ArticleACS chemical biology2015
Target-based screen against a periplasmic serine protease that regulates intrabacterial pH homeostasis in Mycobacterium tuberculosis.
Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- In-silico drug repositioning studies of Candida albicans Nitrogen permease reactivator 1 (Npr1) kinase.Scientific reports · 2025Article
- TargetingMicrobiology (Reading, England) · 2024Review
- Identification of cell wall synthesis inhibitors active against Mycobacterium tuberculosis by competitive activity-based protein profiling.Cell chemical biology · 2022Article
- AC2P20 selectively killsRSC advances · 2021Article
- The pursuit of mechanism of action: uncovering drug complexity in TB drug discovery.RSC chemical biology · 2021Article
- Acid Fasting: Modulation of Mycobacterium tuberculosis Metabolism at Acidic pH.Trends in microbiology · 2019Review
- Quantifying Acute Fuel and Respiration Dependent pH Homeostasis in Live Cells Using the mCherryTYG Mutant as a Fluorescence Lifetime Sensor.Analytical chemistry · 2019Article
- Mycobacterium smegmatis HtrA Blocks the Toxic Activity of a Putative Cell Wall Amidase.Cell reports · 2019Article
- Identification of Compounds with pH-Dependent Bactericidal Activity against Mycobacterium tuberculosis.ACS infectious diseases · 2019Article
- A high-throughput whole cell screen to identify inhibitors of Mycobacterium tuberculosis.PloS one · 2019Article
- Targeting the Proteostasis Network for Mycobacterial Drug Discovery.ACS infectious diseases · 2018Review
- Genetic and metabolic regulation of Mycobacterium tuberculosis acid growth arrest.Scientific reports · 2018Article
- Hit Generation in TB Drug Discovery: From Genome to Granuloma.Chemical reviews · 2018Review
- Article
- Targeting Phenotypically Tolerant Mycobacterium tuberculosis.Microbiology spectrum · 2017Review
- Article
- Systematic Survey of Serine Hydrolase Activity in Mycobacterium tuberculosis Defines Changes Associated with Persistence.Cell chemical biology · 2016Article
- Uncovering the Serine Hydrolytic Landscape of Mycobacterium tuberculosis.Cell chemical biology · 2016Article
- A Mycobacterium avium subsp. paratuberculosis Predicted Serine Protease Is Associated with Acid Stress and Intraphagosomal Survival.Frontiers in cellular and infection microbiology · 2016Article
- The Carbonic Anhydrase Inhibitor Ethoxzolamide Inhibits the Mycobacterium tuberculosis PhoPR Regulon and Esx-1 Secretion and Attenuates Virulence.Antimicrobial agents and chemotherapy · 2015Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
Mycobacterium tuberculosis (Mtb) maintains its intrabacterial pH (pHIB) near neutrality in the acidic environment of phagosomes within activated macrophages. A previously reported genetic screen revealed that Mtb loses this ability when the mycobacterial acid resistance protease (marP) gene is disrupted. In the present study, a high throughput screen (HTS) of compounds against the protease domain of MarP identified benzoxazinones as inhibitors of MarP. A potent benzoxazinone, BO43 (6-chloro-2-(2'-methylphenyl)-4H-1,3-benzoxazin-4-one), acylated MarP and lowered Mtb's pHIB and survival during incubation at pH 4.5. BO43 had similar effects on MarP-deficient Mtb, suggesting the existence of additional target(s). Reaction of an alkynyl-benzoxazinone, BO43T, with Mycobacterium bovis variant bacille Calmette-Guérin (BCG) followed by click chemistry with azido-biotin identified both the MarP homologue and the high temperature requirement A1 (HtrA1) homologue, an essential protein. Thus, the chemical probe identified through a target-based screen not only reacted with its intended target in the intact cells but also implicated an additional enzyme that had eluded a genetic screen biased against essential genes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.