Deciphering Active Prophages from Metagenomes.

Deciphering Active Prophages from Metagenomes.
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DOI:
10.1128/msystems.00084-22
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发表时间:
2022-04-26
期刊:
影响因子:
6.4
通讯作者:
--
中科院分区:
生物学2区
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温性噬菌体(原噬菌体)在自然界中普遍存在,并且在激活和裂解宿主(裂解阶段)之前作为宿主细胞的休眠组分(溶原阶段)持续存在。积极复制的前噬菌体有助于核心群落过程,例如实现细菌毒力、操纵生物地球化学循环以及推动微生物群落多样化。测序技术的最新进展已经允许鉴定和表征不同的噬菌体,但目前还不存在用于鉴定原噬菌体是否已活化的方法。在这里,我们提出了一种自动化的软件工具,用于估计前噬菌体是否处于感染的裂解或溶原性阶段。ESTAtE使用原噬菌体与宿主读段覆盖率的统计分析来破译活跃复制的原噬菌体,而不管原噬菌体是被诱导还是自发激活。我们证明,无论测序深度如何,ESTATE都是快速、准确和灵敏的。将ESTAtE应用于来自人肠道、鼠肠道和土壤环境的348个复杂宏基因组的前噬菌体,鉴定了不同的空间和时间前噬菌体活化特征,其中在鼠肠道样品中活性前噬菌体的比例最高。在接受抗生素治疗的婴儿或未接受治疗的婴儿中,我们确定了与特定治疗组相关的活性原噬菌体群体。在人类肠道的时间序列样本中,11个原噬菌体群体,一些编码硫代谢基因cysH或rhuM样毒力因子,随着时间的推移一直存在,但不活跃。总的来说,通过将原噬菌体与它们在自然界中塑造微生物群落的积极作用联系起来,ESTAtE将促进微生物组中病毒的准确表达。感染细菌的病毒是微生物组和生态系统的关键组成部分。它们可以杀死和操纵微生物,驱动行星尺度的过程和生物地球化学循环,并影响整个食物网络的结构。前病毒是在激活之前可以在其宿主的基因组中以休眠状态存在的病毒(溶原性阶段),以便复制和杀死宿主(裂解阶段)。最近的进展已经允许在自然界中识别不同的病毒,但没有方法存在用于表征原噬菌体及其感染阶段(原噬菌体活性)。我们开发和基准测试的自动化方法,MATERATE,从基因组数据中识别感染的阶段。我们提供的证据表明,活跃的原噬菌体在不同的环境和规模的身份和丰度。我们的方法将能够对微生物组和生态系统中的病毒进行准确和公正的分析。
Temperate phages (prophages) are ubiquitous in nature and persist as dormant components of host cells (lysogenic stage) before activating and lysing the host (lytic stage). Actively replicating prophages contribute to central community processes, such as enabling bacterial virulence, manipulating biogeochemical cycling, and driving microbial community diversification. Recent advances in sequencing technology have allowed for the identification and characterization of diverse phages, yet no approaches currently exist for identifying if a prophage has activated. Here, we present PropagAtE (Prophage Activity Estimator), an automated software tool for estimating if a prophage is in the lytic or lysogenic stage of infection. PropagAtE uses statistical analyses of prophage-to-host read coverage ratios to decipher actively replicating prophages, irrespective of whether prophages were induced or spontaneously activated. We demonstrate that PropagAtE is fast, accurate, and sensitive, regardless of sequencing depth. Application of PropagAtE to prophages from 348 complex metagenomes from human gut, murine gut, and soil environments identified distinct spatial and temporal prophage activation signatures, with the highest proportion of active prophages in murine gut samples. In infants treated with antibiotics or infants without treatment, we identified active prophage populations correlated with specific treatment groups. Within time series samples from the human gut, 11 prophage populations, some encoding the sulfur metabolism gene cysH or a rhuM-like virulence factor, were consistently present over time but not active. Overall, PropagAtE will facilitate accurate representations of viruses in microbiomes by associating prophages with their active roles in shaping microbial communities in nature. IMPORTANCE Viruses that infect bacteria are key components of microbiomes and ecosystems. They can kill and manipulate microorganisms, drive planetary-scale processes and biogeochemical cycling, and influence the structures of entire food networks. Prophages are viruses that can exist in a dormant state within the genome of their host (lysogenic stage) before activating in order to replicate and kill the host (lytic stage). Recent advances have allowed for the identification of diverse viruses in nature, but no approaches exist for characterizing prophages and their stages of infection (prophage activity). We develop and benchmark an automated approach, PropagAtE, to identify the stages of infection of prophages from genomic data. We provide evidence that active prophages vary in identity and abundance across multiple environments and scales. Our approach will enable accurate and unbiased analyses of viruses in microbiomes and ecosystems.
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