Mimee and co-workers, from the M.I.T Synthetic Biology Center, published in the new journal Cell Systems a novel set of genetic technologies for the manipulation of the mammalian commensal bacterium Bacteroides thetaiotaomicron. The authors succeeded in modulating the constitutive gene expression of B. thetaiotaomicron by using the novel CRISPR-Cas9 technologies, in particular the CRISPR interference (CRISPRi) methodology. This technique has revolutionized genome editing and allows regulating gene expression at target user-defined DNA sequences by blocking transcription by RNA polymerase.
The authors reported a library of biological parts, such as constitutive or inducible promoters, that would permit both the construction of synthetic gene circuits and the study of biological networks. To test the functionality of their tools, they designed programmable CRISPRi-mediated gene knockdown for synthetic constructs, and subsequently, they studied the function of that genetic parts in a context of complex microbiota, using mice colonized with the modified B. thetaiotaomicron strain after antibiotic treatment.
These results presented a new way to explore cellular sensing, increasing our understanding of the host-microbe interface in the gut, and the potential to change the gut ecosystem.