In vitro and in vivo antimicrobial activity of granulysin-derived peptides against Vibrio cholerae.
OBJECTIVE
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.
da Silva
Ana Paula Galvão
AP
Division of Immunology and Transplantation Biology, Department of Pediatrics, CCSR 2105, Stanford University School of Medicine, Stanford, CA 94305, USA.
Unks
Donovan
D
Lyu
Shu-chen
SC
Ma
Jeffrey
J
Zbozien-Pacamaj
Renata
R
Chen
Xi
X
Krensky
Alan M
AM
Clayberger
Carol
C
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry / Q000494:pharmacology*; D002771:Cholera / Q000188:drug therapy; D007422:Intestines / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D014734:Vibrio cholerae / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human