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Analysis of twitching motility as a new regulatory mechanism in chronic respiratory infection caused by Pseudomonas aeruginosa

抽搐运动作为铜绿假单胞菌引起的慢性呼吸道感染新调节机制的分析

基本信息

批准号：
16590756
负责人：
KADOTA Jun-ichi
金额：
$ 2.05万
依托单位：
Oita University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

1)To investigate the pathogenesis of twitching motility, a murine model of chronic respiratory infection was established by intratracheal inoculation of wild or mutant strain of twitching motility of P.aeruginosa. The results indicate that twitching motility deeply related to the development of chronic respiratory infection through shifting the host defence from Th1 to Th2.2)In this model infected with wild strain, 12-week administration of macrolide antibiotic increased mice survival by inducing IFN-γ producing Th1 immune response in parallel with the manner seen in th model with mutant strain. Furthermore, in vitro study demonstrated the inhibition of P.aeruginosa twitching motility by 14- and 15-membered ring macrolides. This suggest that the suppression of twitching motility is one of the mechanism by which macrolide antibiotics have a therapeutic effect on chronic P.aeruginosa respiratory infection.3)In addition, 12-week carbocystein treatment also inhibited biofilm formation of P.aeruginosa on plastic tube inserted into trachea of mice. The drug significantly inhibited in vitro biofilm formation of the bacteria. This result may provide another therapeutic strategy for chronic P.aeruginosa respiratory infection.

1）为探讨颤搐运动的发病机制，采用气管内接种铜绿假单胞菌颤搐运动野生株和突变株，建立慢性呼吸道感染小鼠模型。结果表明，抽搐运动通过将宿主防御从Th 1转移到Th 2而与慢性呼吸道感染的发展密切相关。2）在用野生型菌株感染的该模型中，大环内酯类抗生素给药12周通过诱导产生IFN-γ的Th 1免疫应答而增加小鼠的存活率，与用突变型菌株感染的模型中观察到的方式平行。此外，体外研究表明，14-和15-元环大环内酯类药物抑制铜绿假单胞菌的抽搐运动。提示抑制颤搐运动是大环内酯类抗生素治疗慢性铜绿假单胞菌呼吸道感染的作用机制之一。3）另外，12周的碳半胱氨酸治疗也能抑制铜绿假单胞菌在气管插管上的生物被膜形成。该药物显著抑制细菌的体外生物膜形成。这一结果可能为慢性铜绿假单胞菌呼吸道感染提供另一种治疗策略。

项目成果

期刊论文数量（30）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Influence of carbocystein (S-CMC) on biofilm formation of Pseudomonas aeruginosa

碳半胱氨酸（S-CMC）对铜绿假单胞菌生物膜形成的影响

DOI：
发表时间：
2004
期刊：
Bacterial Adherence & Biofilm 18
影响因子：
0
作者：
Kishi K;et al.
通讯作者：
et al.

Effect of Erythromycin on Chronic Respiratory Infection Caused by Pseudomonas aeruginosa with Biofilm Formation in an Experimental Murine Model

DOI：
10.1128/aac.48.6.2251-2259.2004
发表时间：
2004-06
期刊：
Antimicrobial Agents and Chemotherapy
影响因子：
4.9
作者：
T. Nagata;H. Mukae;J. Kadota;Tomayoshi Hayashi;T. Fujii;M. Kuroki;R. Shirai;K. Yanagihara;K. Tomono;T. Koji;S. Kohno
通讯作者：
T. Nagata;H. Mukae;J. Kadota;Tomayoshi Hayashi;T. Fujii;M. Kuroki;R. Shirai;K. Yanagihara;K. Tomono;T. Koji;S. Kohno

Role of Pseudomonas aeruginosa quorum-sensing systems in a mouse model of chronic respiratory infection