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, Carol Clayberger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1103-1109
Number of pages7
JournalJournal of antimicrobial chemotherapy
Volume61
Issue number5
DOIs
StatePublished - May 2008

Funding

This work was supported by NIH grant U19 AI056548 (to C. C.). A. M. K. is the Shelagh Galligan Professor of Pediatrics.

Keywords

  • Antimicrobial peptides
  • Cholera
  • V. cholerae

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)
  • Pharmacology

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