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当巨噬细胞感染时,黏附侵袭性大肠杆菌 LF82 中的噬菌体生产被阻断。

Phage production is blocked in the adherent-invasive Escherichia coli LF82 upon macrophage infection.

机构信息

Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France.

Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, Paris, France.

出版信息

PLoS Pathog. 2023 Feb 2;19(2):e1011127. doi: 10.1371/journal.ppat.1011127. eCollection 2023 Feb.

Abstract

Adherent-invasive Escherichia coli (AIEC) strains are frequently recovered from stools of patients with dysbiotic microbiota. They have remarkable properties of adherence to the intestinal epithelium, and survive better than other E. coli in macrophages. The best studied of these AIEC is probably strain LF82, which was isolated from a Crohn's disease patient. This strain contains five complete prophages, which have not been studied until now. We undertook their analysis, both in vitro and inside macrophages, and show that all of them form virions. The Gally prophage is by far the most active, generating spontaneously over 108 viral particles per mL of culture supernatants in vitro, more than 100-fold higher than the other phages. Gally is also over-induced after a genotoxic stress generated by ciprofloxacin and trimethoprim. However, upon macrophage infection, a genotoxic environment, this over-induction is not observed. Analysis of the transcriptome and key steps of its lytic cycle in macrophages suggests that the excision of the Gally prophage continues to be repressed in macrophages. We conclude that strain LF82 has evolved an efficient way to block the lytic cycle of its most active prophage upon macrophage infection, which may participate to its good survival in macrophages.

摘要

黏附侵袭型大肠杆菌(AIEC)菌株经常从肠道微生物失调的患者粪便中分离出来。它们具有显著的黏附肠上皮的特性,并且在巨噬细胞中比其他大肠杆菌更能存活。这些 AIEC 中研究最多的可能是 LF82 菌株,它是从克罗恩病患者中分离出来的。该菌株含有五个完整的噬菌体,这些噬菌体直到现在才被研究过。我们对它们进行了分析,包括在体外和巨噬细胞内的分析,并表明它们都能形成病毒粒子。Gally 噬菌体是迄今为止最活跃的噬菌体,在体外培养上清液中每毫升自发产生超过 108 个病毒粒子,比其他噬菌体高出 100 多倍。在环丙沙星和甲氧苄啶产生的遗传毒性应激后,Gally 也被过度诱导。然而,在巨噬细胞感染时,即遗传毒性环境下,这种过度诱导并没有被观察到。对其溶原周期的转录组和关键步骤进行分析表明,Gally 噬菌体的切除在巨噬细胞中继续受到抑制。我们得出结论,LF82 菌株在巨噬细胞感染时进化出了一种有效的方法来阻断其最活跃的噬菌体的溶原周期,这可能有助于其在巨噬细胞中的良好存活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/948b/9928086/301ab0f5daac/ppat.1011127.g001.jpg

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