Antimicrobial effect of halocidin-derived peptide in a mouse model of Listeria infection.
Halocidin is an antimicrobial peptide found in the tunicate. A series of experiments were previously conducted in an attempt to develop a novel antibiotic derived from halocidin, as the peptide was determined to evidence profound antimicrobial activity against a variety of antibiotic-resistant microbes, with significantly less toxicity to human blood cells. In this study, we assessed the validity of one of the halocidin congeners, called Khal, as a new antibiotic for the treatment of systemic bacterial infections. Our in vitro antimicrobial tests showed that the MICs of Khal against several gram-positive bacteria were below 16 microg/ml in the presence of salt. We also determined that Khal retained sufficient target selectivity to discern microbial and human blood cells and was therefore capable of efficiently killing invading pathogens. Furthermore, Khal caused no aggregation problems upon incubation with human serum and also proved to be resistant to proteolysis by enzymes occurring in human serum. In the following experiments conducted with a mouse model of Listeria monocytogenes infection, we demonstrated that a single intravenous inoculation with Khal resulted in significant therapeutic effects on the survival of mice. In addition, our bacterial-enumeration analysis showed that after Listeria infection, livers and spleens from Khal-treated mice generated a great deal fewer recoverable CFU. Finally, the antibiotic effects of Khal were evaluated under confocal microscopy after we immunostained the liver sections with anti-Khal antibody. It was concluded that Khal bound specifically to the surfaces of bacteria colonized in the mouse liver and killed the bacteria rapidly.
Jang
Woong Sik
WS
Department of Biotechnology, Hoseo University, 165 Sechuli, Baebangmyun, Asan City, Chungnam 336-795, South Korea.
Lee
Sang-Chul
SC
Lee
Young Shin
YS
Shin
Yong Pyo
YP
Shin
Kyoung Hwa
KH
Sung
Boo Hee
BH
Kim
Byung S
BS
Lee
Soo Han
SH
Lee
In Hee
IH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects / Q000382:microbiology; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008089:Listeria monocytogenes / Q000187:drug effects; D008088:Listeriosis / Q000188:drug therapy* / Q000382:microbiology; D008099:Liver / Q000187:drug effects / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000821:virology; D013997:Time Factors
D000900:Anti-Bacterial Agents; D010455:Peptides; C460842:halocidin