The proline-rich peptide Bac7(1-35) reduces mortality from Salmonella typhimurium in a mouse model of infection.
BACKGROUND
Bac7 is a proline-rich peptide with a potent in vitro antimicrobial activity against Gram-negative bacteria. Here we investigated its activity in biological fluids and in vivo using a mouse model of S. typhimurium infection.


RESULTS
The efficacy of the active 1-35 fragment of Bac7 was assayed in serum and plasma, and its stability in biological fluids analyzed by Western blot and mass spectrometry. The ability of the peptide to protect mice against Salmonella was assayed in a typhoid fever model of infection by determination of survival rates and bacterial load in liver and spleen of infected animals. In addition, the peptide's biodistribution was evaluated by using time-domain optical imaging. Bac7(1-35) retained a substantial in vivo activity showing a very low toxicity. The peptide increased significantly the number of survivors and the mean survival times of treated mice reducing the bacterial load in their organs despite its rapid clearance.


CONCLUSIONS
Our results provide a first indication for a potential development of Bac7-based drugs in the treatment of salmonellosis and, eventually, other Gram-negative infections. The in vivo activity for this peptide might be substantially enhanced by decreasing its excretion rate or modifying the treatment schedule.
Benincasa
Monica
M
Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy. mbenincasa@units.it
Pelillo
Chiara
C
Zorzet
Sonia
S
Garrovo
Chiara
C
Biffi
Stefania
S
Gennaro
Renato
R
Scocchi
Marco
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D008099:Liver / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D012481:Salmonella Infections, Animal / Q000188:drug therapy* / Q000382:microbiology; D012486:Salmonella typhimurium; D013154:Spleen / Q000382:microbiology; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C481640:Bac7(1-35) peptide