Bacterial infection is one of the leading causes of morbidity and mortality worldwide, and the use of antibiotics is the main therapy for preventing and treating bacterial infection. However, overuse of antibiotics leads to antibiotic resistance, which is a great public health threat. In recent years, using engineered bacteria to treat bacterial infection has gained widespread attention.
Scientists have constructed a strain of engineered E. coli TOP10 that introduces the PLasI promoter induced by acyl-homoserine lactones (AHLs) of Pseudomonas aeruginosa, which drives the expression of gene circuits. In this system, the constitutive tetR promoter initiates transcription, and the produced transcription factor LasR binds to AHL 3OC12HSL, activating the kill and lysis switch, leading to the production of Pyocin S5 protein and E7 lysis protein in the E. coli host. The E7 lysis protein is responsible for breaking down the E. coli host, releasing the Pyocin S5 to kill P. aeruginosa specifically. In vitro studies have shown that the engineered E. coli can significantly inhibit up to 99% of P. aeruginosa growth.
Fig. 1 Design of gene circuit in Escherichia coli for specific killing of Pseudomonas aeruginosa. (Gupta, S; et al. 2013)
Based on the above, the researchers further improved the engineered strain by using ECN as the host cell and conducting experiments to prevent P. aeruginosa gut infections in animal models. Compared to the previous engineered bacteria modification system, they introduced an additional antimicrobial peptide, dispersin B, to break down mature biofilms. The results showed that in a C. elegans model of P. aeruginosa infection, the survival rate of the treatment group increased by more than twice, and in a mouse model of P. aeruginosa infection, the treatment group's P. aeruginosa level decreased by 77% compared to the control group.
Another team of researchers designed an engineered E. coli strain that interferes with quorum sensing to prevent Vibrio cholera from toxin production, which enhances the survival rate of young mice models and reduces toxin formation.
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