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|Title:||Antibacterial activity of a competence-stimulating peptide in experimental sepsis caused by Streptococcus pneumoniae|
|Citation:||Antimicrobial Agents and Chemotherapy, 2004; 48(12):4725-4732|
|Publisher:||Amer Soc Microbiology|
|Marco R. Oggioni, Francesco Iannelli, Susanna Ricci, Damiana Chiavolini, Riccardo Parigi, Claudia Trappetti, Jean-Pierre Claverys, and Gianni Pozzi|
|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.|
|Keywords:||Animals; Mice; Streptococcus pneumoniae; Pneumococcal Infections; Sepsis; Protein Kinases; Bacterial Proteins; DNA-Binding Proteins; Anti-Bacterial Agents; Colony-Forming Units Assay; Reverse Transcriptase Polymerase Chain Reaction; Mutagenesis; Phenotype; Female; Histidine Kinase|
|Description:||Copyright © 2004, American Society for Microbiology. All Rights Reserved.|
|Appears in Collections:||Molecular and Biomedical Science publications|
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