title: The ciaR/ciaH regulatory network of Streptococcus pneumoniae.
abstract: New mechanisms for beta-lactam resistance independent on the target penicillin-binding proteins were detected in beta-lactam-resistant laboratory mutants of Streptococcus pneumoniae. The link between mutations in the histidine protein kinase CiaH and phenotypic expression of cefotaxime resistance suggests that the cell is able to monitor the integrity of the cell wall and in emergency cases such as during the action of beta-lactams can counteract such danger. At least one ciaH mutation Thr230 > Pro is likely to affect its phosphatase activity resulting in elevated phosphorylation of CiaR, the cognate response regulator, but other CiaH-independent signaling pathways may also result in CiaR phosphorylation. Mutants in CiaH, either alone or in combination with a mutated penicillin-binding protein 2x(PBP2x) fail to develop genetic competence. In all cases complementation of this phenotype was observed upon addition of the competence inducing pheromone peptide CSP, the processed product of the comC gene. This indicates that the cia system is part of a regulatory network that includes another two component system comDE. The DNA binding property of CiaR and ComE were exploited to isolate specifically interacting DNA fragments as a first step to identify genes targeted by individual response regulators.
authors.affiliation: University of Kaiserslautern, Department of Microbiology, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Zähner
authors.forename: Kristina
authors.initials: K
authors.lastname: Kaminski
authors.forename: Mark
authors.initials: M
authors.lastname: van der Linden
authors.forename: Thorsten
authors.initials: T
authors.lastname: Mascher
authors.forename: Michelle
authors.initials: M
authors.lastname: Meral
authors.forename: Regine
authors.initials: R
authors.lastname: Hakenbeck
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D000071677:Histidine Kinase; D007769:Lactams / Q000494:pharmacology; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018440:beta-Lactam Resistance / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D007769:Lactams; D011494:Protein Kinases; D000071677:Histidine Kinase; C088910:CiaR protein, Streptococcus pneumoniae