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Open Access Highly Accessed Research article

The proline-rich peptide Bac7(1-35) reduces mortality from Salmonella typhimurium in a mouse model of infection

Monica Benincasa1, Chiara Pelillo1, Sonia Zorzet1, Chiara Garrovo2, Stefania Biffi2, Renato Gennaro1 and Marco Scocchi1*

Author Affiliations

1 Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy

2 Optical Imaging Laboratory, CBM, Area Science Park, Trieste, Italy

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BMC Microbiology 2010, 10:178  doi:10.1186/1471-2180-10-178

Published: 23 June 2010

Abstract

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.