Anti-infectious Effect of S-Benzylisothiourea Compound A22, Which Inhibits the Actin-Like Protein, MreB, in Shigella flexneri(Microbiology)
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概要
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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 μg/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 antiinfectious agent without bactericidal activity and MreB is a candidate target site for development of new anti-infectious agents.
- 公益社団法人日本薬学会の論文
- 2008-07-01
著者
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Wachi Masaaki
Department of Bioengineering, Tokyo Institute of Technology
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NOGUCHI Norihisa
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science
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NAKAMINAMI Hidemasa
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science
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SASATSU Masanori
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science
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Noguchi Norihisa
Department Of Microbiology School Of Pharmacy Tokyo University Of Pharmacy And Life Sciences
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Noguchi Norihisa
Department Of Microbiology School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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Noguchi Norihisa
Tokyo University Of Pharmacy And Life Science
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Wachi Masaaki
Department Of Bioengineering Graduate School Of Bioscience And Biotechnology Tokyo Institute Of Tech
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Sasatsu Masanori
Department Of Microbiology School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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YANAGIMOTO Keita
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science
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WAKABAYASHI Moeru
Department of Microbiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science
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IWAI Noritaka
Department of Bioengineering, Tokyo Institute of Technology
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Iwai Noritaka
Department Of Bioengineering Tokyo Institute Of Technology
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Yanagimoto Keita
Department Of Microbiology School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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Nakaminami Hidemasa
Department Of Microbiology School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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Wakabayashi Moeru
Department Of Microbiology School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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