Adebali Ogun, Petukh Marharyta G, Reznik Alexander O, Tishkov Artem V, Upadhyay Amit A, Zhulin Igor B
Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA.
Computational Sciences and Engineering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA.
J Bacteriol. 2017 Aug 22;199(18). doi: 10.1128/JB.00218-17. Print 2017 Sep 15.
Histidine kinases are key components of regulatory systems that enable bacteria to respond to environmental changes. Two major classes of histidine kinases are recognized on the basis of their modular design: classical (HKI) and chemotaxis specific (HKII). Recently, a new type of histidine kinase that appeared to have features of both HKIs and HKIIs was identified and termed HKIII; however, the details of HKIII's relationship to other two classes of histidine kinases, their function, and evolutionary history remain unknown. Here, we carried out genomic, phylogenetic, and protein sequence analyses that allowed us to reveal the unusual evolutionary history of this protein family, formalize its distinctive features, and propose its putative function. HKIIIs are characterized by the presence of sensory domains and the lack of a dimerization domain, which is typically present in all histidine kinases. In addition to a single-domain response regulator, HKIII signal transduction systems utilize CheX phosphatase and, in many instances, an unorthodox soluble chemoreceptor that are usual components of chemotaxis signal transduction systems. However, many HKIII genes are found in genomes completely lacking chemotaxis genes, thus decoupling their function from chemotaxis. By contrast, all HKIII-containing genomes also contain , a marker gene for bacterial type IV pilus-based motility, whose regulation is proposed as a putative function for HKIII. These signal transduction systems have a narrow phyletic distribution but are present in many emerging and opportunistic pathogens, thus offering an attractive potential target for future antimicrobial drug design. Bacteria adapt to their environment and their hosts by detecting signals and regulating their cellular functions accordingly. Here, we describe a largely unexplored family of signal transduction histidine kinases, called HKIII, that have a unique modular design. While they are currently identified in a relatively short list of bacterial species, this list contains many emerging pathogens. We show that HKIIIs likely control bacterial motility across solid surfaces, which is a key virulence factor in many bacteria, including those causing severe infections. Full understanding of this putative function may help in designing effective drugs against pathogens that will not affect the majority of the beneficial human microbiome.
组氨酸激酶是调控系统的关键组成部分，使细菌能够对环境变化做出反应。根据其模块设计可识别出两类主要的组氨酸激酶：经典型（HKI）和趋化特异性型（HKII）。最近，一种似乎兼具HKI和HKII特征的新型组氨酸激酶被鉴定出来并命名为HKIII；然而，HKIII与其他两类组氨酸激酶的关系细节、其功能以及进化历史仍不清楚。在此，我们进行了基因组、系统发育和蛋白质序列分析，从而揭示了这个蛋白质家族不同寻常的进化历史，明确了其独特特征，并提出了其假定功能。HKIII的特点是存在传感结构域且缺乏通常在所有组氨酸激酶中都存在的二聚化结构域。除了单结构域应答调节蛋白外，HKIII信号转导系统还利用CheX磷酸酶，并且在许多情况下利用一种非传统的可溶性化学感受器，这些都是趋化信号转导系统的常见组成部分。然而，许多HKIII基因存在于完全缺乏趋化基因的基因组中，因此使其功能与趋化作用脱钩。相比之下，所有含有HKIII的基因组也都含有 ，这是基于细菌IV型菌毛运动的一个标记基因，其调控被认为是HKIII的一种假定功能。这些信号转导系统的系统发育分布狭窄，但存在于许多新兴和机会性病原体中，因此为未来的抗菌药物设计提供了一个有吸引力的潜在靶点。细菌通过检测信号并相应地调节其细胞功能来适应其环境和宿主。在此，我们描述了一个很大程度上未被探索的信号转导组氨酸激酶家族，称为HKIII，其具有独特的模块设计。虽然目前仅在相对较少的细菌物种中鉴定出它们，但这个列表中包含许多新兴病原体。我们表明，HKIII可能控制细菌在固体表面的运动，这是许多细菌（包括那些引起严重感染的细菌）的关键毒力因子。对这种假定功能的全面了解可能有助于设计针对病原体的有效药物，而不会影响大多数有益的人类微生物群。
