Langridge Gemma C, Fookes Maria, Connor Thomas R, Feltwell Theresa, Feasey Nicholas, Parsons Bryony N, Seth-Smith Helena M B, Barquist Lars, Stedman Anna, Humphrey Tom, Wigley Paul, Peters Sarah E, Maskell Duncan J, Corander Jukka, Chabalgoity Jose A, Barrow Paul, Parkhill Julian, Dougan Gordon, Thomson Nicholas R
Pathogen Genomics, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom;
Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, United Kingdom; Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, United Kingdom;
Proc Natl Acad Sci U S A. 2015 Jan 20;112(3):863-8. doi: 10.1073/pnas.1416707112. Epub 2014 Dec 22.
Many bacterial pathogens are specialized, infecting one or few hosts, and this is often associated with more acute disease presentation. Specific genomes show markers of this specialization, which often reflect a balance between gene acquisition and functional gene loss. Within Salmonella enterica subspecies enterica, a single lineage exists that includes human and animal pathogens adapted to cause infection in different hosts, including S. enterica serovar Enteritidis (multiple hosts), S. Gallinarum (birds), and S. Dublin (cattle). This provides an excellent evolutionary context in which differences between these pathogen genomes can be related to host range. Genome sequences were obtained from ∼ 60 isolates selected to represent the known diversity of this lineage. Examination and comparison of the clades within the phylogeny of this lineage revealed signs of host restriction as well as evolutionary events that mark a path to host generalism. We have identified the nature and order of events for both evolutionary trajectories. The impact of functional gene loss was predicted based upon position within metabolic pathways and confirmed with phenotyping assays. The structure of S. Enteritidis is more complex than previously known, as a second clade of S. Enteritidis was revealed that is distinct from those commonly seen to cause disease in humans or animals, and that is more closely related to S. Gallinarum. Isolates from this second clade were tested in a chick model of infection and exhibited a reduced colonization phenotype, which we postulate represents an intermediate stage in pathogen-host adaptation.
许多细菌病原体具有特异性，感染一种或少数几种宿主，这通常与更急性的疾病表现相关。特定的基因组显示出这种特异性的标记，这往往反映了基因获得与功能性基因丢失之间的平衡。在肠炎沙门氏菌肠炎亚种中，存在一个单一的谱系，其中包括适应于在不同宿主中引起感染的人类和动物病原体，包括肠炎沙门氏菌肠炎血清型（多种宿主）、鸡沙门氏菌（鸟类）和都柏林沙门氏菌（牛）。这提供了一个绝佳的进化背景，在此背景下，这些病原体基因组之间的差异可以与宿主范围相关联。从约60个分离株中获得了基因组序列，这些分离株被选择用来代表该谱系已知的多样性。对该谱系系统发育中的进化枝进行检查和比较，揭示了宿主限制的迹象以及标志着通向宿主泛化路径的进化事件。我们已经确定了这两条进化轨迹的事件性质和顺序。基于代谢途径中的位置预测了功能性基因丢失的影响，并通过表型分析进行了证实。肠炎沙门氏菌的结构比以前所知的更为复杂，因为发现了肠炎沙门氏菌的第二个进化枝，它与通常在人类或动物中引起疾病的进化枝不同，并且与鸡沙门氏菌的关系更为密切。对来自这个第二个进化枝的分离株在雏鸡感染模型中进行了测试，它们表现出定植表型降低的情况，我们推测这代表了病原体-宿主适应的一个中间阶段。
