Patterns of Genome Evolution That Have Accompanied Host Adaptation in Salmonella Pullorum. Salmonella enterica subsp. enterica serovar Pullorum strain:S44987

Many bacterial pathogens are specialised, infecting only one, or a few, hosts, and this is often associated with more acute disease presentation. By looking at specific genomes we can see markers of this specialisation, 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 and S. Pullorum (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. In the host adapted clades, loss of particular traits such as tetrathionate reduction and adenosylcobalamin biosynthesis could be related to their role in host infection. 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 which are more closely related to S. Gallinarum. Isolates from this novel clade were tested in a chick model of infection, and exhibited a reduced colonisation phenotype, which we postulate represents an intermediate stage in pathogen-host adaptation.

诸多细菌性病原均具有宿主专一性，仅感染单一或少数几种宿主，且此类病原往往引发更为急性的疾病表型。通过分析特定基因组，可识别此类专一性的分子标记，这些标记通常反映了基因获取与功能基因丢失之间的平衡。肠炎沙门氏菌肠炎亚种（Salmonella enterica subspecies enterica）内存在一个单一演化谱系，该谱系涵盖适应不同宿主的人类与动物病原，包括肠炎沙门氏菌血清型肠炎（S. enterica serovar Enteritidis，多宿主）、鸡沙门氏菌（S. Gallinarum）与鸡白痢沙门氏菌（S. Pullorum，均感染禽类）以及都柏林沙门氏菌（S. Dublin，感染牛）。该谱系为研究病原基因组差异与宿主范围的关联提供了绝佳的进化研究背景。研究人员针对该谱系的已知多样性筛选了约60株分离菌，获取了其全基因组序列。对该谱系系统发育树（phylogeny）内各演化支（clade）的分析与比较，揭示了宿主限制的相关特征，以及指向宿主泛化的进化事件。本研究明确了两种进化路径对应的事件本质与发生顺序。研究人员基于基因在代谢通路中的位置预测了功能基因丢失的影响，并通过表型分析实验（phenotyping assays）进行了验证。在宿主适应性演化支中，特定性状（如四硫磺酸还原（tetrathionate reduction）与腺苷钴胺素生物合成（adenosylcobalamin biosynthesis））的丢失可能与其在宿主感染过程中的功能相关。肠炎沙门氏菌的系统发育结构较此前认知更为复杂：研究发现了一类全新的肠炎沙门氏菌演化支，该支系与通常引发人类或动物疾病的常见肠炎沙门氏菌菌株存在显著差异，且与鸡沙门氏菌（S. Gallinarum）的亲缘关系更为紧密。研究人员利用鸡感染模型对该新型演化支的分离菌进行了测试，结果显示其定殖表型有所减弱，我们推测这代表了病原-宿主协同进化过程中的中间过渡阶段。