Transcriptional Regulatory Systems in Pseudomonas: A Comparative Analysis of Helix-Turn-Helix Domains and Two-Component Signal Transduction Networks.

Abdelali Daddaoua, Zulema Udaondo, Kelsey Aguirre Schilder, Ana Rosa Márquez Blesa, Mireia Tena-Garitaonaindia, José Canto Mangana

Journal: International journal of molecular sciences 2025;26(10):

PMID: 40429820

Abstract

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.

Address: 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.; Department of Biochemistry and Molecular Biology II, Pharmacy School, University of Granada, 18071 Granada, Spain.; Pharmacy Services, A.S. Hospital de Poniente de Almería, 04700 El Ejido, Spain.; Department of Biochemistry and Molecular Biology II, Pharmacy School, University of Granada, 18071 Granada, Spain.; Biosanitary Research Institute of Granada (IBS), 18014 Granada, Spain.; Institute of Nutrition and Food Technology "José Mataix", Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. Armilla, 18016 Granada, Spain.
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