Title: | Antibacterial activity of a competence-stimulating peptide in experimental sepsis caused by Streptococcus pneumoniae |
Author(s): | Oggioni MR; Iannelli F; Ricci S; Chiavolini D; Parigi R; Trappetti C; Claverys JP; Pozzi G; |
Address: | "Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Universita di Siena, Siena, Italy. oggioni@unisi.it" |
Journal Title: | Antimicrob Agents Chemother |
DOI: | 10.1128/AAC.48.12.4725-4732.2004 |
ISSN/ISBN: | 0066-4804 (Print) 1098-6596 (Electronic) 0066-4804 (Linking) |
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 Anti-Bacterial Agents/*therapeutic use Bacterial Proteins/*therapeutic use Colony-Forming Units Assay DNA-Binding Proteins/*therapeutic use Female Histidine Kinase Mice Mutagenesis Phenotype Pneumococcal Infections/*drug therapy/microbiology Prote; |
Notes: | "MedlineOggioni, Marco R Iannelli, Francesco Ricci, Susanna Chiavolini, Damiana Parigi, Riccardo Trappetti, Claudia Claverys, Jean-Pierre Pozzi, Gianni eng Research Support, Non-U.S. Gov't 2004/11/25 Antimicrob Agents Chemother. 2004 Dec; 48(12):4725-32. doi: 10.1128/AAC.48.12.4725-4732.2004" |