A novel hydroxyapatite-binding antimicrobial peptide against oral biofilms
A novel hydroxyapatite-binding antimicrobial peptide against oral biofilms
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一种新型羟基磷灰石结合抗口腔生物膜抗菌肽
DOI：
10.1007/s00784-018-2701-x
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发表时间：
2019-06-01
影响因子：
3.4
通讯作者：
Shen, Ya
中科院分区：
文献类型：
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作者：
Yang, Yan;Xia, Lingyun;Shen, Ya
目的开发新型合成抗菌肽，由新型免疫调节肽 1018 和两种具有羟基磷灰石结合亲和力的不同修饰组成。我们比较了这些肽对口腔菌斑生物膜的作用，并测量了它们在杀死生物膜微生物和减少生物膜体积方面的有效性。材料和方法高亲和力羟基磷灰石 (HA) 结合肽 1018 (SHABP)、温和亲和力 HA 结合肽 1018 (MHABP) 和不含额外氨基的肽 1018 合成了酸序列（肽1018）。口腔多物种生物膜在厌氧条件下生长 3 天。将生物膜暴露于两种不同浓度（0.65 和 3.25 μmol/L）的三种肽中 24、48 和 72 小时。生物膜还用肽 (3.25 μmol/L) 处理 3 或 9 分钟。通过 LIVE/DEAD 活力染色和共聚焦激光扫描显微镜测定被杀死的生物膜细菌的百分比和生物膜体积。结果SHABP 对预先形成的生物膜的杀灭效果优于 MHABP 和肽 1018，特别是在浓度为 3.25 μmol/L 时 (p< 0.05)。在两种浓度下，SHABP 在减少总体生物膜体积方面也优于 MHABP 和肽 1018 (p< 0.05)。在 3 天的长期暴露过程中，MHABP 和肽 1080 杀死了生物膜上半部分的细菌，而不是下半部分的细菌。第 1 天，SHABP 杀死的生物膜下半部 (39%) 细菌多于上半部 (29%) (p< 0.05)，而第 2 天和第 3 天，上层杀死的细菌更多。与高浓度的 MHABP 或肽 1018 相比，在 3 天的生物膜上使用 1 次或 3 次，每次 3 分钟，SHABP 杀死的菌斑生物膜细菌百分比要高得多 (p< 0.05)。结论具有高 HA 结合亲和力的修饰肽 1018 对生物膜微生物具有更高的抗菌活性，并且比其他测试的肽更能减少生物膜体积。临床相关性具有高羟基磷灰石结合亲和力的修饰肽 1018 是未来用于口腔抗生物膜策略的有前途的药物。
ObjectivesNovel synthetic antimicrobial peptides which consist of a new immunomodulatory peptide 1018 and two different modifications with hydroxyapatite-binding affinity were developed. We compared the effect(s) of these peptides against oral plaque biofilms and measured their effectiveness in killing biofilm microbes and in reducing biofilm volume.Materials and methodsThe high affinity hydroxyapatite (HA)-binding peptide 1018 (SHABP), the mild affinity HA-binding peptide 1018 (MHABP), and peptide 1018 without additional amino acid sequence (peptide 1018) were synthesized. Oral multispecies biofilms were grown anaerobically for 3 days. The biofilms were exposed to three peptides at two different concentrations (0.65 and 3.25 μmol/L) for 24, 48, and 72 h. The biofilms were also treated for 3 or 9 min with the peptides (3.25 μmol/L). The percentage of killed biofilm bacteria and biofilm volume were determined by using LIVE/DEAD viability staining and confocal laser scanning microscopy.ResultsSHABP was superior to MHABP and peptide 1018 in its killing efficacy of the pre-formed biofilms, especially at concentration of 3.25 μmol/L (p< 0.05). SHABP performed also better than MHABP and peptide 1018 in reducing the overall biofilm volume at both concentrations (p< 0.05). During the 3 days of long-term exposure, MHABP and peptide 1080 killed more bacteria in the top half of the biofilms, compared to bottom half. SHABP killed more bacteria in the bottom half (39%) of the biofilms than in the top half (29%) at day 1 (p< 0.05), whereas more bacteria were killed in the upper layers on days 2 and 3. SHABP killed a much higher percentage of plaque biofilm bacteria when used on 3-day-old biofilms for one or three times for 3 min than MHABP or peptide 1018 at high concentration (p< 0.05).ConclusionsThe modified peptide 1018 with high HA-binding affinity had higher antimicrobial activity against biofilm microbes and reduced biofilm volume more than the other peptides tested.Clinical relevanceModified peptide 1018 with high hydroxyapatite-binding affinity is a promising agent for use in oral antibiofilm strategies in the future.