Derivatives of the Mouse Cathelicidin-Related Antimicrobial Peptide (CRAMP) Inhibit Fungal and Bacterial Biofilm Formation
Derivatives of the Mouse Cathelicidin-Related Antimicrobial Peptide (CRAMP) Inhibit Fungal and Bacterial Biofilm Formation
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DOI：
10.1128/aac.03045-14
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发表时间：
2014-09-01
影响因子：
4.9
通讯作者：
Thevissen, Karin
中科院分区：
文献类型：
--
作者：
De Brucker, Katrijn;Delattin, Nicolas;Thevissen, Karin
我们在小鼠胰腺的朗格汉斯胰岛中发现了一种含有26个氨基酸的34个氨基酸的抗菌肽（CRAMP）的截断形式。该肽P318与LL-37人抗菌肽有67%的相似性。由于LL-37具有抗菌和抗膜活性，我们测试了P318对白色念珠菌的抗真菌和抗膜活性。在0.15 μ M浓度下，P318抑制白色念珠菌生物膜的形成，而不影响浮游生物的存活，显示出生物膜特异性活性。接下来，我们测试了一系列截断的P318和丙氨酸取代衍生物的白色假丝酵母菌生物膜抑制活性。根据这些衍生物的生物膜抑制活性和肽的长度，我们决定合成位于10位的缩短的丙氨酸取代肽（AS10; KLKKIAQKIKN FFQKLVP）。AS10在0.22 μ M抑制白色念珠菌生物膜的形成，并与两性霉素B和caspofungin协同作用，抑制成熟生物膜。AS10还抑制不同细菌以及混合生物膜中真菌和细菌的生物膜形成。此外，AS10不会影响参与种植体骨整合的不同类型细胞的活力或功能，这表明AS10有可能进一步发展为覆盖种植体的导联肽。
We identified a 26-amino-acid truncated form of the 34-amino-acid cathelicidin-related antimicrobial peptide (CRAMP) in the islets of Langerhans of the murine pancreas. This peptide, P318, shares 67% identity with the LL-37 human antimicrobial peptide. As LL-37 displays antimicrobial and antibiofilm activity, we tested antifungal and antibiofilm activity of P318 against the fungal pathogen Candida albicans. P318 shows biofilm-specific activity as it inhibits C. albicans biofilm formation at 0.15 mu M without affecting planktonic survival at that concentration. Next, we tested the C. albicans biofilm-inhibitory activity of a series of truncated and alanine-substituted derivatives of P318. Based on the biofilm-inhibitory activity of these derivatives and the length of the peptides, we decided to synthesize the shortened alanine-substituted peptide at position 10 (AS10; KLKKIAQKIKN FFQKLVP). AS10 inhibited C. albicans biofilm formation at 0.22 mu M and acted synergistically with amphotericin B and caspofungin against mature biofilms. AS10 also inhibited biofilm formation of different bacteria as well as of fungi and bacteria in a mixed biofilm. In addition, AS10 does not affect the viability or functionality of different cell types involved in osseointegration of an implant, pointing to the potential of AS10 for further development as a lead peptide to coat implants.