Bacteriophage adhering to mucus provide a non-host-derived immunity
Bacteriophage adhering to mucus provide a non-host-derived immunity
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DOI：
10.1073/pnas.1305923110
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发表时间：
2013-06-25
影响因子：
11.1
通讯作者：
Rohwer, Forest
中科院分区：
文献类型：
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作者：
Barr, Jeremy J.;Auro, Rita;Rohwer, Forest
粘膜表面是病原体的主要入口，也是防御感染的主要部位。细菌和噬菌体都与这种粘液有关。在这里，我们表明噬菌体与细菌的比率相对于邻近环境有所增加，在所有取样的粘膜表面，从刺胞动物到人类。体外对有或无表面黏液的组织培养细胞的研究表明，这种噬菌体丰度的增加依赖于黏液，并保护下层上皮免受细菌感染。黏液中噬菌体的富集是通过黏液蛋白糖蛋白和暴露在噬菌体衣壳上的igg样蛋白结构域的结合相互作用发生的。特别是，噬菌体igg样结构域结合覆盖黏液的粘蛋白糖蛋白成分的可变聚糖残基。宏基因组分析发现，这些igg样蛋白存在于从许多环境中采集的噬菌体中，特别是在粘膜表面附近的位置。基于这些观察，我们提出了噬菌体黏液粘附模型，该模型提供了一种普遍存在的、但非宿主来源的、适用于粘膜表面的免疫。该模型表明，后生动物的粘膜表面和噬菌体共同进化以维持噬菌体的粘附。这通过限制粘膜细菌使后生动物宿主受益，并通过与细菌宿主更频繁的相互作用使噬菌体受益。这里显示的关系表明噬菌体和后生动物宿主之间的共生关系提供了一种以前未被识别的抗菌防御，积极保护粘膜表面。
Mucosal surfaces are a main entry point for pathogens and the principal sites of defense against infection. Both bacteria and phage are associated with this mucus. Here we show that phage-to-bacteria ratios were increased, relative to the adjacent environment, on all mucosal surfaces sampled, ranging from cnidarians to humans. In vitro studies of tissue culture cells with and without surface mucus demonstrated that this increase in phage abundance is mucus dependent and protects the underlying epithelium from bacterial infection. Enrichment of phage in mucus occurs via binding interactions between mucin glycoproteins and Ig-like protein domains exposed on phage capsids. In particular, phage Ig-like domains bind variable glycan residues that coat the mucin glycoprotein component of mucus. Metagenomic analysis found these Ig-like proteins present in the phages sampled from many environments, particularly from locations adjacent to mucosal surfaces. Based on these observations, we present the bacteriophage adherence to mucus model that provides a ubiquitous, but non-host-derived, immunity applicable to mucosal surfaces. The model suggests that metazoan mucosal surfaces and phage co-evolve to maintain phage adherence. This benefits the metazoan host by limiting mucosal bacteria, and benefits the phage through more frequent interactions with bacterial hosts. The relationships shown here suggest a symbiotic relationship between phage and metazoan hosts that provides a previously unrecognized antimicrobial defense that actively protects mucosal surfaces.