Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Curr Biol. 2010 Jan 12;20(1):69-74. doi: 10.1016/j.cub.2009.10.059.
Bacteria belonging to the genera Photorhabdus and Xenorhabdus participate in a trilateral symbiosis in which they enable their nematode hosts to parasitize insect larvae. The bacteria switch from persisting peacefully in a nematode's digestive tract to a lifestyle in which pathways to produce insecticidal toxins, degrading enzymes to digest the insect for consumption, and antibiotics to ward off bacterial and fungal competitors are activated. This study addresses three questions: (1) What molecular signal triggers antibiotic production in the bacteria? (2) What small molecules are regulated by the signal? And (3), how do the bacteria recognize the signal? Differential metabolomic profiling in Photorhabdus luminescens TT01 and Xenorhabdus nematophila revealed that L-proline in the insect's hemolymph initiates a metabolic shift. Small molecules known to be crucial for virulence and antibiosis in addition to previously unknown metabolites are dramatically upregulated by L-proline, linking the recognition of host environment to bacterial metabolic regulation. To identify the L-proline-induced signaling pathway, we deleted the proline transporters putP and proU in P. luminescens TT01. Studies of these strains support a model in which acquisition of L-proline both regulates the metabolic shift and maintains the bacterial proton motive force that ultimately regulates the downstream bacterial pathways affecting virulence and antibiotic production.
属于 Photorhabdus 和 Xenorhabdus 属的细菌参与三方共生关系，使它们的线虫宿主能够寄生昆虫幼虫。细菌从在线虫消化道中和平生存的状态转变为激活途径以产生杀虫毒素、消化昆虫以供食用的降解酶以及抵御细菌和真菌竞争者的抗生素的生活方式。本研究解决了三个问题：（1）什么分子信号触发细菌产生抗生素？（2）哪些小分子受信号调节？以及（3）细菌如何识别信号？在 Photorhabdus luminescens TT01 和 Xenorhabdus nematophila 中的差异代谢组学分析表明，昆虫血液中的 L-脯氨酸引发了代谢转变。除了先前未知的代谢物外，已知对毒力和抗生性至关重要的小分子也被 L-脯氨酸显著上调，将宿主环境的识别与细菌代谢调节联系起来。为了鉴定 L-脯氨酸诱导的信号通路，我们在 P. luminescens TT01 中删除了脯氨酸转运蛋白 putP 和 proU。对这些菌株的研究支持这样一种模型，即 L-脯氨酸的获取既调节代谢转变，又维持细菌质子动力，最终调节影响毒力和抗生素产生的下游细菌途径。
