期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 68, 期 3, 页码 610-618出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dks434
关键词
oral infection; microbiological assay; ceragenins; D2S
资金
- NIH [HL67286, HL66565]
- Medical University of Bialystok [3-22574F, 123-22861F]
- Genentech Inc.
We aim to develop antibacterial peptide mimics resistant to protease degradation, with broad-spectrum activity at sites of infection. The bactericidal activities of LL-37, ceragenins CSA-13, CSA-90 and CSA-92 and the spermine-conjugated dexamethasone derivative D2S were evaluated using MIC and MBC measurements. Gingival fibroblast counting, interleukin-8 (IL-8) and lactate dehydrogenase (LDH) release from keratinocytes (HaCat) were used to determine effects on cell growth, pro-inflammatory response and toxicity. All tested cationic lipids showed stronger bactericidal activity than LL-37. Incubation of Staphylococcus aureus with half the MIC of LL-37 led to the appearance of bacteria resistant to its bactericidal effects, but identical incubations with CSA-13 or D2S did not produce resistant bacteria. Cathelicidin LL-37 significantly increased the total number of gingival fibroblasts, but ceragenins and D2S did not alter gingival fibroblast growth. Cationic lipids showed no toxicity to HaCat cells at concentrations resulting in bacterial killing. These data suggest that cationic lipids such as ceragenins warrant further testing as potential novel antibacterial agents.
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