Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
Infect Immun. 2012 Oct;80(10):3693-705. doi: 10.1128/IAI.00529-12. Epub 2012 Jul 16.
Yersinia pestis, the causative agent of plague, evolved from the gastrointestinal pathogen Yersinia pseudotuberculosis. Both species have numerous type Va autotransporters, most of which appear to be highly conserved. In Y. pestis CO92, the autotransporter genes yapK and yapJ share a high level of sequence identity. By comparing yapK and yapJ to three homologous genes in Y. pseudotuberculosis IP32953 (YPTB0365, YPTB3285, and YPTB3286), we show that yapK is conserved in Y. pseudotuberculosis, while yapJ is unique to Y. pestis. All of these autotransporters exhibit >96% identity in the C terminus of the protein and identities ranging from 58 to 72% in their N termini. By extending this analysis to include homologous sequences from numerous Y. pestis and Y. pseudotuberculosis strains, we determined that these autotransporters cluster into a YapK (YPTB3285) class and a YapJ (YPTB3286) class. The YPTB3286-like gene of most Y. pestis strains appears to be inactivated, perhaps in favor of maintaining yapJ. Since autotransporters are important for virulence in many bacterial pathogens, including Y. pestis, any change in autotransporter content should be considered for its impact on virulence. Using established mouse models of Y. pestis infection, we demonstrated that despite the high level of sequence identity, yapK is distinct from yapJ in its contribution to disseminated Y. pestis infection. In addition, a mutant lacking both of these genes exhibits an additive attenuation, suggesting nonredundant roles for yapJ and yapK in systemic Y. pestis infection. However, the deletion of the homologous genes in Y. pseudotuberculosis does not seem to impact the virulence of this organism in orogastric or systemic infection models.
鼠疫耶尔森菌是鼠疫的病原体,它是从胃肠道病原体假结核耶尔森菌进化而来的。这两个物种都有许多类型 Va 自转运蛋白,其中大多数似乎高度保守。在 Y. pestis CO92 中,自转运基因 yapK 和 yapJ 具有高度的序列同一性。通过将 yapK 和 yapJ 与假结核耶尔森菌 IP32953 中的三个同源基因(YPTB0365、YPTB3285 和 YPTB3286)进行比较,我们表明 yapK 在假结核耶尔森菌中是保守的,而 yapJ 是 Y. pestis 的特有基因。所有这些自转运蛋白在蛋白质的 C 端具有 >96%的同一性,在 N 端具有 58%至 72%的同一性。通过将这种分析扩展到包括来自许多 Y. pestis 和 Y. pseudotuberculosis 菌株的同源序列,我们确定这些自转运蛋白聚类为 yapK(YPTB3285)类和 yapJ(YPTB3286)类。大多数 Y. pestis 菌株的 YPTB3286 样基因似乎失活,可能有利于维持 yapJ。由于自转运蛋白在许多细菌病原体(包括鼠疫耶尔森菌)的毒力中很重要,因此应该考虑自转运蛋白含量的任何变化对毒力的影响。使用已建立的鼠疫耶尔森菌感染小鼠模型,我们证明尽管序列同一性很高,但 yapK 在其对播散性鼠疫耶尔森菌感染的贡献方面与 yapJ 不同。此外,缺失这两个基因的突变体表现出附加衰减,表明 yapJ 和 yapK 在系统性鼠疫耶尔森菌感染中具有非冗余作用。然而,假结核耶尔森菌同源基因的缺失似乎不会影响该生物体在经口或全身感染模型中的毒力。