Therapeutics For Drug Resistant-Bacteria: Arylpropionyl-Phloroglucinols

Project Details


In preliminary work, we have identified a novel class of broad-spectrum antibacterial agents: arylpropionyl phloroglucinols (APPs). APPs potently inhibit bacterial RNA polymerase (RNAP)~but not mammalian RNAP~in vitro, potently inhibit bacterial growth in culture, and potently clear infection in a mouse model of methicillin-resistant Staphylococcus aureus infection. APPs exhibit antibacterial activity against both Gram-positive and Gram-negative bacterial pathogens, including drug-sensitive, beta-lactam-resistant, macrolide-resistant, tetracycline-resistant, rifampin-resistant, vancomycin-resistant, and multi-drug-resistant Staphylococcus aureus, Enterococcus faecalis, NIAID category A pathogen Bacillus anthracis, NIAID category A pathogen Francisella tularensis, and NIAID category B pathogen Brucella melitensis. APPs exhibit no cross-resistance with rifampin, the RNAP inhibitor in current use in broad-spectrum antibacterial therapy, and exhibit a spontaneous resistance rate
Effective start/end date4/25/143/31/18


  • National Institutes of Health (NIH)

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