ena-STUDY-HARVARD MEDICAL SCHOOL-27-08-2018-17:51:40:244-206
Engineered communication elements for bacteria in the gut, using genome-integrated single copy circuits.
The gut microbiome is intricately involved with establishing and maintaining the health of the host. Engineering of gut microbes aims to add new functions and expand the scope of control over the gut microbiome. To create systems that can perform increasingly complex tasks in the gut, it is necessary to harness the ability of the bacteria to communicate in the gut environment. Interestingly, acyl-homoserine lactone (acyl-HSL)-mediated Gram-negative bacterial quorum sensing, a widely-used mode of inter-cellular signaling system in nature, has not been identified in normal healthy mammalian gut. It remains unknown whether the gut bacteria that do not natively use quorum sensing can be engineered to successfully signal to other bacteria using acyl-HSLs in the gut environment. Here, we repurposed quorum sensing to create an information transfer system between native gut Escherichia coli and attenuated Salmonella enterica serovar Typhimurium. Specifically, we functionalized one species with inducible signal production and the other with signal detection and recording using genomically integrated circuits. The information transfer system demonstrated successful intra-and inter-species signaling in the murine gut. This study provides a basis for further understanding of inter-bacterial interactions in an otherwise hard-to-study environment as well as a basis for further investigation of the potential of acyl-HSLs as inter-cellular signaling molecules of engineered gut consortia.
The gut microbiome is intricately involved with establishing and maintaining the health of the host. Engineering of gut microbes aims to add new functions and expand the scope of control over the gut microbiome. To create systems that can perform increasingly complex tasks in the gut, it is necessary to harness the ability of the bacteria to communicate in the gut environment. Interestingly, acyl-homoserine lactone (acyl-HSL)-mediated Gram-negative bacterial quorum sensing, a widely-used mode of inter-cellular signaling system in nature, has not been identified in normal healthy mammalian gut. It remains unknown whether the gut bacteria that do not natively use quorum sensing can be engineered to successfully signal to other bacteria using acyl-HSLs in the gut environment. Here, we repurposed quorum sensing to create an information transfer system between native gut Escherichia coli and attenuated Salmonella enterica serovar Typhimurium. Specifically, we functionalized one species with inducible signal production and the other with signal detection and recording using genomically integrated circuits. The information transfer system demonstrated successful intra-and inter-species signaling in the murine gut. This study provides a basis for further understanding of inter-bacterial interactions in an otherwise hard-to-study environment as well as a basis for further investigation of the potential of acyl-HSLs as inter-cellular signaling molecules of engineered gut consortia.