RRC ID 43407
著者 Noguchi N, Yanagimoto K, Nakaminami H, Wakabayashi M, Iwai N, Wachi M, Sasatsu M.
タイトル Anti-infectious effect of S-benzylisothiourea compound A22, which inhibits the actin-like protein, MreB, in Shigella flexneri.
ジャーナル Biol Pharm Bull
Abstract S-Benzylisothiourea compound A22 induces coccoid forms in Escherichia coli by inhibiting the function of the actin-like cytoskeletal protein, MreB. The minimum inhibitory concentration of A22 and the minimum concentration to induce coccoid forms for various pathogenic bacteria were determined. At 10 microg/ml, A22 induced coccoid forms in Shigella flexneri but did not inhibit the growth. No alteration of coccoid forms in the Gram-positive bacteria and anaerobic bacteria tested were observed following treatment with A22. To study the relationship between pathogenicity and alterations in bacterial shape, the infectious capacity of A22-induced coccoid S. flexneri was examined using CHO-K1 cells. Invasion of the coccoid cells was significantly reduced, however, no changes in adherence were observed. Using a mutant defective in the type III secretion apparatus, which delivers effectors to the host, we examined the secretion of effectors by A22-induced coccoid S. flexneri. The amount of secreted effectors in the coccoid cells was clearly decreased compared to rod-shaped cells. These results showed that the maintenance of rod-shaped cells by MreB in bacteria was essential for the secretion of effectors via the type III secretion system. Therefore, our results suggest that A22 is a useful lead compound for a novel anti-infectious agent without bactericidal activity and MreB is a candidate target site for development of new anti-infectious agents.
巻・号 31(7)
ページ 1327-32
公開日 2008-7-1
DOI 10.1248/bpb.31.1327
PII JST.JSTAGE/bpb/31.1327
PMID 18591769
MeSH Actins / chemistry Animals Anti-Infective Agents* Bacteria / drug effects Bacteria, Anaerobic / drug effects Bacteria, Anaerobic / ultrastructure CHO Cells Cell Adhesion Cricetinae Cricetulus Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism* Electrophoresis, Polyacrylamide Gel Gram-Positive Bacteria / drug effects Gram-Positive Bacteria / ultrastructure Microbial Sensitivity Tests Shigella flexneri / drug effects* Shigella flexneri / pathogenicity Shigella flexneri / ultrastructure Thiourea / analogs & derivatives* Thiourea / pharmacology
IF 1.863
引用数 14
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞