Repurposing a Two-Component System-Based Biosensor for the Killing of Vibrio cholerae
Repurposing a Two-Component System-Based Biosensor for the Killing of Vibrio cholerae
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DOI：
10.1021/acssynbio.7b00058
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发表时间：
2017-07-01
影响因子：
4.7
通讯作者：
Poh, Chueh Loo
中科院分区：
文献类型：
--
作者：
Jayaraman, Premkumar;Holowko, Maciej B.;Poh, Chueh Loo
迫切需要控制霍乱的新战略。本研究开发了一种在野生型大肠杆菌菌株中的体外概念验证感杀系统，以使用合成生物学方法靶向致病病原体霍乱弧菌。我们的工程E.大肠杆菌通过其群体感应分子CAI-1特异性地检测霍乱弧菌，并通过表达裂解蛋白YebF-Art-085来响应，从而自我裂解以释放杀伤蛋白Art-085来杀伤霍乱弧菌。对于这份报告，我们分别表征了YebF-Art-085和Art-085的表达及其与我们先前开发的霍乱弧菌生物传感电路偶联时的活性。我们发现，在霍乱弧菌上清液的存在下，我们的工程化大肠杆菌中的最终整合的感杀系统。coli能有效抑制霍乱弧菌的生长。这项工作代表了迈向一种新的益生菌治疗模式的第一步，这种治疗模式可能在未来预防和治疗霍乱。
New strategies to control cholera are urgently needed. This study develops an in vitro proof-of-concept sense-and-kill system in a wild-type Escherichia coli strain to target the causative pathogen Vibrio cholerae using a synthetic biology approach. Our engineered E. coli specifically detects V. cholerae via its quorum-sensing molecule CAI-1 and responds by expressing the lysis protein YebF-Art-085, thereby self-lysing to release the killing protein Art-085 to kill V. cholerae. For this report, we individually characterized YebF-Art-085 and Art-085 expression and their activities when coupled to our previously developed V. cholerae biosensing circuit. We show that, in the presence of V. cholerae supernatant, the final integrated sense-and-kill system in our engineered E. coli can effectively inhibit the growth of V. cholerae cells. This work represents the first step toward a novel probiotic treatment modality that could potentially prevent and treat cholera in the future.