Abstract:
: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.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Jang WS,Lee SC,Lee YS,Shin YP,Shin KH,Sung BH,Kim BS,Lee SH,Lee IHdoi
10.1128/AAC.00635-07subject
Has Abstractpub_date
2007-11-01 00:00:00pages
4148-56issue
11eissn
0066-4804issn
1098-6596pii
AAC.00635-07journal_volume
51pub_type
杂志文章abstract::Single nucleotide polymorphisms (SNPs) involved in the development of resistance represent powerful markers for the rapid detection of first- and second-line resistance in clinical Mycobacterium tuberculosis complex (MTBC) isolates. However, the association between particular mutations and phenotypic resistance is not...
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journal_title:Antimicrobial agents and chemotherapy
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