Departamento de Medicina Preventiva Animal, Universidad de Chile, Santiago, Chile.
PLoS One. 2010 Feb 24;5(2):e9394. doi: 10.1371/journal.pone.0009394.
A bioinformatics comparison of Salmonella Pathogenicity Island 3 sequences from S. Typhi and S. Typhimurium serovars showed that ten genes are highly conserved. However three of them are pseudogenes in S. Typhi. Our aim was to understand what functions are lost in S. Typhi due to pseudogenes by constructing a S. Typhi genetic hybrid carrying the SPI-3 region of S. Typhimurium instead of its own SPI-3. We observed that under stressful conditions the hybrid strain showed a clear impairment in resistance to hydrogen peroxide and decreased survival within U937 culture monocytes. We hypothesized that the marT-fidL operon, encoded in SPI-3, was responsible for the new phenotypes because marT is a pseudogen in S. Typhi and has a demonstrated role as a transcriptional regulator in S. Typhimurium. Therefore we cloned and transferred the S. Typhimurium marT-fidL operon into S. Typhi and confirmed that invasion of monocytes was dramatically decreased. Finally, our findings suggest that the genomic and functional differences between SPI-3 sequences have implications in the host specificity of Typhi and Typhimurium serovars.
对伤寒沙门氏菌和鼠伤寒沙门氏菌血清型的沙门氏菌致病岛 3 序列的生物信息学比较表明,有 10 个基因高度保守。然而,其中 3 个基因在伤寒沙门氏菌中是假基因。我们的目的是通过构建携带鼠伤寒沙门氏菌 SPI-3 区域而不是其自身 SPI-3 的伤寒沙门氏菌遗传杂种,了解由于假基因而在伤寒沙门氏菌中丧失了哪些功能。我们观察到,在应激条件下,杂种菌株在抵抗过氧化氢方面明显受损,并且在 U937 培养单核细胞中的存活率降低。我们假设 SPI-3 中编码的 marT-fidL 操纵子是导致新表型的原因,因为 marT 在伤寒沙门氏菌中是一个假基因,并且在鼠伤寒沙门氏菌中作为转录调节剂具有明确的作用。因此,我们克隆并转移了鼠伤寒沙门氏菌的 marT-fidL 操纵子到伤寒沙门氏菌中,并证实单核细胞的侵袭明显减少。最后,我们的研究结果表明,SPI-3 序列的基因组和功能差异对伤寒和鼠伤寒血清型的宿主特异性具有影响。