Multivalent antibiotics for Gram-positive bacterial infections

Benzoic acid–based multivalent antibiotics could help treat Gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA), by inhibiting lipid carrier recycling necessary for cell wall biosynthesis.

A structure-activity screen identified eight multivalent molecules with antibacterial activity against wild-type and drug-resistant Gram-positive, but not Gram-negative, pathogens. The most potent compound, composed of a nitrogen core and three arms of 4-phenylbenzoic acid, reduced bacterial growth with minimum inhibitory concentrations (MICs) of 0.016 µg/mL for MRSA, 0.016 µg/mL for methicillin-resistant Staphylococcus epidermidis, 0.125 µg/mL for multi-drug resistant Staphylococcus haemolyticus, and 1 µg/mL for vancomycin-resistant Enterococcus faecium, and did not induce cytotoxicity in mammalian cells. ...