Identification of Compounds with pH-Dependent Bactericidal Activity against Mycobacterium tuberculosis

@article{Early2019IdentificationOC,
  title={Identification of Compounds with pH-Dependent Bactericidal Activity against Mycobacterium tuberculosis},
  author={Julie V. Early and Juliane Ollinger and Crystal M. Darby and Torey Alling and Steven Francis Mullen and Allen C Casey and Ben Gold and Jason Ochoada and Todd R. Wiernicki and Thierry Masquelin and Carl F. Nathan and Philip Arthur Hipskind and Tanya Parish},
  journal={ACS Infectious Diseases},
  year={2019},
  volume={5},
  pages={272 - 280}
}
To find new inhibitors of Mycobacterium tuberculosis that have novel mechanisms of action, we miniaturized a high throughput screen to identify compounds that disrupt pH homeostasis. We adapted and validated a 384-well format assay to determine intrabacterial pH using a ratiometric green fluorescent protein. We screened 89000 small molecules under nonreplicating conditions and confirmed 556 hits that reduced intrabacterial pH (below pH 6.5). We selected five compounds that disrupt… Expand
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