Augmentation of Cationic Antimicrobial Peptide Production with Histone Deacetylase Inhibitors as a Novel Epigenetic Therapy for Bacterial Infections.
Augmentation of Cationic Antimicrobial Peptide Production with Histone Deacetylase Inhibitors as a Novel Epigenetic Therapy for Bacterial Infections.
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DOI：
10.3390/antibiotics4010044
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发表时间：
2015-01-12
期刊：
影响因子：
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通讯作者：
Jerse AE
中科院分区：
文献类型：
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作者：
Yedery RD;Jerse AE
抗生素耐药性的出现严重威胁到我们治疗许多常见和医学上重要的细菌感染的能力。需要能够单独使用或与抗生素联合使用的新型治疗方法。阳离子抗菌肽（camp）是宿主先天防御的重要效应物，对多种微生物具有广谱活性。camp在吞噬颗粒中携带，并由多种细胞类型组成或诱导表达，包括上皮细胞。组蛋白修饰酶，特别是组蛋白去乙酰化酶（HDAC）在下调CAMP编码基因转录中的作用，以及HDAC抑制剂（HDACi）阻断HDAC增加CAMP表达的能力，越来越受到人们的重视。因此，使用合成和天然hdac分子来增加粘膜表面的camp具有潜在的治疗应用。在这里，我们回顾了宿主和病原体通过诱导hdac对CAMP表达的调节，并基于组织培养系统、动物模型和临床试验的证据评估了天然和合成hdac的治疗潜力。
The emergence of antibiotic resistance seriously threatens our ability to treat many common and medically important bacterial infections. Novel therapeutics are needed that can be used alone or in conjunction with antibiotics. Cationic antimicrobial peptides (CAMPs) are important effectors of the host innate defense that exhibit broad-spectrum activity against a wide range of microorganisms. CAMPs are carried within phagocytic granules and are constitutively or inducibly expressed by multiple cell types, including epithelial cells. The role of histone modification enzymes, specifically the histone deacetylases (HDAC), in down-regulating the transcription of CAMP-encoding genes is increasingly appreciated as is the capacity of HDAC inhibitors (HDACi) to block the action of HDACs to increase CAMP expression. The use of synthetic and natural HDACi molecules to increase CAMPs on mucosal surfaces, therefore, has potential therapeutic applications. Here, we review host and pathogen regulation of CAMP expression through the induction of HDACs and assess the therapeutic potential of natural and synthetic HDACi based on evidence from tissue culture systems, animal models, and clinical trials.