ArticleACS infectious diseases2019
Identification of Compounds with pH-Dependent Bactericidal Activity against Mycobacterium tuberculosis.
Article in ACS infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed.
- Integrating chemical, genetic, and feasibility assessments for anti-tubercular target validation.EMBO molecular medicine · 2026Review
- Common Biological Properties ofACS infectious diseases · 2025Article
- Unraveling Mycobacterium tuberculosis acid resistance and pH homeostasis mechanisms.FEBS letters · 2025Review
- Antitubercular potential and pH-driven mode of action of salicylic acid derivatives.FEBS open bio · 2025Article
- TargetingMicrobiology (Reading, England) · 2024Review
- Combination of gallium citrate and levofloxacin induces a distinct metabolome profile and enhances growth inhibition of multidrug-resistantFrontiers in microbiology · 2024Article
- Identification of 2-Amino Benzothiazoles with Bactericidal Activity against Mycobacterium tuberculosis.Microbiology spectrum · 2023Article
- Anti-tuberculosis treatment strategies and drug development: challenges and priorities.Nature reviews. Microbiology · 2022Review
- Discovery of a novel type IIb RelBE toxin-antitoxin system in Mycobacterium tuberculosis defined by co-regulation with an antisense RNA.Molecular microbiology · 2022Article
- New Potential Pharmacological Targets of Plant-Derived Hydroxyanthraquinones fromMolecules (Basel, Switzerland) · 2022Article
- Article
- Tools to develop antibiotic combinations that target drug tolerance inFrontiers in cellular and infection microbiology · 2022Review
- AC2P20 selectively killsRSC advances · 2021Article
- Handling the Hurdles on the Way to Anti-tuberculosis Drug Development.Frontiers in chemistry · 2020Review
- Acid Fasting: Modulation of Mycobacterium tuberculosis Metabolism at Acidic pH.Trends in microbiology · 2019Review
- Review
- Anthranilic amide and imidazobenzothiadiazole compounds disruptMedChemComm · 2019Article
- NSC 18725, a Pyrazole Derivative Inhibits Growth of IntracellularFrontiers in microbiology · 2019Article
- Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
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 intrabacterial pH homeostasis and also showed some activity against nonreplicating bacteria in a 4-stress model, but with no (or greatly reduced) activity against replicating bacteria. The compounds selected were two benzamide sulfonamides, a benzothiadiazole, a bissulfone, and a thiadiazole, none of which are known antibacterial agents. All of these five compounds demonstrated bactericidal activity against nonreplicating bacteria in buffer. Four of the five compounds demonstrated increased activity under low pH conditions. None of the five compounds acted as ionophores or as general disrupters of membrane potential. These compounds are useful starting points for work to elucidate their mechanism of action and their utility for drug discovery.
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Registered trials
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