Novel Antimicrobials from Uncultured Bacteria Acting against Mycobacterium tuberculosis
Jeffrey Quigley, Aaron J. Peoples, Asel A. Sarybaeva, Dallas E. Hughes, Meghan Ghiglieri, Catherine Achorn, Alysha Desrosiers, Cintia R. Felix, Libang Liang, Stephanie Malveira, William P. Millett, Anthony Nitti, Baldwin Tran, Ashley M. Zullo, Clemens Anklin, Amy L. Spoering, Losee L. Ling, Kim Lewis
Abstract
Decreasing discovery rates and increasing resistance have underscored the need for novel therapeutic options to treat Mycobacterium tuberculosis infection. Here, we screen extracts from previously uncultured soil microbes for specific activity against Mycobacterium tuberculosis , identifying three novel compounds. We further define the mechanism of action of one compound, amycobactin, and demonstrate that it inhibits protein secretion through the Sec translocation machinery.