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J. Bacteriol. doi:10.1128/JB.01742-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A pair of highly conserved two-component systems participates in the regulation of the hyper variable FIR proteins in different Legionella species

Michal Feldman and Gil Segal*

Department of Molecular Microbiology & Biotechnology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat-Aviv, Tel-Aviv 69978, Israel

* To whom correspondence should be addressed. Email: gils{at}tauex.tau.ac.il.


   Abstract

Legionella pneumophila and other pathogenic Legionella species multiply inside protozoa and human macrophages using the Icm/Dot type-IV secretion system. The IcmQ protein which possesses pore forming activity and IcmR which functions as its chaperone are two essential components of this system. It was previously shown that in twenty-nine Legionella species, a large hyper-variable gene family (fir genes) is located upstream from a conserved icmQ gene, but although non-homologous, the FIR proteins were found to function similarly together with their corresponding IcmQ proteins. Alignment of the regulatory regions of twenty-nine fir genes revealed that they can be divided into three regulatory groups; the first group contains a binding site for the CpxR response regulator which was previously shown to regulate the L. pneumophila fir gene (icmR); the second group, which includes most of the fir genes, contains the CpxR binding site and an additional regulatory element that was identified here as a PmrA binding site; and the third group contains only the PmrA binding site. Analysis of the regulatory region of two fir genes, which included substitutions in the CpxR and PmrA consensus sequences, a controlled expression system, as well as examination of direct binding using mobility shift assays, revealed that both CpxR and PmrA positively regulate the expression of the fir genes that contain both regulatory elements. The change in the regulation of the fir genes that occurred during the course of evolution might be required for the adaptation of the different Legionella species to their specific environmental host.




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