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The cia operon of Streptococcus mutans encodes a unique component required for calcium‐mediated autoregulation
Author(s) -
He Xuesong,
Wu Chenggang,
Yarbrough Daniel,
Sim Lucy,
Niu Guoqing,
Merritt Justin,
Shi Wenyuan,
Qi Fengxia
Publication year - 2008
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2008.06390.x
Subject(s) - operon , biology , two component regulatory system , genetics , gene , gal operon , l arabinose operon , microbiology and biotechnology , mutant
Summary Streptococcus mutans is a primary pathogen for dental caries in humans. CiaR and CiaH of S. mutans comprise a two‐component signal transduction system (TCS) involved in regulating various virulent factors. However, the signal that triggers the CiaRH response remains unknown. In this study, we show that calcium is a signal for regulation of the ciaRH operon, and that a double‐glycine‐containing small peptide encoded within the ciaRH operon (renamed ciaX ) mediates this regulation. CiaX contains a serine + aspartate (SD) domain that is shared by calcium‐binding proteins. A markerless in‐frame deletion of ciaX reduced ciaRH operon expression and diminished the calcium repression of operon transcription. Point mutations of the SD domain resulted in the same phenotype as the in‐frame deletion, indicating that the SD domain is required for CiaX function. Further characterization of ciaX demonstrated that it is involved in calcium‐mediated biofilm formation. Furthermore, inactivation of ciaR or ciaH led to the same phenotype as the in‐frame deletion of ciaX , suggesting that all three genes are involved in the same regulatory pathway. Sequence analysis and real‐time RT‐PCR identified a putative CiaR binding site upstream of ciaX . We conclude that the ciaXRH operon is a three‐component, self‐regulatory system modulating cellular functions in response to calcium.