Udaondo Zulema, Schilder Kelsey Aguirre, Blesa Ana Rosa Márquez, Tena-Garitaonaindia Mireia, Mangana José Canto, Daddaoua Abdelali
Department of Environmental Protection, Consejo Superior de Investigaciones Científicas, Estación Experimental del Zaidin, 18008 Granada, Spain.
Department of Biochemistry and Molecular Biology II, Pharmacy School, University of Granada, 18071 Granada, Spain.
Int J Mol Sci. 2025 May 14;26(10):4677. doi: 10.3390/ijms26104677.
Bacterial communities in diverse environmental niches respond to various external stimuli for survival. A primary means of communication between bacterial cells involves one-component (OC) and two-component signal transduction systems (TCSs). These systems are key for sensing environmental changes and regulating bacterial physiology. TCSs, which are the more complex of the two, consist of a sensor histidine kinase for receiving an external input and a response regulator to convey changes in bacterial cell physiology. For numerous reasons, TCSs have emerged as significant targets for antibacterial drug design due to their role in regulating expression level, bacterial viability, growth, and virulence. Diverse studies have shown the molecular mechanisms by which TCSs regulate virulence and antibiotic resistance in pathogenic bacteria. In this study, we performed a thorough analysis of the data from multiple public databases to assemble a comprehensive catalog of the principal detection systems present in both the non-pathogenic KT2440 and the pathogenic PAO1 strains. Additionally, we conducted a sequence analysis of regulatory elements associated with transcriptional proteins. These were classified into regulatory families based on Helix-turn-Helix (HTH) protein domain information, a common structural motif for DNA-binding proteins. Moreover, we highlight the function of bacterial TCSs and their involvement in functions essential for bacterial survival and virulence. This comparison aims to identify novel targets that can be exploited for the development of advanced biotherapeutic strategies, potentially leading to new treatments for bacterial infections.
不同环境生态位中的细菌群落会对各种外部刺激做出反应以求得生存。细菌细胞之间的一种主要通讯方式涉及单组分(OC)和双组分信号转导系统(TCSs)。这些系统是感知环境变化和调节细菌生理功能的关键。TCSs是两者中更为复杂的系统,由一个用于接收外部输入的传感组氨酸激酶和一个传达细菌细胞生理变化的响应调节因子组成。由于TCSs在调节表达水平、细菌活力、生长和毒力方面的作用,出于多种原因,它们已成为抗菌药物设计的重要靶点。各种研究已经揭示了TCSs调节病原菌毒力和抗生素抗性的分子机制。在本研究中,我们对来自多个公共数据库的数据进行了全面分析,以汇编出非致病性KT2440菌株和致病性PAO1菌株中主要检测系统的综合目录。此外,我们对与转录蛋白相关的调控元件进行了序列分析。这些元件根据螺旋-转角-螺旋(HTH)蛋白结构域信息被分类到不同的调控家族中,HTH是DNA结合蛋白的一种常见结构基序。此外,我们强调了细菌TCSs的功能及其在细菌生存和毒力所必需的功能中的作用。这种比较旨在识别可用于开发先进生物治疗策略的新靶点,有望为细菌感染带来新的治疗方法。