halocidin and Disease-Models--Animal

HG1 is an antimicrobial peptide derived from halocidin, which is naturally found in tunicates. The purpose of this study was to evaluate the therapeutic potential of HG1 as a novel antifungal agent for treating oral candidiasis.. The pharmacokinetic properties of HG1 were explored in mice, which were orally administered a single dose of HG1. Anti-Candida activity of HG1 was investigated in a time-dependent manner in the presence of saliva obtained from healthy donors or patients with oral candidiasis. In addition, HG1 was evaluated for its anti-Candida activity in the presence of proteins extracted from the culture supernatant of Candida albicans. The therapeutic potential in vivo and ex vivo of HG1 against oral candidiasis was investigated using a mouse model of oral candidiasis.. Our data showed that absorption of HG1 into the blood did not occur following oral administration. In addition, HG1 exerted marked anti-Candida activity after short-term incubation at a concentration of 20 mg/L and it also caused a considerable reduction in fungal burden in the oral candidiasis mouse model when treated with 1 mg or 0.5 mg.. This study suggests that HG1, as a novel component of mouthwash, might become an alternative antifungal agent to conventional drugs used to manage oral candidiasis.

Topics: Administration, Oral; Animals; Antifungal Agents; Biological Products; Candida albicans; Candidiasis, Oral; Disease Models, Animal; Female; Mice; Mice, Inbred ICR; Peptides

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.

Topics: Animals; Anti-Bacterial Agents; Blood Cells; Chromatography, High Pressure Liquid; Disease Models, Animal; Dose-Response Relationship, Drug; Hemolysis; Humans; Listeria monocytogenes; Listeriosis; Liver; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Peptides; Spleen; Time Factors