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JAC Advance Access originally published online on February 29, 2008
Journal of Antimicrobial Chemotherapy 2008 61(5):1103-1109; doi:10.1093/jac/dkn058
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

In vitro and in vivo antimicrobial activity of granulysin-derived peptides against Vibrio cholerae

Ana Paula Galvão da Silva, Donovan Unks, Shu-chen Lyu, Jeffrey Ma, Renata Zbozien-Pacamaj, Xi Chen, Alan M. Krensky{dagger} and Carol Clayberger*,{dagger}

Division of Immunology and Transplantation Biology, Department of Pediatrics, CCSR 2105, Stanford University School of Medicine, Stanford, CA 94305, USA

Received 20 September 2007; returned 26 November 2007; revised 14 January 2008; accepted 24 January 2008

* Corresponding author. Tel: +1-301-594-7917; Fax: +1-301-496-8479; E-mail: claybergerc{at}mail.nih.gov

Objectives: To determine the antibacterial activity of synthetic peptides derived from the cationic antimicrobial peptide granulysin against Vibrio cholerae.

Methods: The antibacterial activity of granulysin-derived peptides was assessed in vitro by microtitre and cfu assays. Toxicity against human peripheral blood mononuclear cells (PBMCs) was measured by propidium iodide uptake and haemolysis by measuring the levels of haemoglobin released after incubation of red blood cells (RBCs) with granulysin peptides. The ability of granulysin peptides to control bacterial growth in vivo was tested by the treatment of suckling mice infected with V. cholerae with granulysin peptides, administered by gavage 1 h after infection and determining the number of bacteria in the small and large intestines 24 h after infection.

Results: All peptides tested inhibited V. cholerae growth in vitro, and they were more effective against stationary phase cells. Two peptides, G12.21 and G14.15, effectively controlled bacterial growth in vivo. The peptides did not lyse RBCs and, with the exception of two peptides, exhibited very little toxicity against human PBMCs.

Conclusions: These results suggest that granulysin-derived peptides are candidates for the development of new agents for the treatment of V. cholerae infection.

Keywords: V. cholerae , antimicrobial peptides , cholera

{dagger} Present address. Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA.


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