Identification of Nitroxoline and Halogenated Quinoline Analogues with Antibacterial Activities against Plant Pathogens

Bacterial pathogens that infect and kill plants are responsible for major crop damage (e.g. citrus canker). As is the case with human pathogens, bacterial species which are invasive to plants acquire resistance to common crop-bactericidal agents. Herein we report the identification of nitroxoline and simple halogenated quinoline (HQ) antibacterial agents that demonstrate antibacterial activities against a panel of plant pathogens, including Xanthomonas citri and Burkholderia andropogonis. A subset of active analogues was identified from an in-house library of 36 nitrogen-containing heterocycles which our group previously evaluated against multiple human pathogenic bacteria (e.g., Staphylococcus aureus). In this report, we also demonstrate that the phytochemical gallic acid (GA) potentiates the antibacterial activity of select halogenated quinolines against multiple Xanthomonas strains, including Xcc 306. We also show that nitroxoline and HQ 1 alone and in combination with GA inhibit Xcc 306 infection in a plant model, demonstrating the potential these compounds have as crop-bactericidal agents.