Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach
Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach
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DOI：
10.7554/elife.44341
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发表时间：
2019-02-26
期刊：
影响因子：
7.7
通讯作者：
Lemaitre, Bruno
中科院分区：
文献类型：
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作者：
Hanson, Mark Austin;Dostalova, Anna;Lemaitre, Bruno
抗菌肽（Antimicrobial peptides，AMP）是由宿主编码的抗生素，具有抗微生物侵袭的作用。这些短的阳离子肽涉及许多生物过程，主要涉及先天免疫。体外研究表明AMP在生理浓度下杀死细菌和真菌，但在体内几乎没有验证。我们利用CRISPR基因编辑删除了果蝇所有已知的免疫诱导型AMP，即：4种Attacins，4种Cecropins，2种Diptericins，Drosocin，Drosomycin，Metchnikowin和Defensin。使用单个和多个敲除，包括苍蝇缺乏所有14 AMP基因，我们的特点是在体内功能的个人和群体的AMP对不同的细菌和真菌病原体。我们发现，果蝇抗菌肽主要作用于革兰氏阴性细菌和真菌，贡献相加或协同。我们还描述了显着的特异性，其中某些AMP有助于对特定病原体的大部分杀微生物活性，提供功能演示高度特异性AMP-病原体相互作用在体内设置。
Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little validation has been done in vivo. We utilized CRISPR gene editing to delete all known immune-inducible AMPs of Drosophila, namely: 4 Attacins, 4 Cecropins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking all 14 AMP genes, we characterize the in vivo function of individual and groups of AMPs against diverse bacterial and fungal pathogens. We found that Drosophila AMPs act primarily against Gram-negative bacteria and fungi, contributing either additively or synergistically. We also describe remarkable specificity wherein certain AMPs contribute the bulk of microbicidal activity against specific pathogens, providing functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting.