Antibacterial activity of the human host defence peptide LL-37 and selected synthetic cationic lipids against bacteria associated with oral and upper respiratory tract infections

人类宿主防御肽 LL-37 和选定的合成阳离子脂质对与口腔和上呼吸道感染相关的细菌的抗菌活性

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作者:Katarzyna Leszczynska, Dorota Namiot, Fitzroy J Byfield, Katrina Cruz, Malgorzata Zendzian-Piotrowska, David E Fein, Paul B Savage, Scott Diamond, Christopher A McCulloch, Paul A Janmey, Robert Bucki

Conclusions

These data suggest that cationic lipids such as ceragenins warrant further testing as potential novel antibacterial agents.

Methods

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.

Results

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. Conclusions: These data suggest that cationic lipids such as ceragenins warrant further testing as potential novel antibacterial agents.

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