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

1)通过气管内接种铜绿假单胞菌抽动运动野生株和突变株，建立小鼠慢性呼吸道感染模型，探讨抽动运动的发病机制。结果表明，抽动运动通过将宿主防御从Th1转移到Th1而与慢性呼吸道感染的发生密切相关。2)在该模型中，给予大环内酯类抗生素12周，通过诱导干扰素-γ产生Th1免疫反应来提高小鼠的存活率，与突变株模型中的方式平行。此外，体外实验还证实了14元和15元环大环内酯类化合物对铜绿假单胞菌抽动运动的抑制作用。提示抑制抽动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机制之一。3)此外，卡半胱素治疗12周还能抑制小鼠气管内插入塑料管的铜绿假单胞菌生物被膜的形成。该药能显著抑制细菌在体外的生物被膜形成。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。

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.