Maxamycins: Durable Antibiotics Derived by Rational Redesign of Vancomycin

Since its discovery, vancomycin has been used in the clinic for >60 years. Because of their durability, vancomycin and related glycopeptides serve as the antibiotics of last resort for the treatment of protracted bacterial infections of resistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus(MRSA) and multidrug-resistant (MDR) Streptococcus pneumoniae. After 30 years of use, vancomycin resistance was first observed and is now widespread in enterococci and more recently in S. aureus. The widespread prevalence of vancomycin-resistant enterococci (VRE) and the emergence of vancomycin-resistant S. aureus(VRSA) represent a call to focus on the challenge of resistance, highlight the need for new therapeutics, and provide the inspiration for the design of more durable antibiotics less prone to bacterial resistance than even vancomycin.