A natural bacterial pathogen of C. elegans uses a small RNA to induce transgenerational inheritance of learned avoidance.
A natural bacterial pathogen of C. elegans uses a small RNA to induce transgenerational inheritance of learned avoidance.
复制标题
线虫的天然细菌病原体使用小 RNA 诱导习得性回避的跨代遗传。
DOI：
10.1101/2023.07.20.549962
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Murphy,ColeenT
中科院分区：
文献类型：
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作者：
Sengupta,Titas;StAnge,Jonathan;Moore,Rebecca;Kaletsky,Rachel;Marogi,Jacob;Myhrvold,Cameron;Gitai,Zemer;Murphy,ColeenT
线虫通过多种机制学会避开病原菌，包括细菌小RNA诱导的习得回避行为，这种行为可以跨代遗传。此前，我们发现来自铜绿假单胞菌临床分离株的小RNA PA14，可诱导线虫习得性回避和跨代遗传。铜绿假单胞菌是重要的人类病原体，在线虫的自然栖息地中还存在其他假单胞菌，但目前尚不清楚线虫是否在野外遇到过类似PA14的细菌。因此，尚不清楚线虫自然栖息地中发现的细菌的小RNA是否也可以调节宿主行为并产生可遗传的行为效应。在这里，我们筛选了一组野生栖息地细菌，发现从线虫微生物群中分离出的致病性假单胞菌GRb0427可以调节蠕虫的行为：蠕虫在暴露后学会避开这种致病细菌，并且这种习得性回避会遗传四代。学习反应完全由细菌产生的小RNA介导，这些小RNA会诱导回避和跨代遗传，进一步支持这种学习和遗传机制在野外存在。我们鉴定了 Pv1，一种在 P.vranovensis 中表达的小 RNA，它与 C.elegansgenemaco-1 的外显子具有 16 个核苷酸匹配。 Pv1 对于诱发 Grb0427 的习得性回避既必要又充分。然而，Pv1 也会导致避免有益微生物菌株门多萨假单胞菌 (P.mendocina)。我们的研究结果表明，细菌小RNA介导的宿主行为调节及其跨代遗传可能在秀丽隐杆线虫的自然环境中发挥作用，并且这种潜在的适应不良反应可能有利于几代后跨代记忆的逆转。我们的数据还表明，不同的细菌小RNA介导的调控系统独立进化，但定义了产生跨代遗传效应的细菌小RNA的共同分子特征。
C.eleganscan learn to avoid pathogenic bacteria through several mechanisms, including bacterial small RNA-induced learned avoidance behavior, which can be inherited transgenerationally. Previously, we discovered that a small RNA from a clinical isolate ofPseudomonas aeruginosa, PA14, induces learned avoidance and transgenerational inheritance of that avoidance inC.elegans.Pseudomonas aeruginosais an important human pathogen, and there are otherPseudomonadsinC.elegans’natural habitat, but it is unclear whetherC.elegansever encounters PA14-like bacteria in the wild. Thus, it is not known if small RNAs from bacteria found inC.elegans’natural habitat can also regulate host behavior and produce heritable behavioral effects. Here we screened a set of wild habitat bacteria, and found that a pathogenicPseudomonas vranovensisstrain isolated from theC.elegansmicrobiota, GRb0427, regulates worm behavior: worms learn to avoid this pathogenic bacterium following exposure, and this learned avoidance is inherited for four generations. The learned response is entirely mediated by bacterially-produced small RNAs, which induce avoidance and transgenerational inheritance, providing further support that such mechanisms of learning and inheritance exist in the wild. We identified Pv1, a small RNA expressed inP.vranovensis, that has a 16-nucleotide match to an exon of theC.elegansgenemaco-1. Pv1 is both necessary and sufficient to induce learned avoidance of Grb0427. However, Pv1 also results in avoidance of a beneficial microbiome strain,P.mendocina. Our findings suggest that bacterial small RNA-mediated regulation of host behavior and its transgenerational inheritance may be functional inC.elegans’natural environment, and that this potentially maladaptive response may favor reversal of the transgenerational memory after a few generations. Our data also suggest that different bacterial small RNA-mediated regulation systems evolved independently, but define shared molecular features of bacterial small RNAs that produce transgenerationally-inherited effects.