title: Discovery of anti-TB agents that target the cell-division protein FtsZ.
abstract: The emergence of multidrug-resistant Mycobacterium tuberculosis strains has made many of the currently available anti-tuberculosis (TB) drugs ineffective. Accordingly, there is a pressing need to identify new drug targets. Filamentous temperature-sensitive protein Z (FtsZ), a bacterial tubulin homologue, is an essential cell-division protein that polymerizes in a GTP-dependent manner, forming a highly dynamic cytokinetic ring, designated as the Z ring, at the septum site. Other cell-division proteins are recruited to the Z ring and, upon resolution of the septum, two daughter cells are produced. Since inactivation of FtsZ or alteration of FtsZ assembly results in the inhibition of Z-ring and septum formation, FtsZ is a very promising target for novel antimicrobial drug development. This review describes the function and dynamic behaviors of FtsZ and the recent development of FtsZ inhibitors as potential anti-TB agents.
authors.affiliation: Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA.
authors.forename: Kunal
authors.initials: K
authors.lastname: Kumar
authors.forename: Divya
authors.initials: D
authors.lastname: Awasthi
authors.forename: William T
authors.initials: WT
authors.lastname: Berger
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Tonge
authors.forename: Richard A
authors.initials: RA
authors.lastname: Slayden
authors.forename: Iwao
authors.initials: I
authors.lastname: Ojima
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria