ArticleThe Journal of antimicrobial chemotherapy2010
Targeting the chromosome partitioning protein ParA in tuberculosis drug discovery.
Article in The Journal of antimicrobial chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Inhibitor of Chromosome Segregation inACS chemical biology · 2024Article
- ABT-MPNN: an atom-bond transformer-based message-passing neural network for molecular property prediction.Journal of cheminformatics · 2023Article
- Union Is Strength: Target-Based and Whole-Cell High-Throughput Screens in Antibacterial Discovery.Journal of bacteriology · 2022Review
- Deep learning-driven prediction of drug mechanism of action from large-scale chemical-genetic interaction profiles.Journal of cheminformatics · 2022Article
- Bioinformatic Exploration of Metal-Binding Proteome of Zoonotic PathogenFrontiers in genetics · 2019Article
- Hit Generation in TB Drug Discovery: From Genome to Granuloma.Chemical reviews · 2018Review
- Analysis of ParAB dynamics in mycobacteria shows active movement of ParB and differential inheritance of ParA.PloS one · 2018Article
- Global proteomic profiling of Yersinia ruckeri strains.Veterinary research · 2017Article
- Identification of Mycobacterial Genes Involved in Antibiotic Sensitivity: Implications for the Treatment of Tuberculosis with β-Lactam-Containing Regimens.Antimicrobial agents and chemotherapy · 2017Article
- Protecting Mammalian Hair Cells from Aminoglycoside-Toxicity: Assessing Phenoxybenzamine's Potential.Frontiers in cellular neuroscience · 2017Article
- Mycobacterial Growth.Cold Spring Harbor perspectives in medicine · 2015Review
- Article
- Regulated Expression Systems for Mycobacteria and Their Applications.Microbiology spectrum · 2014Article
- Comparative genomic analysis of Mycobacterium tuberculosis drug resistant strains from Russia.PloS one · 2013Article
- Antisense RNA regulation and application in the development of novel antibiotics to combat multidrug resistant bacteria.Science progress · 2013Review
- Characterization of a conserved interaction between DNA glycosylase and ParA in Mycobacterium smegmatis and M. tuberculosis.PloS one · 2012Article
- The internal organization of mycobacterial partition assembly: does the DNA wrap a protein core?PloS one · 2012Article
- A combined global and local approach to elucidate spatial organization of the Mycobacterial ParB-parS partition assembly.Biochemistry · 2011Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
objectiveTo identify inhibitors of the essential chromosome partitioning protein ParA that are active against Mycobacterium tuberculosis.
methodsAntisense expression of the parA orthologue MSMEG_6939 was induced on the Mycobacterium smegmatis background. Screening of synthetic chemical libraries was performed to identify compounds with higher anti-mycobacterial activity in the presence of parA antisense. Differentially active compounds were validated for specific inhibition of purified ParA protein from M. tuberculosis (Rv3918c). ParA inhibitors were then characterized for their activity towards M. tuberculosis in vitro.
resultsUnder a number of culture conditions, parA antisense expression in M. smegmatis resulted in reduced growth. This effect on growth provided a basis for the detection of compounds that increased susceptibility to expression of parA antisense. Two compounds identified from library screening, phenoxybenzamine and octoclothepin, also inhibited the in vitro ATPase activity of ParA from M. tuberculosis. Structural in silico analyses predict that phenoxybenzamine and octoclothepin undergo interactions compatible with the active site of ParA. Octoclothepin exhibited significant bacteriostatic activity towards M. tuberculosis.
conclusionsOur data support the use of whole-cell differential antisense screens for the discovery of inhibitors of specific anti-tubercular drug targets. Using this approach, we have identified an inhibitor of purified ParA and whole cells of M. tuberculosis.
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