title: Multiple effects of benzamide antibiotics on FtsZ function.
abstract: Cell division in almost all bacteria is orchestrated by the essential tubulin homologue FtsZ, which assembles into a ring-like structure and acts as a scaffold for the division machinery. Division was recently validated as an important target for antibiotics by the demonstration that low-molecular-weight inhibitors of FtsZ, called benzamides, can cure mice infected with Staphylococcus aureus. In treated cells of Bacillus subtilis we show that FtsZ assembles into foci throughout the cell, including abnormal locations at the cell poles and over the nucleoid. These foci are not inactive aggregates because they remain dynamic, turning over almost as rapidly as untreated polymers. Remarkably, although division is completely blocked, the foci efficiently recruit division proteins that normally co-assemble with FtsZ. However, they show no affinity for components of the Min or Nucleoid occlusion systems. In vitro, the benzamides strongly promote the polymerization of FtsZ, into hyperstable polymers, which are highly curved. Importantly, even at low concentrations, benzamides transform the structure of the Z ring, resulting in abnormal helical cell division events. We propose that benzamides act principally by promoting an FtsZ protomer conformation that is incompatible with a higher-order level of assembly needed to make a division ring.
authors.affiliation: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Adams
authors.forename: Ling Juan
authors.initials: LJ
authors.lastname: Wu
authors.forename: Lloyd G
authors.initials: LG
authors.lastname: Czaplewski
authors.forename: Jeff
authors.initials: J
authors.lastname: Errington
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001426:Bacterial Proteins / Q000378:metabolism*; D001549:Benzamides / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001549:Benzamides; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria