title: The cia operon of Streptococcus mutans encodes a unique component required for calcium-mediated autoregulation.
abstract: 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.
authors.affiliation: UCLA School of Dentistry, Los Angeles, CA 90095, USA.
authors.forename: Xuesong
authors.initials: X
authors.lastname: He
authors.forename: Chenggang
authors.initials: C
authors.lastname: Wu
authors.forename: Daniel
authors.initials: D
authors.lastname: Yarbrough
authors.forename: Lucy
authors.initials: L
authors.lastname: Sim
authors.forename: Guoqing
authors.initials: G
authors.lastname: Niu
authors.forename: Justin
authors.initials: J
authors.lastname: Merritt
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Shi
authors.forename: Fengxia
authors.initials: F
authors.lastname: Qi
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics*; D018441:Biofilms; D002118:Calcium / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D006706:Homeostasis; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009876:Operon; D010641:Phenotype; D017354:Point Mutation; D012329:RNA, Bacterial / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D015398:Signal Transduction; D013295:Streptococcus mutans / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D002118:Calcium