ArticleBiochemistry2009
A22 disrupts the bacterial actin cytoskeleton by directly binding and inducing a low-affinity state in MreB.
Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 172 citations in OpenAlex.
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- Control Targets in Plant-Pathogenic Bacteria: From Growth-Essential Processes to Anti-Virulence Strategies and Candidate Targets inPlants (Basel, Switzerland) · 2026Review
- Direct interaction between MreB and the RodA-PBP2 complex organizes lateral cell wall synthesis inmLife · 2026Article
- Bacterial actin MreB as a new antibiotic target.Frontiers in molecular biosciences · 2026Article
- Distinct modes of cell division drivemBio · 2025Article
- Advances in Small Molecule Inhibitors Targeting the Bacterial Lipoprotein Transport System (Lol) in Gram-Negative Bacteria.Chemistry, an Asian journal · 2025Review
- MreB: unraveling the molecular mechanisms of bacterial shape, division, and environmental adaptation.Cell communication and signaling : CCS · 2025Review
- Nonequilibrium polysome dynamics promote chromosome segregation and its coupling to cell growth ineLife · 2025Article
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- Age-Dependent Pleomorphism inMicroorganisms · 2025Article
- Cell shape affects bacterial colony growth under physical confinement.Nature communications · 2024Article
- Deciphering the impact of MreB on the morphology and pathogenicity of the aquatic pathogen Spiroplasma eriocheiris.Biology direct · 2024Article
- Wiring Between Close Nodes in Molecular Networks Evolves More Quickly Than Between Distant Nodes.Molecular biology and evolution · 2024Article
- MinD-RNase E interplay controls localization of polar mRNAs in E. coli.The EMBO journal · 2024Article
- Relationship between the Rod complex and peptidoglycan structure in Escherichia coli.MicrobiologyOpen · 2023Article
- The role of CenKR in the coordination ofmBio · 2023Article
- A conserved zinc-binding site inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Solubility and Thermal Stability ofInternational journal of molecular sciences · 2022Article
- Omnipose: a high-precision morphology-independent solution for bacterial cell segmentation.Nature methods · 2022Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
S-(3,4-Dichlorobenzyl)isothiourea (A22) disrupts the actin cytoskeleton of bacteria, causing defects of morphology and chromosome segregation. Previous studies have suggested that the actin homologue MreB itself is the target of A22, but there has been no direct observation of A22 binding to MreB and no mechanistic explanation of its mode of action. We show that A22 binds MreB with at least micromolar affinity in its nucleotide-binding pocket in a manner that is sterically incompatible with simultaneous ATP binding. A22 negatively affects both the time course and extent of MreB polymerization in vitro in the presence of ATP. A22 prevents assembly of MreB into long, rigid polymers, as determined by both fluorescence microscopy and sedimentation assays. A22 increases the critical concentration of ATP-bound MreB assembly from 500 nM to approximately 2000 nM. We therefore conclude that A22 is a competitive inhibitor of ATP binding to MreB. A22-bound MreB is capable of polymerization, but with assembly properties that more closely resemble those of the ADP-bound state. Because the cellular concentration of MreB is in the low micromolar range, this mechanism explains the ability of A22 to largely disassemble the actin cytoskeleton in bacterial cells. It also represents a novel mode of action for a cytoskeletal drug and the first biochemical characterization of the interaction between a small molecule inhibitor of the bacterial cytoskeleton and its target.
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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.