Run-off replication of host-adaptability genes is associated with gene transfer agents in the genome of mouse-infecting Bartonella grahamii.

Run-off replication of host-adaptability genes is associated with gene transfer agents in the genome of mouse-infecting Bartonella grahamii.
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宿主适应性基因的径流复制与小鼠感染Bartonella grahamii基因组中的基因转移剂有关。

DOI:
10.1371/journal.pgen.1000546
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发表时间:
2009-07
期刊:
影响因子:
4.5
通讯作者:
Andersson SG
Andersson SG
中科院分区:
生物学2区
文献类型:
--
作者:
Berglund EC;Frank AC;Calteau A;Vinnere Pettersson O;Granberg F;Eriksson AS;Näslund K;Holmberg M;Lindroos H;Andersson SG

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巴尔通体属包括适应哺乳动物的兼性细胞内细菌,包括先前认识的和新出现的人类病原体。我们报告了 grahamii 巴尔通体的 2,341,328 bp 基因组序列,它是野生啮齿动物中最常见的巴尔通体物种之一。比较基因组学表明,与啮齿动物相关的巴尔通体物种比相关的人类特异性病原体具有更高的推定宿主适应性因素基因拷贝数。许多这些基因簇位于 461 kb 的高度动态区域。通过与为 B. grahamii 基因组设计的微阵列杂交,我们观察到该区域存在大量的、推定为噬菌体衍生的径流复制。我们还发现了一种新型基因转移剂,它将细菌基因组包装成 14 kb 片段,并过度表达扩增的 DNA。这是首次将径流复制产物与基因转移剂联系起来。由于扩增区域中宿主适应蛋白的基因簇浓度很高,并且编码基因转移剂的基因和噬菌体起源在巴尔通体中得到很好的保守,因此我们假设这些系统是由选择驱动的。我们提出,径流复制与基因转移剂的结合促进了宿主适应性因子的多样化和快速传播,从而促进了巴尔通体的宿主转移。 新出现的传染病代表了日益严重的人类健康问题,许多疾病爆发的例子是由动物传播给人类引起的,例如最近的禽流感病毒。涉及毒力和抗生素耐药性的基因通常由质粒和病毒等移动元件携带,它们以惊人的速度介导细胞之间的转移。啮齿动物是传染源的主要携带者,因此研究以啮齿动物作为天然宿主宿主的细菌的基因转移过程尤为重要。我们研究了一种自然适应小鼠的细菌的基因组,并鉴定出比之前已知的人类病原体中观察到的更多的假定宿主相互作用基因。此外,这些基因大多数位于基因组约25%的片段中,该片段被大规模扩增并包装成病毒颗粒。这是将细菌染色体的一部分定向包装成病毒颗粒的首次演示,我们认为这是增加感染过程中涉及的基因交换的新策略。
The genus Bartonella comprises facultative intracellular bacteria adapted to mammals, including previously recognized and emerging human pathogens. We report the 2,341,328 bp genome sequence of Bartonella grahamii, one of the most prevalent Bartonella species in wild rodents. Comparative genomics revealed that rodent-associated Bartonella species have higher copy numbers of genes for putative host-adaptability factors than the related human-specific pathogens. Many of these gene clusters are located in a highly dynamic region of 461 kb. Using hybridization to a microarray designed for the B. grahamii genome, we observed a massive, putatively phage-derived run-off replication of this region. We also identified a novel gene transfer agent, which packages the bacterial genome, with an over-representation of the amplified DNA, in 14 kb pieces. This is the first observation associating the products of run-off replication with a gene transfer agent. Because of the high concentration of gene clusters for host-adaptation proteins in the amplified region, and since the genes encoding the gene transfer agent and the phage origin are well conserved in Bartonella, we hypothesize that these systems are driven by selection. We propose that the coupling of run-off replication with gene transfer agents promotes diversification and rapid spread of host-adaptability factors, facilitating host shifts in Bartonella. Emerging infectious diseases represent an increasing human health problem with many examples of disease outbreaks caused by transmissions from animals to humans, such as, most recently, the bird flu virus. Genes involved in virulence and antibiotic resistance are often carried by mobile elements like plasmids and viruses, which mediate transfer between cells at an amazing speed. Rodents represent a major carrier of infectious agents, and it is therefore particularly important to study the gene transfer processes in bacteria that use rodents as their natural host reservoir. We have studied the genome of a bacterium that is naturally adapted to mice and identified many more putative host-interaction genes than were observed in previously recognized human pathogens. Furthermore, most of these genes are located in a segment of about 25% of the genome, which was massively amplified and packaged into viral particles. This is the first demonstration of targeted packaging of a portion of the bacterial chromosome into viral particles, and we propose that this is a novel strategy for increased exchange of genes involved in the infectious process.
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