Prospective and challenges of live bacterial therapeutics from a superhero Escherichia coli Nissle 1917

Escherichia coli Nissle 1917 (EcN), the active component of Mutaflor^(R), is a notable probiotic from Gram-negative to treat Crohn's disease and irritable bowel syndrome. Therefore, a comprehensive genomic database maximizes the systemic probiotic assessment to discover EcN's role in human health. Recently, advanced synthetic and genetic tools have opened up a rich area to execute EcN as "living medicines" with controllable functions. Incorporating unique biomarkers allows the engineered EcN to switch genes on and off in response to environmental cues. Since EcN holds promise as a safe nature vehicle, more studies are desired to fully realize a wide range of probiotic potential for disease treatment. This review aims to deliver a historical origin of EcN, discuss the recent promising genetic toolbox in the rational design of probiotics, and pinpoint the clinical translation and evaluation of engineered EcN in vitro and in vivo. The summary of safety concerns, strategies of biotherapeutics development, and the challenges and prospects of engineered EcN is also concluded.