(Philadelphia, PA) In todays online early edition of the Proceedings of the National Academy of Sciences, researchers at the University of Pennsylvania School of Medicine describe how one antibiotic currently under Phase III clinical testing, ramoplanin, works on the molecular level to disrupt the ability of bacteria to build cell walls. The researchers believe that lessons learned from ramoplanin may aid in developing new classes of antibiotics for treatment of antimicrobial resistance.
Ramoplanin is more effective than front line antibiotics such as vancomycin. In comparison to vancomycin, ramoplanins relatively simplistic chemical architecture lends itself well to chemical synthesis and modification qualities highly desirable for drug development, said Dewey G. McCafferty, PhD, assistant professor in Penns Department of Biochemistry and Biophysics. More importantly, ramoplanin dodges the problems of antibiotic resistance by attacking the bacteria in a spot that cannot be easily overcome by normal mechanisms of mutational resistance.
The ability of bacteria to acquire resistance to antibiotics stands testament to the ingenuity of evolution and, perhaps, to the overuse of bacteria-killing drugs. In a sense, antibiotics replace natural selection in driving changes in bacteria, as the survival of a single resistant cell can lead to whole new population of resistant bacteria. Distressingly, bacteria have grown resistant to vancomycin, the antibiotic of last resort for more than 30 years. Ramoplanin, however, has been found to be up to ten times as powerful as vancomycin and no resistance to the antibiotic has been reported to date.
Ramoplanin and vancomycin both attack the ability of bacteria to cross link together cell wall building blocks to form peptidoglycan, the large polymer made of sugars and amino acids that provides mechanical strength for the bacteria cell wall. Bacteria treated with ramoplanin or vancomycin form weakened cell walls that
Contact: Greg Lester
University of Pennsylvania School of Medicine