Immuno-targeting of Staphylococcus aureus via surface remodeling complexes,Chemical Science

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Immuno-targeting of Staphylococcus aureus via surface remodeling complexes
Chemical Science ( IF 7.6 ) Pub Date : 2017-08-23 00:00:00 , DOI: 10.1039/c7sc02721d
Mary J. Sabulski _{1,

2,

3,

4} , Sean E. Pidgeon _{1,

2,

3,

4} , Marcos M. Pires _{1,

2,

3,

4}

Affiliation

Agents with novel mechanisms of action are needed to complement traditional antibiotics. Towards these goals, we have exploited the surface-homing properties of vancomycin to tag the surface of Gram-positive pathogens with immune cell attractants in two unique modes. First, vancomycin was conjugated to the small molecule hapten 2,4-dinitrophenol (DNP) to promote bacterial opsonization. Second, we built on these results by improving the tagging specificity and mechanism of incorporation by coupling it to a sortase A substrate peptide. We demonstrated, for the first time, that the surface of Staphylococcus aureus (S. aureus) can be metabolically labeled in live Caenorhabditis elegans hosts. These constructs represent a class of promising narrow-spectrum agents that target S. aureus for opsonization and establish a new surface labeling modality in live host organisms, which should be a powerful tool in dissecting features of host–pathogen interactions.

中文翻译：

通过表面重塑复合物对金黄色葡萄球菌的免疫靶向

需要具有新颖作用机制的药物来补充传统抗生素。为了实现这些目标，我们利用万古霉素的表面归巢特性，以两种独特的方式用免疫细胞引诱剂标记革兰氏阳性病原体的表面。首先，将万古霉素偶联至小分子半抗原2,4-二硝基苯酚（DNP），以促进细菌调理作用。其次，我们通过将标签特异性与分选酶A底物肽偶联来改善掺入的标签特异性和掺入机制，从而建立了这些结果。我们首次证明，金黄色葡萄球菌（金黄色葡萄球菌）的表面可以在活的秀丽隐杆线虫中进行代谢标记主机。这些构建体代表了一类有前途的窄谱因子，这些因子靶向金黄色葡萄球菌进行调理作用，并在活的宿主生物体中建立了新的表面标记方式，这应该是剖析宿主与病原体相互作用特征的有力工具。

更新日期：2017-09-25

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