Preventing 'cell wall remodeling' may hold key to defeating intransigent super bugs | 2/19/2019 | Staff
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B. multivorans is a notorious pathogen that can cause infections such as pneumonia in immune-compromised individuals with underlying lung diseases, including cystic fibrosis. This pathogen can also cause rapid clinical deterioration in patients, including blood stream infections, which can lead to death. What makes B. multivorans especially dangerous is that it is intrinsically resistant to a broad range of antibiotics, creating a major challenge to treatment.

Now, with a $3.34M grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, Edward W. Yu, Ph.D., professor of pharmacology at Case Western Reserve University School of Medicine, is conducting research that could help physicians better understand how bacteria such as B. multivorans resist antibiotics, potentially leading to improved treatments.

Yu - Colleagues - Robert - A - Bonomo

Yu and his colleagues, including Robert A. Bonomo, MD, professor of medicine, pharmacology, molecular biology and microbiology at CWRU, and chief of the medical service at Louis Stokes Cleveland VA Medical Center, will focus on describing the structure and function of cell-wall strengthening ("remodeling") machinery in B. multivorans and identifying peptide-based inhibitors to block this process, thus reducing the potential life-threatening activity of the bacteria.

Previously, Yu found that B. multivorans uses reinforced cell walls to thwart antibiotics. It does this by transporting lipid compounds—called hopanoids—from its inner cell membrane to its outer cell membrane, making the latter stronger and stiffer. This prevents antibiotics from doing their job by rendering the bacteria impregnable. "My goal is to disable the wall structures, allowing antibiotics to penetrate the bacteria and render it ineffective," he said.

Grant - Yu - Proteins - HpnN - HpnM

Under the new grant, Yu will target two proteins called HpnN and HpnM. Based on preliminary data, his hypothesis is...
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