The Wilson Lab has shown that orthosomycins bind to a site on the bacterial ribosome that is not used by any other antibiotic. The finding could lead to agents that are effective against existing multi-drug resistant bacterial strains.
Bacterial pathogens that have become resistant to several different classes of antibiotics, and for which no safe and effective alternative therapies are currently available, are a steadily growing problem. Hence there is already a pressing need for new antibacterial drugs. Biochemical investigations have suggested that compounds known as orthosomycins could provide the basis for the design of antibiotics with novel modes of action. In collaboration with teams led by Dr. Scott Blanchard at Cornell University (Ithaca, New York) and Dr. Yury Polikanov of the University of Illinois in Chicago, Stefan Arenz et al. have characterized the complexes formed by two orthosomycins with their target, and provided additional insights into their mechanism of action. The new findings, which appear in the latest issue of the journal PNAS, provide the basis for further optimization of these agents for use against multi-drug resistant bacterial strains.
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Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome.
Arenz S, Juette MF, Graf M, Nguyen F, Huter P, Polikanov YS, Blanchard SC, Wilson DN.
Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7527-32. doi: 10.1073/pnas.1604790113. Epub 2016 Jun 21. PMID: