The prokaryotic cytoskeleton: a putative target for inhibitors and antibiotics?
In the recent decade, our view on the organization of the bacterial cell has been revolutionized by the identification of cytoskeletal elements. Most bacterial species have structural homologs of actin and tubulin that assemble into dynamic, filamentous structures at precisely defined sub-cellular locations. The essential cell division protein FtsZ forms a dynamic ring at mid-cell and is similar in its structure to tubulin. Proteins of the MreB family, which are structural homologs of actin, assemble into helical or straight filaments in the bacterial cytoplasm. As in eukaryotic cells, the bacterial cytoskeleton drives essential cellular processes such as cell division, cell wall growth, DNA movement, protein targeting, and alignment of organelles. Different high-throughput assays have been developed to search for inhibitors of components of the bacterial cytoskeleton. Cell-based assays for the detection of cell division inhibitors as well as FtsZ GTPase assays led to the identification of several compounds that inhibit the polymerization of FtsZ, by this blocking bacterial cell division. Such inhibitors might not only be valuable tools for basic research, but might also lead to novel therapeutic agents against pathogenic bacteria. For example, the polyphenol dichamanetin, the 2-alkoxycarbonylaminopyridine SRI-3072, and the benzophenanthridine alkaloid sanguinarine inhibit the GTPase activity of FtsZ and exhibit antimicrobial activity.
Vollmer
Waldemar
W
Mikrobielle Genetik, Universität Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany. waldemar.vollmer@uni-tuebingen.de
D000470:Alkaloids / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000502:physiology; D053119:Benzophenanthridines / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects* / Q000502:physiology*; D044950:Flavanones / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D011621:Pteridines / Q000494:pharmacology
D000470:Alkaloids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D053119:Benzophenanthridines; D002219:Carbamates; D003598:Cytoskeletal Proteins; D044950:Flavanones; C071525:FtsZ protein, Bacteria; D007546:Isoquinolines; D011621:Pteridines; C512547:dichamanetin; C471411:ethyl (8-((4-(diethylamino)-1-methylbutyl)amino)-2,3-diphenylpyrido(2,3-b)pyrazin-6-yl)carbamate; C005705:sanguinarine