A Small Molecule Coordinates Symbiotic Behaviors in a Host Organ.
A Small Molecule Coordinates Symbiotic Behaviors in a Host Organ.
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DOI：
10.1128/mbio.03637-20
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发表时间：
2021-03-09
期刊：
影响因子：
6.4
通讯作者：
Sanchez LM
中科院分区：
文献类型：
--
作者：
Zink KE;Ludvik DA;Lazzara PR;Moore TW;Mandel MJ;Sanchez LM
动物微生物组的复杂性对定义微生物群落内以及微生物与宿主之间的信号分子提出了挑战。通过专注于费氏弧菌和Euprymna peculopes之间的二元共生关系，我们结合遗传分析与直接成像来定义和研究完整共生关系中的小分子。夏威夷短尾乌贼Euprymna candiopes与其微生物共生体Vibrio fischeri之间的终身关系代表了研究微生物组建立和维护的简化模型系统。这种细菌在鱿鱼体内的一个专门的共生光器官中定居，细菌的发光在一个称为反照明的过程中包围宿主。鱿鱼宿主在没有共生体的情况下孵化，共生体必须从海洋中的多种无益细菌中获得，因此需要精确的分子通讯来启动特定关系。因此，很可能在光器官微环境中使用专门的代谢物来调节这些过程。为了鉴定可能影响这种共生关系建立的小分子，我们使用成像质谱分析了具有改变的生物膜产生的费氏弧菌中的代谢物产生，这与其宿主中的定殖能力直接相关。将“生物膜向上”和“生物膜向下”突变体与野生型菌株进行比较，并且检测到由生物膜向上突变体更丰富地产生的离子。使用结构解析和合成化学的组合，一个这样的信号被确定为二酮哌嗪，环（d-组氨酰-L-脯氨酸）。这种二酮哌嗪调制的发光在V. fischeri，并使用成像质谱法，直接检测到在光器官的殖民主机。这项工作强调了在宿主-微生物相互作用中继续进行非靶向发现工作的必要性，并展示了鱿鱼-弧菌系统用于识别和表征调节微生物组行为的小分子的益处。
The complexity of animal microbiomes presents challenges to defining signaling molecules within the microbial consortium and between the microbes and the host. By focusing on the binary symbiosis between Vibrio fischeri and Euprymna scolopes, we have combined genetic analysis with direct imaging to define and study small molecules in the intact symbiosis. The lifelong relationship between the Hawaiian bobtail squid Euprymna scolopes and its microbial symbiont Vibrio fischeri represents a simplified model system for studying microbiome establishment and maintenance. The bacteria colonize a dedicated symbiotic light organ in the squid, from which bacterial luminescence camouflages the host in a process termed counterillumination. The squid host hatches without its symbionts, which must be acquired from the ocean amidst a diversity of nonbeneficial bacteria, such that precise molecular communication is required for initiation of the specific relationship. Therefore it is likely there are specialized metabolites used in the light organ microenvironment to modulate these processes. To identify small molecules that may influence the establishment of this symbiosis, we used imaging mass spectrometry to analyze metabolite production in V. fischeri with altered biofilm production, which correlates directly to colonization capability in its host. “Biofilm-up” and “biofilm-down” mutants were compared to a wild-type strain, and ions that were more abundantly produced by the biofilm-up mutant were detected. Using a combination of structural elucidation and synthetic chemistry, one such signal was determined to be a diketopiperazine, cyclo(d-histidyl-l-proline). This diketopiperazine modulated luminescence in V. fischeri and, using imaging mass spectrometry, was directly detected in the light organ of the colonized host. This work highlights the continued need for untargeted discovery efforts in host-microbe interactions and showcases the benefits of the squid-Vibrio system for identification and characterization of small molecules that modulate microbiome behaviors.