ArticleJournal of bacteriology2007
A Novel indole compound that inhibits Pseudomonas aeruginosa growth by targeting MreB is a substrate for MexAB-OprM.
Article in Journal of bacteriology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
27 citing papers in PubMed, 52 citations in OpenAlex.
- Evolutionary rescue of sphericaleLife · 2025Article
- Novel MreB inhibitors with antibacterial activity against Gram (-) bacteria.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2022Article
- TXH11106: A Third-Generation MreB Inhibitor with Enhanced Activity against a Broad Range of Gram-Negative Bacterial Pathogens.Antibiotics (Basel, Switzerland) · 2022Article
- Structure-based inhibitor design for reshaping bacterial morphology.Communications biology · 2022Article
- The Quorum-Sensing Inhibitor Furanone C-30 Rapidly Loses Its Tobramycin-Potentiating Activity against Pseudomonas aeruginosa Biofilms during Experimental Evolution.Antimicrobial agents and chemotherapy · 2021Article
- Synergistic Antibacterial and Antibiofilm Activity of the MreB Inhibitor A22 Hydrochloride in Combination with Conventional Antibiotics againstInternational journal of microbiology · 2021Article
- Bacteriostatic Potential of Melatonin: Therapeutic Standing and Mechanistic Insights.Frontiers in immunology · 2021Review
- The evolution of spherical cell shape; progress and perspective.Biochemical Society transactions · 2019Review
- In vitro studies evaluating the activity of imipenem in combination with relebactam against Pseudomonas aeruginosa.BMC microbiology · 2019Article
- Host metabolites stimulate the bacterial proton motive force to enhance the activity of aminoglycoside antibiotics.PLoS pathogens · 2019Article
- Pathway-Directed Screen for Inhibitors of the Bacterial Cell Elongation Machinery.Antimicrobial agents and chemotherapy · 2019Article
- Status of Targeting MreB for the Development of Antibiotics.Frontiers in chemistry · 2019Review
- Targeting the Bacterial Cytoskeleton of theInternational journal of molecular sciences · 2018Article
- Regulatory protein SrpA controls phage infection and core cellular processes in Pseudomonas aeruginosa.Nature communications · 2018Article
- Article
- Determinants of Bacterial Morphology: From Fundamentals to Possibilities for Antimicrobial Targeting.Frontiers in microbiology · 2017Review
- Mutant Alleles of lptD Increase the Permeability of Pseudomonas aeruginosa and Define Determinants of Intrinsic Resistance to Antibiotics.Antimicrobial agents and chemotherapy · 2016Article
- The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria.Clinical microbiology reviews · 2015Review
- Kibdelomycin is a bactericidal broad-spectrum aerobic antibacterial agent.Antimicrobial agents and chemotherapy · 2015Article
- Revealing bacterial targets of growth inhibitors encoded by bacteriophage T7.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug efflux systems contribute to the intrinsic resistance of Pseudomonas aeruginosa to many antibiotics and biocides and hamper research focused on the discovery and development of new antimicrobial agents targeted against this important opportunistic pathogen. Using a P. aeruginosa PAO1 derivative bearing deletions of opmH, encoding an outer membrane channel for efflux substrates, and four efflux pumps belonging to the resistance nodulation/cell division class including mexAB-oprM, we identified a small-molecule indole-class compound (CBR-4830) that is inhibitory to growth of this efflux-compromised strain. Genetic studies established MexAB-OprM as the principal pump for CBR-4830 and revealed MreB, a prokaryotic actin homolog, as the proximal cellular target of CBR-4830. Additional studies establish MreB as an essential protein in P. aeruginosa, and efflux-compromised strains treated with CBR-4830 transition to coccoid shape, consistent with MreB inhibition or depletion. Resistance genetics further suggest that CBR-4830 interacts with the putative ATP-binding pocket in MreB and demonstrate significant cross-resistance with A22, a structurally unrelated compound that has been shown to promote rapid dispersion of MreB filaments in vivo. Interestingly, however, ATP-dependent polymerization of purified recombinant P. aeruginosa MreB is blocked in vitro in a dose-dependent manner by CBR-4830 but not by A22. Neither compound exhibits significant inhibitory activity against mutant forms of MreB protein that bear mutations identified in CBR-4830-resistant strains. Finally, employing the strains and reagents prepared and characterized during the course of these studies, we have begun to investigate the ability of analogues of CBR-4830 to inhibit the growth of both efflux-proficient and efflux-compromised P. aeruginosa through specific inhibition of MreB function.
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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.