Kaufmann Gunnar F, Sartorio Rafaella, Lee Sang-Hyeup, Mee Jenny M, Altobell Laurence J, Kujawa David P, Jeffries Emily, Clapham Bruce, Meijler Michael M, Janda Kim D
The Skaggs Institute for Chemical Biology and Departments of Chemistry and Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
J Am Chem Soc. 2006 Mar 8;128(9):2802-3. doi: 10.1021/ja0578698.
Many bacterial pathogens coordinate their virulence factor expression in a cell density-dependent manner. This population-dependent coordination of gene expression in bacteria has been termed "quorum sensing" (QS). N-Acyl homoserine lactones (AHLs) are used by over 70 Gram-negative bacterial species as autoinducers. Inhibition of QS signaling might represent a new target for antimicrobial therapy. Here we report the hapten design, synthesis, generation of monoclonal antibodies (mAbs) against AHLs, and the evaluation of these mAbs for their ability to blunt QS signaling and inhibit virulence factor expression in P. aeruginosa. The mAbs can be envisioned as a tool for future investigations into AHL-based QS, which may aid in gaining new insights into the pathogenesis of P. aeruginosa and may ultimately lead to the development of new strategies to combat bacterial diseases.
许多细菌病原体以细胞密度依赖的方式协调其毒力因子的表达。细菌中这种依赖群体的基因表达协调被称为“群体感应”(QS)。超过70种革兰氏阴性细菌将N-酰基高丝氨酸内酯(AHLs)用作自诱导物。群体感应信号的抑制可能代表了抗菌治疗的一个新靶点。在此,我们报告了半抗原的设计、合成、抗AHLs单克隆抗体(mAbs)的产生,以及对这些单克隆抗体阻断铜绿假单胞菌群体感应信号和抑制毒力因子表达能力的评估。这些单克隆抗体可被视为未来基于AHL的群体感应研究的工具,这可能有助于深入了解铜绿假单胞菌的发病机制,并最终可能导致开发对抗细菌性疾病的新策略。