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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Coordinate expression of the Porphyromonas gingivalis lysine-specific gingipain proteinase, Kgp, arginine-specific gingipain proteinase, RgpA, and the heme/hemoglobin receptor, HmuR

Xinyan Liu1 / Aneta Sroka2 / Jan Potempa3 / Caroline Attardo Genco4

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Corresponding author e-mail:

Citation Information: Biological Chemistry. Volume 385, Issue 11, Pages 1049–1057, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2004.136, June 2005

Publication History

Received:
August 11, 2004
Accepted:
September 29, 2004
Published Online:
2005-06-01

Abstract

Heme utilization in Porphyromonas gingivalis requires the participation of an outer membrane hemin/hemoglobin receptor, HmuR, the lysine-specific gingipain proteinase (Kgp) and arginine-specific gingipain proteinase (Rgp). In this study, the expression of hmuR, kgp and rgpA genes in response to growth with different heme sources was examined by reverse transcription-polymerase chain reaction and enzyme-linked immunoassay. Coordinate regulation of hmuR, kgp and rgpA gene expression was evaluated through utilization of P. gingivalis hmuR and kgp mutants or by selective inactivation of proteinases with Kgp- and Rgp-specific inhibitors. We observed that expression of the kgp and rgpA genes was not tightly regulated by heme, but rather by the growth phase. In contrast, expression of the hmuR gene was negatively regulated by heme, while growth of P. gingivalis with human serum resulted in increased hmuR expression. A P. gingivalis kgp isogenic mutant demonstrated significantly increased hmuR gene expression, and inactivation of Kgp and Rgp activity by specific inhibitors up-regulated hmuR gene transcription. Moreover, inactivation of Kgp up-regulated rgpA transcription. Finally, a P. gingivalis hmuR mutant exhibited repressed kgp gene expression and lysine-specific proteinase activity. Collectively, these results indicate that kgp, rgpA and hmuR gene transcription is coordinately regulated and may facilitate greater efficiency of heme utilization in P. gingivalis.

Keywords: gene expression; gingipains; heme receptor; Porphyromonas gingivalis

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