title: CinA is regulated via ComX to modulate genetic transformation and cell viability in Streptococcus mutans.
abstract: The Streptococcus mutans ComX-regulon encompasses > 200 mostly uncharacterized genes, including cinA. Here we report that cinA is regulated by ComX in the presence of the competence stimulating peptide (CSP), wherein loss of CinA (strain SmuCinA) results in reduced transformability with or without added CSP by 74- and 15-fold, respectively (P < 0.003). In CSP-supplemented cultures, a two-fold increase in cell viability was noted for SmuCinA relative to UA159 (P < 0.002), suggesting CinA's involvement in the CSP-modulated cell killing response. Relative to UA159, loss of CinA also rendered the mutant hypersensitive to killing by methyl methanesulfonate (MMS), which impairs homologous recombination. Despite our use of a non-polar mutagenesis strategy to knockout cinA, which is the first gene of the multicistronic operon harboring cinA, we noted a drastic reduction in recA expression. By using a CinA-complemented mutant, we were able to partially, but not completely restore all phenotypes to UA159 levels. Complementation results suggested that although cinA participates in modulating competence, viability and MMS tolerance, genes downstream of the cinA transcript may also regulate these phenotypes, a finding that warrants further examination. This is the first report that describes a role for S. mutans' CinA in contending with DNA damage, genetic transformation and cell survival.
authors.affiliation: Dental Research Institute, University of Toronto, Toronto, ON, Canada.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Mair
authors.forename: Dilani B
authors.initials: DB
authors.lastname: Senadheera
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Cvitkovitch
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D061269:DNA Transformation Competence; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D008741:Methyl Methanesulfonate / Q000633:toxicity; D050296:Microbial Viability; D011938:Rec A Recombinases / Q000096:biosynthesis; D011995:Recombination, Genetic; D013295:Streptococcus mutans / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D014170:Transformation, Genetic
chemical_list: D001426:Bacterial Proteins; C120829:ComX protein, Streptococcus; D014157:Transcription Factors; C423628:competence factor, Streptococcus; D008741:Methyl Methanesulfonate; D011938:Rec A Recombinases