The bacterial toxin colibactin triggers prophage induction.
The bacterial toxin colibactin triggers prophage induction.
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DOI：
10.1038/s41586-022-04444-3
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发表时间：
2022-03
期刊：
影响因子：
64.8
通讯作者：
Balskus EP
中科院分区：
文献类型：
--
作者：
Silpe JE;Wong JWH;Owen SV;Baym M;Balskus EP
Colibactin是一种化学上不稳定的小分子遗传毒素，由几种不同的细菌产生，包括人类肠道微生物组的成员。虽然大肠杆菌素的生物活性已在哺乳动物系统中进行了广泛的研究，但对其对其他微生物的影响知之甚少。在这里，我们表明，大肠杆菌素的目标细菌含有原噬菌体，并诱导裂解发展通过细菌SOS反应。外源添加的DNA保护细菌免受大肠杆菌素的侵害，就像在非大肠杆菌素产生细胞中表达大肠杆菌素抗性蛋白（ClbS）一样。我们观察到的原噬菌体诱导效应广泛适用于不同的噬菌体细菌系统和复杂的社区。最后，我们确定了具有大肠杆菌素抗性基因但缺乏大肠杆菌素生物合成基因的细菌。许多这些细菌感染预测的原噬菌体，我们表明，他们的ClbS同源物的表达提供免疫大肠杆菌素触发诱导。我们的研究揭示了大肠杆菌素生产可能影响微生物组的机制，并强调了微生物天然产物在影响人群水平事件（如噬菌体爆发）中的作用。细菌基因毒素大肠杆菌素触发邻近细菌的原噬菌体介导的裂解，这一发现提供了对微生物群落动态以及细菌代谢产物产生和噬菌体行为之间关系的深入了解。
Colibactin is a chemically unstable small-molecule genotoxin that is produced by several different bacteria, including members of the human gut microbiome. Although the biological activity of colibactin has been extensively investigated in mammalian systems, little is known about its effects on other microorganisms. Here we show that colibactin targets bacteria that contain prophages, and induces lytic development through the bacterial SOS response. DNA, added exogenously, protects bacteria from colibactin, as does expressing a colibactin resistance protein (ClbS) in non-colibactin-producing cells. The prophage-inducing effects that we observe apply broadly across different phage–bacteria systems and in complex communities. Finally, we identify bacteria that have colibactin resistance genes but lack colibactin biosynthetic genes. Many of these bacteria are infected with predicted prophages, and we show that the expression of their ClbS homologues provides immunity from colibactin-triggered induction. Our study reveals a mechanism by which colibactin production could affect microbiomes and highlights a role for microbial natural products in influencing population-level events such as phage outbreaks. The bacterial genotoxin colibactin triggers prophage-mediated lysis of neighbouring bacteria, a finding that provides insight into the dynamics of microbial communities and relationships between bacterial metabolite production and phage behaviour.
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影响因子：
56.9
作者：
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DOI：
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发表时间：
2012-10-05
期刊：
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影响因子：
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