ArticlePloS one2009
Delineating bacteriostatic and bactericidal targets in mycobacteria using IPTG inducible antisense expression.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 64 citations in OpenAlex.
- An integrated complete-genome sequencing and systems biology approach to predict antimicrobial resistance genes in the virulent bacterial strains of Moraxella catarrhalis.Briefings in functional genomics · 2026Article
- Vacuolar-ATPase inhibitors are antimicrobial agents active against intracellular mycobacteria.Antimicrobial agents and chemotherapy · 2025Article
- The evolution of heteroresistance via small colony variants in Escherichia coli following long term exposure to bacteriostatic antibiotics.Nature communications · 2024Article
- The Evolution of Heteroresistance via Small Colony Variants inbioRxiv : the preprint server for biology · 2024Article
- An integrated complete-genome sequencing and systems biology approach to predict antimicrobial resistance genes in the virulent bacterial strains of Moraxella catarrhalis.Briefings in functional genomics · 2023Article
- Mycobacterial Genetic Technologies for Probing the Host-Pathogen Microenvironment.Infection and immunity · 2023Review
- Potentiating the Anti-Tuberculosis Efficacy of Peptide Nucleic Acids through Combinations with Permeabilizing Drugs.Microbiology spectrum · 2022Article
- Impact of Target Turnover on the Translation of Drug-Target Residence Time to Time-Dependent Antibacterial Activity.ACS infectious diseases · 2021Article
- Identification of Mutations Conferring Tryptanthrin Resistance toAntibiotics (Basel, Switzerland) · 2020Article
- Correlating Drug-Target Residence Time and Post-antibiotic Effect: Insight into Target Vulnerability.ACS infectious diseases · 2020Article
- RepTB: a gene ontology based drug repurposing approach for tuberculosis.Journal of cheminformatics · 2018Article
- Drug-Target Kinetics in Drug Discovery.ACS chemical neuroscience · 2018Article
- Ser/Thr Phosphorylation Regulates the Fatty Acyl-AMP Ligase Activity of FadD32, an Essential Enzyme in Mycolic Acid Biosynthesis.The Journal of biological chemistry · 2016Article
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- Benzoic Acid-Inducible Gene Expression in Mycobacteria.PloS one · 2015Article
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- Article
- Assessment of Mycobacterium tuberculosis pantothenate kinase vulnerability through target knockdown and mechanistically diverse inhibitors.Antimicrobial agents and chemotherapy · 2014Article
- Bacterial cellular engineering by genome editing and gene silencing.International journal of molecular sciences · 2014Review
- Regulated Expression Systems for Mycobacteria and Their Applications.Microbiology spectrum · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In order to identify novel high value antibacterial targets it is desirable to delineate whether the inactivation of the target enzyme will lead to bacterial death or stasis. This knowledge is particularly important in slow growing organisms, like mycobacteria, where most of the viable anti-tubercular agents are bactericidal. A bactericidal target can be identified through the conditional deletion or inactivation of the target gene at a relatively high cell number and subsequently following the time course of survival for the bacteria. A simple protocol to execute conditional inactivation of a gene is by antisense expression. We have developed a mycobacteria specific IPTG inducible vector system and monitored the effect of antisense inhibition of several known essential genes in mycobacteria by following their survival kinetics. By this method, we could differentiate between genes whose down regulation lead to bacteriostatic or bactericidal effect. Targets for standard anti-tubercular drugs like inhA for isoniazid, rpoB and C for rifampicin, and gyr A/B for flouroquinolones were shown to be bactericidal. In contrast targets like FtsZ behaved in a bacteriostatic manner. Induction of antisense expression in embB and ribosomal RNA genes, viz., rplJ and rpsL showed only a marginal growth inhibition. The specificity of the antisense inhibition was conclusively shown in the case of auxotrophic gene ilvB. The bactericidal activity following antisense expression of ilvB was completely reversed when the growth media was supplemented with the isoleucine, leucine, valine and pantothenate. Additionally, under these conditions the expression of several genes in branched chain amino acid pathway was severely suppressed indicating targeted gene inactivation.
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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.