Protective activity of the CnaBE3 domain conserved among Staphylococcus aureus Sdr proteins.
Protective activity of the CnaBE3 domain conserved among Staphylococcus aureus Sdr proteins.
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DOI：
10.1371/journal.pone.0074718
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Manetti AG
中科院分区：
文献类型：
--
作者：
Becherelli M;Prachi P;Viciani E;Biagini M;Fiaschi L;Chiarot E;Nosari S;Brettoni C;Marchi S;Biancucci M;Fontana MR;Montagnani F;Bagnoli F;Barocchi MA;Manetti AG
金黄色葡萄球菌是一种机会致病菌，与人类皮肤和鼻孔共生，但也是侵袭性医院感染和社区获得性感染的罪魁祸首。金黄色葡萄球菌通过表面粘附素，如SDRC、SdrD和SdrE蛋白等与宿主组织黏附。SDR蛋白家族连同一个功能性的A结构域，分别包含两个、三个或五个称为B基序的重复序列，这些重复序列组成了Cna B结构域。据报道，SdrD和SdrE蛋白在动物模型中对金黄色葡萄球菌临床分离株的侵袭性疾病或致命性攻击具有保护作用。在这项研究中，我们鉴定了一个126个氨基酸的序列，包含一个Cna B结构域，在三个SDR蛋白中保守。这三个片段被定义为Cna BC2、D5和E3结构域，尽管它们在系统发育上属于不同的菌株，但显示出很高的序列相似性。基于序列保守数据，我们选择了Cna BE3结构域进行进一步的分析和鉴定。针对重组Cna BE3结构域的多克隆抗体可识别金黄色葡萄球菌不同谱系的SdrE、SDRC和SdrD蛋白。此外，我们还证明了在金黄色葡萄球菌感染的过程中，Cna BE3结构域在体内得到了表达，单独免疫该结构域可以显著降低金黄色葡萄球菌攻击小鼠的细菌负荷。此外，我们还表明，接种Cna BE3疫苗后细菌的减少是由于功能性抗体的作用。最后，我们证明了含有Cna BE3结构域的SdrE蛋白区域对胰酶消化具有抵抗力，这一特征通常与异肽键的存在有关。
Staphylococcus aureus is an opportunistic pathogen, commensal of the human skin and nares, but also responsible for invasive nosocomial as well as community acquired infections. Staphylococcus aureus adheres to the host tissues by means of surface adhesins, such as SdrC, SdrD, and SdrE proteins. The Sdr family of proteins together with a functional A domain, contain respectively two, three or five repeated sequences called B motifs which comprise the CnaB domains. SdrD and SdrE proteins were reported to be protective in animal models against invasive diseases or lethal challenge with human clinical S. aureus isolates. In this study we identified a 126 amino acid sequence containing a CnaB domain, conserved among the three Sdr proteins. The three fragments defined here as CnaBC2, D5 and E3 domains even though belonging to phylogenetically distinct strains, displayed high sequence similarity. Based on the sequence conservation data, we selected the CnaBE3 domain for further analysis and characterization. Polyclonal antibodies raised against the recombinant CnaBE3 domain recognized SdrE, SdrC and SdrD proteins of different S. aureus lineages. Moreover, we demonstrated that the CnaBE3 domain was expressed in vivo during S. aureus infections, and that immunization of this domain alone significantly reduces the bacterial load in mice challenged with S. aureus. Furthermore, we show that the reduction of bacteria by CnaBE3 vaccination is due to functional antibodies. Finally, we demonstrated that the region of the SdrE protein containing the CnaBE3 domain was resistant to trypsin digestion, a characteristic often associated with the presence of an isopeptide bond.
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影响因子：
4.2
作者：
Corrigan, Rebecca M.;Miajlovic, Helen;Foster, Timothy J.
通讯作者：
Foster, Timothy J.
影响因子：
14.9
作者：
Goujon M;McWilliam H;Li W;Valentin F;Squizzato S;Paern J;Lopez R
通讯作者：
Lopez R
影响因子：
5.5
作者：
Kabanova, Anna;Margarit, Immaculada;Costantino, Paolo
通讯作者：
Costantino, Paolo
DOI：
10.1099/00221287-144-12-3387
发表时间：
1998-12-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
Josefsson, E;McCrea, KW;Foster, TJ
通讯作者：
Foster, TJ
β-系蛋白是金黄色葡萄球菌MSCRAMM SDRC的配体。
影响因子：
6.7
作者：
Barbu EM;Ganesh VK;Gurusiddappa S;Mackenzie RC;Foster TJ;Sudhof TC;Höök M
通讯作者：
Höök M