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Journal of Bacteriology, March 2006, p. 1750-1761, Vol. 188, No. 5
0021-9193/06/$08.00+0     doi:10.1128/JB.188.5.1750-1761.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Involvement of the HP0165-HP0166 Two-Component System in Expression of Some Acidic-pH-Upregulated Genes of Helicobacter pylori

The Membrane Biology Laboratory, Department of Physiology, David Geffen School of Medicine at UCLA, and VA Greater Los Angeles Healthcare System, Los Angeles, California 90073

Received 15 December 2005/ Accepted 20 December 2005

About 200 genes of the gastric pathogen Helicobacter pylori increase expression at medium pHs of 6.2, 5.5, and 4.5, an increase that is abolished or much reduced by the buffering action of urease. Genes up-regulated by a low pH include the two-component system HP0165-HP0166, suggesting a role in the regulation of some of the pH-sensitive genes. To identify targets of HP0165-HP0166, the promoter regions of genes up-regulated by a low pH were grouped based on sequence similarity. Probes for promoter sequences representing each group were subjected to electrophoretic mobility shift assays (EMSA) with recombinant HP0166-His₆ or a mutated response regulator, HP0166-D52N-His₆, that can specifically determine the role of phosphorylation of HP0166 in binding (including a control EMSA with in-vitro-phosphorylated HP0166-His₆). Nineteen of 45 promoter-regulatory regions were found to interact with HP0166-His₆. Seven promoters for genes encoding -carbonic anhydrase, omp11, fecD, lpp20, hypA, and two with unknown function (pHP1397-1396 and pHP0654-0675) were clustered in gene group A, which may respond to changes in the periplasmic pH at a constant cytoplasmic pH and showed phosphorylation-dependent binding in EMSA with HP0166-D52N-His₆. Twelve promoters were clustered in groups B and C whose up-regulation likely also depends on a reduction of the cytoplasmic pH at a medium pH of 5.5 or 4.5. Most of the target promoters in groups B and C showed phosphorylation-dependent binding with HP0166-D52N-His₆, but promoters for ompR (pHP0166-0162), pHP0682-0681, and pHP1288-1289 showed phosphorylation-independent binding. These findings, combined with DNase I footprinting, suggest that HP0165-0166 is an acid-responsive signaling system affecting the expression of pH-sensitive genes. Regulation of these genes responds either to a decrease in the periplasmic pH alone (HP0165 dependent) or also to a decrease in the cytoplasmic pH (HP0165 independent).

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This article has been cited by other articles:

• Scott, D. R., Marcus, E. A., Wen, Y., Oh, J., Sachs, G. (2007). Gene expression in vivo shows that Helicobacter pylori colonizes an acidic niche on the gastric surface. Proc. Natl. Acad. Sci. USA 104: 7235-7240 [Abstract] [Full Text]  
• Wen, Y., Feng, J., Scott, D. R., Marcus, E. A., Sachs, G. (2007). The HP0165-HP0166 Two-Component System (ArsRS) Regulates Acid-Induced Expression of HP1186 {alpha}-Carbonic Anhydrase in Helicobacter pylori by Activating the pH-Dependent Promoter. J. Bacteriol. 189: 2426-2434 [Abstract] [Full Text]