Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Appl Environ Microbiol. 2021 May 11;87(11). doi: 10.1128/AEM.03089-20.
is an opportunistic pathogen that can cause problematic infections at different sites throughout the human body. encodes a large suite of over 60 two-component signaling systems that enable cells to rapidly sense and respond to external signals. Previous work has shown that some of these sensory systems contribute to pathogenesis, but the virulence-associated processes and phenotypic traits that each of these systems controls are still largely unclear. To aid investigations of these sensory systems, we have generated deletion strains for each of 64 genes encoding histidine kinases and one histidine phosphotransferase in PA14. We carried out initial phenotypic characterizations of this collection by assaying these mutants for over a dozen virulence-associated traits, and we found that each of these phenotypes is regulated by multiple sensory systems. Our work highlights the usefulness of this collection for further studies of two-component signaling systems and provides insight into how these systems may contribute to infection. can grow and survive under a wide range of conditions, including as a human pathogen. As such, must be able to sense and respond to diverse signals and cues in its environment. This sensory capability is endowed in part by the hundreds of two-component signaling proteins encoded in the genome, but the precise roles of each remain poorly defined. To facilitate systematic study of the signaling repertoire of PA14, we generated a library of deletion strains, each lacking one of the 64 histidine kinases. By subjecting these strains to a battery of phenotypic assays, we confirmed the functions of many and unveiled roles for dozens of previously uncharacterized histidine kinases in controlling various traits, many of which are associated with virulence. Thus, this work provides new insight into the functions of two-component signaling proteins and provides a resource for future investigations.
是一种机会性病原体,可以在人体的不同部位引起有问题的感染。 编码一大套超过 60 个双组分信号系统,使细胞能够快速感知和响应外部信号。以前的工作表明,其中一些感觉系统有助于 发病机制,但每个系统控制的与毒力相关的过程和表型特征在很大程度上仍不清楚。为了帮助研究这些感觉系统,我们在 PA14 中生成了 64 个编码组氨酸激酶和一个组氨酸磷酸转移酶的基因的缺失菌株。我们通过测定这些突变体的十多个与毒力相关的特征来对这个集合进行初步的表型特征描述,我们发现这些表型中的每一个都受到多个感觉系统的调节。我们的工作突出了这个集合对于进一步研究双组分信号系统的有用性,并提供了对这些系统如何可能有助于 感染的深入了解。 可以在广泛的条件下生长和存活,包括作为人类病原体。因此, 必须能够感知和响应其环境中的各种信号和线索。这种感应能力部分归因于 基因组中编码的数百种双组分信号蛋白,但每个的精确作用仍未明确定义。为了便于系统研究 PA14 的信号转导组,我们生成了一个缺失菌株库,每个菌株都缺失一个组氨酸激酶。通过对这些菌株进行一系列表型测定,我们证实了许多的功能,并揭示了数十个以前未表征的组氨酸激酶在控制各种特征中的作用,其中许多与 毒力有关。因此,这项工作为双组分信号蛋白的功能提供了新的见解,并为未来的研究提供了资源。