title: Indole prevents Escherichia coli cell division by modulating membrane potential.
abstract: Indole is a bacterial signalling molecule that blocks E. coli cell division at concentrations of 3-5 mM. We have shown that indole is a proton ionophore and that this activity is key to the inhibition of division. By reducing the electrochemical potential across the cytoplasmic membrane of E. coli, indole deactivates MinCD oscillation and prevents formation of the FtsZ ring that is a prerequisite for division. This is the first example of a natural ionophore regulating a key biological process. Our findings have implications for our understanding of membrane biology, bacterial cell cycle control and potentially for the design of antibiotics that target the cell membrane.
authors.affiliation: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, United Kingdom.
authors.forename: Catalin
authors.initials: C
authors.lastname: Chimerel
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Field
authors.forename: Silvia
authors.initials: S
authors.lastname: Piñero-Fernandez
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Keyser
authors.forename: David K
authors.initials: DK
authors.lastname: Summers
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D007211:Indoles / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D008051:Lipid Bilayers / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D021381:Protein Transport / Q000187:drug effects; D061209:Proton Ionophores / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; D029968:Escherichia coli Proteins; C489310:FtsA protein, E coli; C071525:FtsZ protein, Bacteria; D007211:Indoles; D008051:Lipid Bilayers; D008164:Luminescent Proteins; D008565:Membrane Proteins; C462942:MinC protein, E coli; D061209:Proton Ionophores; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; C030374:indole; D000251:Adenosine Triphosphatases; C072069:MinD protein, E coli