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.