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Antimicrobial Agents and Chemotherapy, December 2004, p. 4725-4732, Vol. 48, No. 12
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.12.4725-4732.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Antibacterial Activity of a Competence-Stimulating Peptide in Experimental Sepsis Caused by Streptococcus pneumoniae

Marco R. Oggioni,1,2* Francesco Iannelli,1 Susanna Ricci,1 Damiana Chiavolini,1 Riccardo Parigi,1 Claudia Trappetti,1 Jean-Pierre Claverys,3 and Gianni Pozzi1,2

Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena,1 UOC Batteriologia, Azienda Ospedaliera Universitaria Senese, Siena, Italy,2 Laboratoire de Microbiologie et de Génétique Moléculaires, UMR5100 CNRS-Université Paul Sabatier, Toulouse, France3

Received 20 April 2004/ Returned for modification 11 July 2004/ Accepted 29 August 2004

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.

* Corresponding author. Mailing address: LAMMB (Laboratorio di Microbiologia Molecolare e Biotecnologia), Policlinico LeScotte (lotto 5, piano 1), 53100 Siena, Italy. Phone: 0039 0577 233101. Fax: 0039 0577 233334. E-mail: oggioni{at}unisi.it.

Antimicrobial Agents and Chemotherapy, December 2004, p. 4725-4732, Vol. 48, No. 12
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.12.4725-4732.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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