ArticlePLoS pathogens2009
Targeting the replication initiator of the second Vibrio chromosome: towards generation of vibrionaceae-specific antimicrobial agents.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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
12 citing papers in PubMed, 25 citations in OpenAlex.
- Blocking the Trigger: Inhibition of the Initiation of Bacterial Chromosome Replication as an Antimicrobial Strategy.Antibiotics (Basel, Switzerland) · 2019Review
- In Silico Screening and Analysis of Broad-Spectrum Molecular Targets and Lead Compounds for Diarrhea Therapy.Bioinformatics and biology insights · 2019Article
- Establishing a System for Testing Replication Inhibition of the Vibrio cholerae Secondary Chromosome in Escherichia coli.Antibiotics (Basel, Switzerland) · 2017Article
- DNA replication proteins as potential targets for antimicrobials in drug-resistant bacterial pathogens.The Journal of antimicrobial chemotherapy · 2017Review
- The replication initiator of the cholera pathogen's second chromosome shows structural similarity to plasmid initiators.Nucleic acids research · 2017Article
- In vitro and in vivo activities of HPi1, a selective antimicrobial against Helicobacter pylori.Antimicrobial agents and chemotherapy · 2014Article
- Initiator protein dimerization plays a key role in replication control of Vibrio cholerae chromosome 2.Nucleic acids research · 2014Article
- Chromosome dynamics in multichromosome bacteria.Biochimica et biophysica acta · 2012Review
- Architecture and conservation of the bacterial DNA replication machinery, an underexploited drug target.Current drug targets · 2012Review
- Genome engineering in Vibrio cholerae: a feasible approach to address biological issues.PLoS genetics · 2012Article
- Regulatory cross-talk links Vibrio cholerae chromosome II replication and segregation.PLoS genetics · 2011Article
- Antimicrobials & cholera: are we stranded?The Indian journal of medical research · 2011Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The Vibrionaceae is comprised of numerous aquatic species and includes several human pathogens, such as Vibrio cholerae, the cause of cholera. All organisms in this family have two chromosomes, and replication of the smaller one depends on rctB, a gene that is restricted to the Vibrionaceae. Given the increasing prevalence of multi-drug resistance in pathogenic vibrios, there is a need for new targets and drugs to combat these pathogens. Here, we carried out a high throughput cell-based screen to find small molecule inhibitors of RctB. We identified a compound that blocked growth of an E. coli strain bearing an rctB-dependent plasmid but did not influence growth of E. coli lacking this plasmid. This compound, designated vibrepin, had potent cidal activity against V. cholerae and inhibited the growth of all vibrio species tested. Vibrepin blocked RctB oriCII unwinding, apparently by promoting formation of large non-functional RctB complexes. Although vibrepin also appears to have targets other than RctB, our findings suggest that RctB is an attractive target for generation of novel antibiotics that only block growth of vibrios. Vibrio-specific agents, unlike antibiotics currently used in clinical practice, will not engender resistance in the normal human flora or in non-vibrio environmental microorganisms.
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Registered trials
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.