title: Antibacterial activity of a competence-stimulating peptide in experimental sepsis caused by Streptococcus pneumoniae.
abstract: Streptococcus pneumoniae, a major cause of human disease, produces a 17-mer autoinducer peptide pheromone (competence-stimulating peptide [CSP]) for the control of competence for genetic transformation. Due to previous work linking CSP to stress phenotypes, we set up an in vivo sepsis model to assay its effect on virulence. Our data demonstrate a significant increase in the rates of survival of mice, reductions of blood S. pneumoniae counts, and prolonged times to death for mice treated with CSP. In vitro the dose of CSP used in the animal model produced a transitory inhibition of growth. When a mutant with a mutation in the CSP sensor histidine kinase was assayed, no bacteriostatic phenotype was detected in vitro and no change in disease outcome was observed in vivo. The data demonstrate that CSP, which induces in vitro a temporary growth arrest through stimulation of its cognate histidine kinase receptor, is able to block systemic disease in mice. This therapeutic effect is novel, in that the drug-like effect is obtained by stimulation, rather than inhibition, of a bacterial drug target.
authors.affiliation: Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena, Siena, Italy. oggioni@unisi.it
authors.forename: Marco R
authors.initials: MR
authors.lastname: Oggioni
authors.forename: Francesco
authors.initials: F
authors.lastname: Iannelli
authors.forename: Susanna
authors.initials: S
authors.lastname: Ricci
authors.forename: Damiana
authors.initials: D
authors.lastname: Chiavolini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Parigi
authors.forename: Claudia
authors.initials: C
authors.lastname: Trappetti
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Claverys
authors.forename: Gianni
authors.initials: G
authors.lastname: Pozzi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000627:therapeutic use*; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins / Q000627:therapeutic use*; D005260:Female; D000071677:Histidine Kinase; D051379:Mice; D016296:Mutagenesis; D010641:Phenotype; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D011494:Protein Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C061262:ComA protein, Bacteria; D004268:DNA-Binding Proteins; D011494:Protein Kinases; D000071677:Histidine Kinase