Speaker
Description
Bacterial populations are shaped by antagonistic interactions, including phage predation and interbacterial competition mediated by toxins such as colicins. However, phages are usually used as natural bacterial killers rather than as programmable tools. Here, using uropathogenic Escherichia coli as a model, we show that broad-host-range phages can report phage-host interactions and constrain resistance emergence by delivering antibacterial toxins.
First, we isolated two naturally broad-host-range phages infecting uropathogenic E. coli and engineered them using CRISPR-assisted methods. NanoLuc reporter versions enabled susceptibility testing within ca. 6 h and collectively identified infection of 70% of an in-house uropathogenic E. coli collection (n = 60), with reporter activity closely matching plaquing host range.
Second, we engineered colicin-producing phages that couple viral predation to colicin-mediated bystander killing. Compared with wild-type phages, they reduced the emergence of resistant bacteria both in rich medium and in human urine, suggesting that phage-delivered toxins can reshape resistance dynamics in an infection-relevant environment.
Together, our results show that phages can be redesigned beyond strain-specific antimicrobials into tools that report infection networks and connect viral predation to interbacterial competition to limit resistance emergence.
