Development of bacterial biofilm inhibitors will help accomplish both objectives."

Thien-Fah Mah, PhD, a postdoctoral fellow at Dartmouth Medical School, is the principal author of the study. O'Toole, a Pew Biomedical Scholar, is a recognized pioneer and expert in the molecular and genetic basis of bacterial biofilm formation. He is a co-inventor on three biofilm patents exclusively licensed to Microbia by Harvard Medical School and Dartmouth College.

For more information, contact Bart Henderson, Microbia, Inc. (617) 456-3600. For more, see www.microbia.com.

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