title: Modeling the regulation of the competence-evoking quorum sensing network in Streptococcus pneumoniae.
abstract: Competence for genetic transformation seems to play a fundamental role in the biology of Streptococcus pneumoniae and is believed to account for serotype switching, evolution of virulence factors, and rapid emergence of antibiotic resistance. The initiation of competence is regulated by the quorum sensing system referred as the ComABCDE pathway. Experimental studies reveal that competence is down-regulated a short time after its induction and several hypotheses about the mechanism(s) responsible for this shut-down have been presented. Possibly, a ComX-dependent gene product, such as a repressor or a phosphatase, is involved. To better understand the down-regulation of the competence-evoking system in S. pneumoniae, a mathematical model was set up. By analyzing the model, we suggest that shut-down of competence possibly occurs at the transcriptional level on the comCDE operon. As a result of introducing a putative comX-dependent repressor, which inhibits expression of comCDE and comX, in the mathematical model, competence is demonstrated to appear in waves. This is supported by experimental studies showing the appearance of successive competence cycles in pneumococcal batch cultures.
authors.affiliation: Molecular Biology, School of Life Sciences, University of Skövde, SE-541 28 Skövde, Sweden. diana.karlsson@his.se
authors.forename: Diana
authors.initials: D
authors.lastname: Karlsson
authors.forename: Stefan
authors.initials: S
authors.lastname: Karlsson
authors.forename: Erik
authors.initials: E
authors.lastname: Gustafsson
authors.forename: Birgitta Henriques
authors.initials: BH
authors.lastname: Normark
authors.forename: Patric
authors.initials: P
authors.lastname: Nilsson
mesh_terms: D000942:Antigens, Bacterial; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D008954:Models, Biological; D008957:Models, Genetic; D015233:Models, Statistical; D008962:Models, Theoretical; D009991:Oscillometry; D053038:Quorum Sensing; D012333:RNA, Messenger / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000235:genetics*; D049490:Systems Biology; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D000942:Antigens, Bacterial; D012333:RNA, Messenger