Bacterial pathogens operate by tightly controlling the pathogenicity to facilitate invasion and survival in host. While small molecule inducers can be designed to modulate pathogenicity to perform studies of pathogen-host interaction, these approaches, due to the diffusion property of chemicals, may have unintended, or pleiotropic effects that can impose limitations on their use. By contrast, light provides superior spatial and temporal resolution. Here, using optogenetics we reengineered GacS of the opportunistic pathogen Pseudomonas aeruginosa, signal transduction protein of the global Gac/Rsm cascade which is of central importance for regulation of infection factors. The resultant protein YGS24 displayed significant light-dependent activity of GacS kinases in Pseudomonas aeruginosa. When introduced in Caenorhabditis elegans host systems, YGS24 stimulated the pathogenicity of PAO1 in BHI and of PA14 in SK medium progressively upon blue-light exposure. This optogenetic system provides an accessible way to spatiotemporally control bacterial pathogenicity in defined host even specific tissues to develop new pathogenesis systems, which may in turn expedite development of innovative therapeutics.

中文翻译：

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工程性Gac / Rsm信号级联，用于铜绿假单胞菌致病性开关的光遗传诱导

细菌病原体通过严格控制其致病性来促进宿主的侵袭和生存。虽然可以设计小分子诱导剂来调节致病性以进行病原体与宿主之间的相互作用的研究，但是由于化学物质的扩散特性，这些方法可能具有意想不到的或多效的作用，可能会限制其使用。相比之下，光提供了出色的空间和时间分辨率。在这里，我们使用光遗传学方法对机会性病原体铜绿假单胞菌的GacS进行了改造，这是全球Gac / Rsm级联的信号转导蛋白，对于调节感染因子至关重要。所得的蛋白质YGS24在铜绿假单胞菌中显示出显着的GacS激酶的光依赖性活性。当在秀丽隐杆线虫宿主系统中引入时，在蓝光照射下，YGS24逐渐刺激BHI中的PAO1和SK培养基中的PA14的致病性。这种光遗传学系统提供了一种可访问的方式，可以在限定的宿主甚至特定组织中时空控制细菌的致病性，以开发新的发病机制，从而可以加快创新疗法的开发。