[Frontiers in Bioscience 17, 1108-1119, January 1, 2012]

Histamine in two component system-mediated bacterial signaling

Dimitrios A. Kyriakidis1, Marina C. Theodorou1, Ekaterini Tiligada2

1Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, Greece,2Department of Pharmacology, Medical School University of Athens, Greece


1. Abstract
2. Introduction
3. Histamine in mammalian cellular physiology
3.1. Histamine metabolism
3.2. Histamine in human physiology and pathophysiology
4. Histamine in bacterial physiology and adaptation
4.1. Bacterial two-component systems
4.1.1. The AtoSC two-component system in E. coli
4.2. Histamine modulation of AtoSC signaling
4.2.1. Histamine involvement in cPHB biosynthesis
4.2.2. Histamine involvement in motility and chemotaxis
5. Histamine in virulence and pathogenicity
6. Conclusions and perspectives
7. Acknowledgments
8. References


Histamine is a key mediator governing vital cellular processes in mammals beyond its decisive role in inflammation. Recent evidence implies additional actions in both eukaryotes and prokaryotes. Besides its function in host defense against bacterial infections, histamine elicits largely undefined actions in microorganisms that may contribute to bacteria-host interactions. Bacterial proliferation and adaptation are governed by sophisticated signal transduction networks, including the versatile two-component systems (TCSs) that comprise sensor histidine kinases and response regulators and rely on phosphotransfer mechanisms to exert their modulatory function. The AtoSC TCS regulates fundamental cellular processes such as short-chain fatty acid metabolism, poly-(R)-3-hydroxybutyrate (cPHB) biosynthesis and chemotaxis in Escherichia coli. The implication of exogenous histamine in the AtoSC-mediated cPHB biosynthesis and in E. coli chemotactic behavior is indicative of a putative function of histamine in bacterial physiology. The data raise questions on the significance of histamine actions in bacteria-host symbiosis, dysbiosis and pathogenicity as well as on the possible consequences upon therapeutic administration of histamine receptor-targeting agents and in particular ligands of the recently identified immunomodulatory H4 receptor.