Division of Vector-Borne Infectious Diseases, Bacterial Diseases Branch, Centers for Disease Control and Prevention, Foothills Campus, Fort Collins, Colorado 80521, USA.
Vector Borne Zoonotic Dis. 2010 Jan-Feb;10(1):85-92. doi: 10.1089/vbz.2009.0043.
Despite the widespread presence of bubonic plague in sylvatic reservoirs throughout the world, the causative agent (Yersinia pestis) evolved in its present form within the last 20,000 years from enteropathogenic Yersinia pseudotuberculosis. Comparison of the genomes from the two species revealed that Y. pestis possesses only a few unique plasmid-encoded genes that contribute to acute disease, whereas this organism has lost about 13% of the chromosomal genes that remain active in Y. pseudotuberculosis. These losses reflect readily detectable additions, deletions, transpositions, inversions, and acquisition of about 70 insertion sequence (IS) inserts, none of which are likely to promote increased virulence. In contrast, major enzymes of intermediary metabolism, including glucose 6-phosphate dehydrogenase (Zwf ) and aspartase, are present but not catalytically functional due to the presence of missense mutations. The latter are generally not detectable by the technology of bioinformatics and, in the case of Y. pestis, result in radical changes in the metabolic flow of carbon. As an important consequence, plague bacilli exhibit a stringent low-calcium response characterized by conversion of L-glutamate (and metabolically related amino acids) to L-aspartate with secretion of the latter into supernatant fluid at 37 degrees C in culture media containing Na(+) but lacking added Ca(2+). This phenomenon also occurs in vivo and likely adversely affects the bioenergetics of host amino acid pools. Curiously, aspartase is functional in all tested enzootic (pestoides) strains of Y. pestis. These isolates are typically restricted to the ancient plague reservoirs of Central Asia and Africa and are fully virulent in members of the rodent Superfamily Muroidea but avirulent in guinea pigs and man. The implications of these findings for the distribution and ecology of Y. pestis could be significant.
尽管在世界范围内的森林生态系统中普遍存在鼠疫，但病原体（鼠疫耶尔森菌）是在过去的 2 万年内从肠致病性假结核耶尔森菌进化而来的。对这两个物种的基因组进行比较发现，鼠疫耶尔森菌只拥有少数几个独特的质粒编码基因，这些基因有助于引起急性疾病，而这种生物体失去了约 13%在假结核耶尔森菌中仍活跃的染色体基因。这些缺失反映了易于检测的添加、缺失、转位、倒位和大约 70 个插入序列（IS）插入的获得，其中没有一个可能促进毒力增加。相比之下，包括葡萄糖 6-磷酸脱氢酶（Zwf）和天冬氨酸酶在内的中间代谢主要酶都存在，但由于存在错义突变而没有催化功能。后者通常不能通过生物信息学技术检测到，而在鼠疫耶尔森菌的情况下，会导致碳代谢流的根本性变化。作为一个重要的结果，鼠疫杆菌表现出严格的低钙反应，其特征是在含有 Na+但缺乏添加 Ca2+的培养基中，L-谷氨酸（和代谢相关的氨基酸）转化为 L-天冬氨酸，并将后者分泌到上清液中，温度为 37 摄氏度。这种现象也发生在体内，可能对宿主氨基酸池的生物能量学产生不利影响。奇怪的是，天冬氨酸酶在所有测试的鼠疫耶尔森菌地方病（pestoides）菌株中都具有功能。这些分离株通常局限于中亚和非洲的古老鼠疫储库，对啮齿目动物超级家族的成员具有完全的毒力，但对豚鼠和人类没有毒力。这些发现对鼠疫耶尔森菌的分布和生态学可能具有重要意义。
