Antibacterial activity of a competence-stimulating peptide in experimental sepsis caused by Streptococcus pneumoniae.
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.
Oggioni
Marco R
MR
Laboratorio di Microbiologia Molecolare e Biotecnologia, Dipartimento di Biologia Molecolare, Università di Siena, Siena, Italy. oggioni@unisi.it
Iannelli
Francesco
F
Ricci
Susanna
S
Chiavolini
Damiana
D
Parigi
Riccardo
R
Trappetti
Claudia
C
Claverys
Jean-Pierre
JP
Pozzi
Gianni
G
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
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C061262:ComA protein, Bacteria; D004268:DNA-Binding Proteins; D011494:Protein Kinases; D000071677:Histidine Kinase