title: The ParB-parS Chromosome Segregation System Modulates Competence Development in Streptococcus pneumoniae.
abstract: ParB proteins bind centromere-like DNA sequences called parS sites and are involved in plasmid and chromosome segregation in bacteria. We previously showed that the opportunistic human pathogen Streptococcus pneumoniae contains four parS sequences located close to the origin of replication which are bound by ParB. Using chromatin immunoprecipitation (ChIP), we found here that ParB spreads out from one of these parS sites, parS(-1.6°), for more than 5 kb and occupies the nearby comCDE operon, which drives competence development. Competence allows S. pneumoniae to take up DNA from its environment, thereby mediating horizontal gene transfer, and is also employed as a general stress response. Mutating parS(-1.6°) or deleting parB resulted in transcriptional up-regulation of comCDE and ssbB (a gene belonging to the competence regulon), demonstrating that ParB acts as a repressor of competence. However, genome-wide transcription analysis showed that ParB is not a global transcriptional regulator. Different factors, such as the composition of the growth medium and antibiotic-induced stress, can trigger the sensitive switch driving competence. This work shows that the ParB-parS chromosome segregation machinery also influences this developmental process.
  
  
  OBJECTIVE
  Streptococcus pneumoniae (pneumococcus) is an important human pathogen responsible for more than a million deaths each year. Like all other organisms, S. pneumoniae must be able to segregate its chromosomes properly. Not only is understanding the molecular mechanisms underlying chromosome segregation in S. pneumoniae therefore of fundamental importance, but also, this knowledge might offer new leads for ways to target this pathogen. Here, we identified a link between the pneumococcal chromosome segregation system and the competence-developmental system. Competence allows S. pneumoniae to take up and integrate exogenous DNA in its chromosome. This process plays a crucial role in successful adaptation to--and escape from--host defenses, antibiotic treatments, and vaccination strategies. We show that the chromosome segregation protein ParB acts as a repressor of competence. To the best of our knowledge, this is the first example of a ParB protein controlling bacterial competence.
authors.affiliation: Molecular Genetics Group, Centre for Synthetic Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Attaiech
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Minnen
authors.affiliation: Molecular Genetics Group, Centre for Synthetic Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands.
authors.forename: Morten
authors.initials: M
authors.lastname: Kjos
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gruber
authors.affiliation: Molecular Genetics Group, Centre for Synthetic Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands j.w.veening@rug.nl.
authors.forename: Jan-Willem
authors.initials: JW
authors.lastname: Veening
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D020090:Chromosome Segregation; D061269:DNA Transformation Competence; D023061:Gene Order; D008954:Models, Biological; D009876:Operon; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; C103179:ComE protein, Streptococcus pneumoniae; D012097:Repressor Proteins; C052883:chromosome partition proteins, bacterial; C423628:competence factor, Streptococcus