在哺乳动物细胞和组织中发现具有复制能力的环状 DNA 分子与多种衰弱性疾病有关，例如多发性硬化症 (MS)、牛海绵状脑病 (BSE) 和结直肠癌 (CRC)。这些环状 DNA 分子，也称为牛肉和奶因子 (BMMF) 和可变 (X) 潜伏期的缓慢进行性隐性感染 (SPHINX)，与鲍曼不动杆菌菌株的质粒具有显着 (80%) 的序列相似性。纳米结构，如细菌外膜囊泡 (OMV)，可作为运输生物分子货物的载体，并有可能促进 DNA 的跨界横向流动。本研究证实，源自鲍曼不动杆菌 DS002 的 OMV 携带噬菌体 AbDs1 的四个质粒和基因组 (pTS236)，在注射异硫氰酸荧光素后，成功到达身体的不同部位，包括中枢神经系统，这强化了所提出的假设。将 FITC）标记的 OMV 注入实验小鼠体内。在四种 OMV 相关质粒中，在内腔内鉴定出三种（pTS4586、pTS9900 和 pTS134338），第四种（pTS11291）在 OMV 表面发现。除了固有质粒之外，噬菌体编码的蛋白 Orf96 通过与 OMV 相关孔蛋白 OmpA 建立强相互作用而锚定在 OMV 表面。有趣的是，当与 Neuro2A 细胞一起孵育时，标记的 OMV 的一个子集会跨膜移位并到达细胞的细胞质空间。总的来说，本文提出的实验证据强调了 OMV 作为将含有质粒和噬菌体基因组的分子货物递送到不同哺乳动物组织和细胞的载体的巨大潜力。几项独立研究已经证明，细菌和病毒来源的具有复制能力的环状 DNA 分子的存在。哺乳动物细胞和组织。然而，关于它们的起源和哺乳动物细胞的横向迁移性的研究很少。我们的工作描述了环状 DNA 的存在，类似于哺乳动物细胞中鉴定的 DNA 分子，OMV 源自鲍曼不动杆菌 DS002 的土壤分离株。此外，这项工作还提供了视觉证据，证明在将 OMV 静脉注射到实验小鼠体内后数小时内，标记的 OMV 即可到达实验小鼠的不同器官。一些标记的 OMV 甚至穿过 Neuro2A 的膜，表明细菌和哺乳动物之间存在王国间水平流动。

The discovery of Replication Competent Circular DNA molecules in mammalian cells and tissues is being linked to debilitating diseases, such as multiple sclerosis (MS), bovine spongiform encephalopathy (BSE), and colorectal cancer (CRC). These circular DNA molecules, otherwise known as bovine meat and milk factors (BMMFs) and Slow Progressive Hidden INfections of variable (X) latency (SPHINX), bear significant (80%) sequence similarity with the plasmids of Acinetobacter baumannii strains. Nanostructures, such as bacterial outer membrane vesicles (OMVs) serve as vehicles for transporting biomolecular cargo and have the potential to facilitate interkingdom lateral mobility of DNA. Strengthening the proposed hypothesis, this study demonstrates that OMVs derived from A. baumannii DS002 carrying four plasmids and genome (pTS236) of phage, AbDs1, successfully reached different parts of the body, including the central nervous system, following the injection of fluorescein isothiocyanate (FITC)-labeled OMVs into experimental mice. Out of the four OMV-associated plasmids, three (pTS4586, pTS9900, and pTS134338) were identified within the lumen, and the fourth one (pTS11291) was found on the surface of OMVs. In addition to the indigenous plasmids, the phage-encoded protein, Orf96, anchored on the surface of the OMVs by establishing a strong interaction with the OMV-associated porin, OmpA. Intriguingly, a subset of labeled OMVs, when incubated with Neuro2A cells, translocated across the membrane and reached to the cytoplasmic space of the cells. Collectively, the experimental evidence presented herein underscores the promising potential of OMVs as vehicles for delivering molecular cargo containing plasmids and phage genomes to diverse mammalian tissues and cells.Several independent studies have demonstrated the existence of replication competent circular DNA molecules of bacterial and viral origin in mammalian cells and tissues. However, studies about their origin and lateral mobility to mammalian cells are scarce. Our work describes the existence of circular DNA, similar to that of DNA molecules identified in mammalian cells, OMVs derived from soil isolate of A. baumannii DS002. Furthermore, the work also provides visual evidence that demonstrates the passage of labeled OMVs to different organs of experimental mice within hours after intravenously administering OMVs into experimental mice. Some of the labeled OMVs have even crossed the membrane of Neuro2A, suggesting the existence of interkingdom horizontal mobility between bacteria and mammals.