Anti-infectious effect of S-benzylisothiourea compound A22, which inhibits the actin-like protein, MreB, in Shigella flexneri.
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.
Noguchi
Norihisa
N
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan. noguchin@ps.toyaku.ac.jp
Yanagimoto
Keita
K
Nakaminami
Hidemasa
H
Wakabayashi
Moeru
M
Iwai
Noritaka
N
Wachi
Masaaki
M
Sasatsu
Masanori
M
D000199:Actins / Q000737:chemistry; D000818:Animals; D000890:Anti-Infective Agents; D001419:Bacteria / Q000187:drug effects; D001421:Bacteria, Anaerobic / Q000187:drug effects / Q000648:ultrastructure; D016466:CHO Cells; D002448:Cell Adhesion; D006224:Cricetinae; D003412:Cricetulus; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests; D012763:Shigella flexneri / Q000187:drug effects* / Q000472:pathogenicity / Q000648:ultrastructure; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D000199:Actins; D000890:Anti-Infective Agents; D003598:Cytoskeletal Proteins; C015799:2,6-dichlorobenzylthiopseudourea; D013890:Thiourea