Antibacterial activity of a competence-stimulating peptide in experimental sepsis caused by Streptococcus pneumoniae

Marco R. Oggioni, Francesco Iannelli, Susanna Ricci, Damiana Chiavolini, Riccardo Parigi, Claudia Trappetti, Jean Pierre Claverys, Gianni Pozzi

Research output: Contribution to journalArticle

55 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4725-4732
Number of pages8
JournalAntimicrobial agents and chemotherapy
Volume48
Issue number12
DOIs
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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