Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa

Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa
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DOI:
10.1073/pnas.1502025112
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发表时间:
2015-06-16
影响因子:
11.1
通讯作者:
Gitai, Zemer
Gitai, Zemer
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Persat, Alexandre;Inclan, Yuki F.;Gitai, Zemer

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细菌已经进化出广泛的传感系统,以适当地响应环境信号。在这里,我们证明了机会致病菌铜绿假单胞菌检测接触表面的短时间尺度上使用其IV型皮利,一个主要的表面粘附的机械活动。这种信号转导机制需要IV型皮利附着于固体表面,然后通过Chp化学感受系统进行菌毛收缩和信号转导,Chp化学感受系统是一种趋化性样感觉系统,调节cAMP产生和数百个基因(包括关键毒力因子)的转录。与其他趋化性途径一样,菌毛介导的表面感应导致通过增加IV型皮利活性的正反馈放大的瞬时应答,从而促进可刺激额外毒力和生物膜诱导途径的长期表面附着。甲基接受趋化蛋白样化学传感器PilJ直接与主要的菌毛蛋白亚基PilA相互作用。因此,我们的研究结果支持一个机械化学模型,其中化学传感系统测量拉伸IV型皮利的机械诱导的构象变化。这些发现表明,铜绿假单胞菌不仅使用IV型皮利进行表面特异性抽搐运动,而且还作为调节表面诱导的基因表达和致病性的传感器。
Bacteria have evolved a wide range of sensing systems to appropriately respond to environmental signals. Here we demonstrate that the opportunistic pathogen Pseudomonas aeruginosa detects contact with surfaces on short timescales using the mechanical activity of its type IV pili, a major surface adhesin. This signal transduction mechanism requires attachment of type IV pili to a solid surface, followed by pilus retraction and signal transduction through the Chp chemosensory system, a chemotaxis-like sensory system that regulates cAMP production and transcription of hundreds of genes, including key virulence factors. Like other chemotaxis pathways, pili-mediated surface sensing results in a transient response amplified by a positive feedback that increases type IV pili activity, thereby promoting long-term surface attachment that can stimulate additional virulence and biofilm-inducing pathways. The methyl-accepting chemotaxis protein-like chemosensor PilJ directly interacts with the major pilin subunit PilA. Our results thus support a mechanochemical model where a chemosensory system measures the mechanically induced conformational changes in stretched type IV pili. These findings demonstrate that P. aeruginosa not only uses type IV pili for surface-specific twitching motility, but also as a sensor regulating surface-induced gene expression and pathogenicity.