Monoclonal antibody targeting the β-barrel assembly machine of Escherichia coli is bactericidal

作者：Kelly M. Storek, Marcy R. Auerbach, Handuo Shi, Natalie K. Garcia, Dawei Sun, Nicholas N. Nickerson, Rajesh Vij, Zhonghua Lin, Nancy Chiang, Kellen Schneider, Aaron T. Wecksler, Elizabeth Skippington, Gerald Nakamura, Dhaya Seshasayee, James T. Koerber, Jian Payandeh, Peter A. Smith, Steven T. Rutherford · 发表于：Proceedings of the National Academy of Sciences · 年份：2018 · DOI：10.1073/pnas.1800043115 · 被引用次数：185 · 研究领域：Escherichia coli research studies、Bacterial Genetics and Biotechnology、RNA and protein synthesis mechanisms

Significance The outer membrane of Gram-negative bacteria presents a formidable barrier to the discovery of new antibiotics needed to combat infections by multidrug-resistant bacteria. Targeting essential proteins or processes directly exposed to the environment could bypass this obstacle. Here, we describe a monoclonal antibody that selectively and potently antagonizes BamA, which folds and inserts integral outer membrane β-barrel proteins, by binding to a surface-exposed BamA epitope and, as a result, inhibits bacterial cell growth. Mechanisms of resistance to the antibody reveal that membrane fluidity affects BamA activity. This antibody validates the potential therapeutic strategy of targeting essential, exposed functions and provides a powerful tool for dissecting the fundamental process of folding integral membrane β-barrel proteins in vivo.