Sporadic phage defense in epidemic Vibrio cholerae mediated by the toxin-antitoxin system DarTG is countered by a phage-encoded antitoxin mimic.
Sporadic phage defense in epidemic Vibrio cholerae mediated by the toxin-antitoxin system DarTG is countered by a phage-encoded antitoxin mimic.
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流行性霍乱弧菌中由毒素-抗毒素系统 DarTG 介导的零星噬菌体防御被噬菌体编码的抗毒素模拟物所抵消。
DOI：
10.1101/2023.12.14.571748
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Seed,KimberleyD
中科院分区：
文献类型：
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作者：
Patel,KishenM;Seed,KimberleyD
细菌和它们的病毒捕食者（噬菌体）不断进化，互相破坏。许多抑制噬菌体的细菌免疫系统是在可移动的遗传元件上编码的，这些遗传元件可以水平传播给不同的细菌。尽管免疫系统在细菌中普遍存在，但通常不知道这些免疫系统是否对宿主在自然界中遇到的噬菌体起作用。此外，证明这些噬菌体如何对抗这种免疫系统的例子有限。在这里，我们鉴定了全球致病菌霍乱弧菌的临床分离株，其中含有一种编码细菌免疫系统DarTG的新遗传元件，并揭示了免疫系统对共循环裂解噬菌体ICP1的影响。我们发现，DarTG抑制ICP1基因组复制，从而防止ICP1斑块。通过鉴定一种ICP1编码的蛋白，我们进一步表征了DarTG介导的防御和ICP1之间的冲突，该蛋白可以对抗DarTG并允许ICP1后代的产生。最后，我们确定这种蛋白AdfB是一种功能性抗毒素，可能通过直接相互作用来消除毒素DarT。随着DarTG系统在临床中的检测。我们观察到具有功能性抗毒素的ICP1分离株的增加。这些数据强调了监控的使用。霍乱及其裂解噬菌体，以了解自然界细菌及其噬菌体之间的共同进化军备竞赛。重要意义全球细菌性病原体霍乱弧菌每年造成约100万至400万霍乱病例。因此，研究影响其作为病原体持续存在的因素具有重要意义。其中一个影响是溶噬菌体ICP1，一旦被ICP1感染，V。choleraeis摧毁。到目前为止，我们已经观察到噬菌体ICP1形状v。霍乱通过抗噬菌体免疫系统的通量进化。在这里，我们探讨临床v。新的抗噬菌体免疫系统可以抑制ICP1，并发现毒素-抗毒素系统DarTG作为一种有效的抑制剂。我们的结果强调了v的重要性。霍乱和ICP1监测的新方法。面对ICP1，霍乱可以在人类宿主和水生水库中持续存在。
Bacteria and their viral predators (phages) are constantly evolving to subvert one another. Many bacterial immune systems that inhibit phages are encoded on mobile genetic elements that can be horizontally transmitted to diverse bacteria. Despite the pervasive appearance of immune systems in bacteria, it is not often known if these immune systems function against phages that the host encounters in nature. Additionally, there are limited examples demonstrating how these phages counter-adapt to such immune systems. Here, we identify clinical isolates of the global pathogenVibrio choleraeharboring a novel genetic element encoding the bacterial immune system DarTG and reveal the immune system’s impact on the co-circulating lytic phage ICP1. We show that DarTG inhibits ICP1 genome replication, thus preventing ICP1 plaquing. We further characterize the conflict between DarTG-mediated defense and ICP1 by identifying an ICP1-encoded protein that counters DarTG and allows ICP1 progeny production. Finally, we identify this protein, AdfB, as a functional antitoxin that abrogates the toxin DarT likely through direct interactions. Following the detection of the DarTG system in clinicalV. choleraeisolates, we observed a rise in ICP1 isolates with the functional antitoxin. These data highlight the use of surveillance ofV. choleraeand its lytic phages to understand the co-evolutionary arms race between bacteria and their phages in nature.IMPORTANCEThe global bacterial pathogenVibrio choleraecauses an estimated 1 to 4 million cases of cholera each year. Thus, studying the factors that influence its persistence as a pathogen is of great importance. One such influence is the lytic phage ICP1, as once infected by ICP1,V. choleraeis destroyed. To date, we have observed that the phage ICP1 shapesV. choleraeevolution through the flux of anti-phage bacterial immune systems. Here, we probe clinicalV. choleraeisolates for novel anti-phage immune systems that can inhibit ICP1 and discover the toxin-antitoxin system DarTG as a potent inhibitor. Our results underscore the importance ofV. choleraeand ICP1 surveillance to elaborate novel means by whichV. choleraecan persist in both the human host and aquatic reservoir in the face of ICP1.