D-Amino Acid Mediated Recruitment of Endogenous Antibodies to Bacterial Surfaces

D-Amino Acid Mediated Recruitment of Endogenous Antibodies to Bacterial Surfaces
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DOI:
10.1021/cb5002685
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发表时间:
2014-07-01
影响因子:
4
通讯作者:
Pires, Marcos M.
Pires, Marcos M.
中科院分区:
生物学2区
文献类型:
--
作者:
Fura, Jonathan M.;Sabulski, Mary J.;Pires, Marcos M.

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在过去的几十年中,抗生素耐药性细菌菌株的数量一直在不断增加。对抗细菌的非传统途径可能为该领域药物发现的持续问题提供有吸引力的替代方案。在此,我们描述了细菌D-氨基酸抗体募集治疗(DART)的发展的初步框架。DART代表了一种有前途的抗生素策略,它利用细菌的混杂性来掺入非天然的D-氨基酸,随后将抗体募集到细菌表面。2,4-二硝基苯基(DNP)与各种D-氨基酸的缀合导致发现了特异性标记枯草芽孢杆菌和金黄色葡萄球菌表面的D-氨基酸,用于募集抗DNP抗体(人血清中高度丰富的抗体)。该系统代表了一种新的策略,作为一种抗菌治疗的目标是嗜热革兰氏阳性菌。
The number of antibiotic resistant bacterial strains has been continuously increasing over the last few decades. Nontraditional routes to combat bacteria may offer an attractive alternative to the ongoing problem of drug discovery in this field. Herein, we describe the initial framework toward the development of bacterial D-amino acid antibody recruitment therapy (DART). DART represents a promising antibiotic strategy by exploiting the promiscuity of bacteria to incorporate unnatural D-amino acids and subsequently recruit antibodies to the bacterial surface. The conjugation of 2,4-dinitrophenyl (DNP) to various D-amino acids led to the discovery of a D-amino acid that specifically tags the surface of Bacillus subtilis and Staphylococcus aureus for the recruitment of anti-DNP antibodies (a highly abundant antibody in human serum). This system represents a novel strategy as an antibacterial therapy that targets planktonic Gram-positive bacteria.