Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA.
Mol Microbiol. 2013 Jul;89(2):276-87. doi: 10.1111/mmi.12273. Epub 2013 Jun 10.
Autotransporters, the largest family of secreted proteins in Gram-negative bacteria, perform a variety of functions, including adherence, cytotoxicity and immune evasion. In Yersinia pestis the autotransporter YapE has adhesive properties and contributes to disease in the mouse model of bubonic plague. Here, we demonstrate that omptin cleavage of Y. pestis YapE is required to mediate bacterial aggregation and adherence to eukaryotic cells. We demonstrate that omptin cleavage is specific for the Y. pestis and Y. pseudotuberculosis YapE orthologues but is not conserved in the Yersinia enterocolitica protein. We also show that cleavage of YapE occurs in Y. pestis but not in the enteric Yersinia species, and requires the omptin Pla (plasminogen activator protease), which is encoded on the Y. pestis-specific plasmid pPCP1. Together, these data show that post-translation modification of YapE appears to be specific to Y. pestis, was acquired along with the acquisition of pPCP1 during the divergence of Y. pestis from Y. pseudotuberculosis, and are the first evidence of a novel mechanism to regulate bacterial adherence.
自动转运蛋白是革兰氏阴性菌中最大的分泌蛋白家族,具有多种功能,包括粘附、细胞毒性和免疫逃逸。在鼠疫耶尔森氏菌中,自动转运蛋白 yapE 具有粘附特性,并有助于在鼠疫杆菌的 bubonic plague 小鼠模型中发病。在这里,我们证明 omptin 对 yapE 的切割是介导细菌聚集和粘附真核细胞所必需的。我们证明 omptin 切割是 yapE 的特异性,无论是鼠疫耶尔森氏菌还是假结核耶尔森氏菌的 yapE 同源物,但在肠耶尔森氏菌蛋白中并不保守。我们还表明 yapE 的切割发生在鼠疫耶尔森氏菌中,但不在肠道耶尔森氏菌中,并且需要 omptin Pla(纤溶酶原激活蛋白酶),它编码在鼠疫耶尔森氏菌特异性质粒 pPCP1 上。总之,这些数据表明 yapE 的翻译后修饰似乎是鼠疫耶尔森氏菌特有的,是在鼠疫耶尔森氏菌从假结核耶尔森氏菌分化过程中与 pPCP1 的获得一起获得的,并且是调节细菌粘附的新机制的第一个证据。