title: Waldiomycin, a novel WalK-histidine kinase inhibitor from Streptomyces sp. MK844-mF10.
abstract: WalK, a histidine kinase, and WalR, a response regulator, make up a two-component signal transduction system that is indispensable for the cell-wall metabolism of low GC Gram-positive bacteria. WalK inhibitors are likely to show bactericidal effects against methicillin-resistant Staphylococcus aureus . We discovered a new WalK inhibitor, designated waldiomycin, by screening metabolites from actinomycetes. Waldiomycin belongs to the family of angucycline antibiotics and is structurally related to dioxamycin. Waldiomycin inhibits WalK from S. aureus and Bacillus subtilis at IC50s 8.8 and 10.2 μM, respectively, and shows antibacterial activity with MICs ranging from 4 to 8 μg ml(-1) against methicillin-resistant S. aureus and B. subtilis.
authors: Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan. igarashim@bikaken.or.jp
authors: Masayuki
authors: M
authors: Igarashi
authors: Takafumi
authors: T
authors: Watanabe
authors: Tomohiro
authors: T
authors: Hashida
authors: Maya
authors: M
authors: Umekita
authors: Masaki
authors: M
authors: Hatano
authors: Yohei
authors: Y
authors: Yanagida
authors: Hirokazu
authors: H
authors: Kino
authors: Tomoyuki
authors: T
authors: Kimura
authors: Naoko
authors: N
authors: Kinoshita
authors: Kunio
authors: K
authors: Inoue
authors: Ryuichi
authors: R
authors: Sawa
authors: Yoshio
authors: Y
authors: Nishimura
authors: Ryutaro
authors: R
authors: Utsumi
authors: Akio
authors: A
authors: Nomoto
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects*; D000071677:Histidine Kinase; D020128:Inhibitory Concentration 50; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D011809:Quinones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013302:Streptomyces / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D047428:Protein Kinase Inhibitors; D011809:Quinones; C584027:waldiomycin; D011494:Protein Kinases; D000071677:Histidine Kinase