Diversity-generating retroelements for programmable targeted hypermutagenesis - Nature Biotechnology Diversity-generating retroelements are engineered for directed evolution in E.coli.

🔈Paper out! We turned the most fascinating phage host-switch mechanism, diversity-generating retroelements, into a programmable mutagenesis tool, DGRec. You can perform targeted hypermutation of any 50-200bp sequence directly in vivo in E. coli www.nature.com/articles/s41...

Intra-species competition combats vancomycin-resistant enterococci - PubMed Vancomycin-resistant <i>Enterococcus</i> (VRE) is a leading cause of multidrug-resistant infections in hospitalized patients, yet no reproducible microbiota therapies exist to selectively displace it. Here we harness intra-species competition within <i>Enterococcus</i> to suppress VRE colonization. …

If you found this interesting, check out the full paper: pubmed.ncbi.nlm.nih.gov/41872068/

Huge thanks to @naamagz.bsky.social my PhD PI. and the whole team: Tal, Rawi, Shaqed, Omri, and Aviv for making this work possible!
@shaqedc.bsky.social

In conclusion, we found a strain that can outcompete VRE in vivo, but is itself outcompeted by other non-antibiotic-resistant strains. Competition is complicated! This raises the question of what the right approach is for designing a probiotic treatment.

We also confirmed this by qPCR, pitting X98 against these other bacteria one-on-one. Indeed, several strains appear to outcompete it.

Interestingly, when given together with other non-resistant strains, the effect disappears.

Here you can see sequencing data across multiple experiments: X98 almost disappears after 14 days of co-culture in the consortium.

It can even outcompete other VRE strains! (Though we didn't test those in vivo...)

E. faecalis X98, when given together with V583, a common VRE strain, completely eradicates it.

To improve this treatment, we screened different Enterococcus strains to find better competitors that could outcompete the VRE strain even inside the mouse gut.

The best competitor was E. faecalis X98, our new sheriff in the gut:

We tried to treat them using phages and known antagonistic Enterococci. We even tried pre-exposing these non-antibiotic-resistant bacteria to phages before the competition to enhance the competitive effect.

But this did not help. The VRE was cleared in vitro, but not inside the mouse gut.

Vancomycin Resistant Enterococci are dangerous bugs. They can colonize the gut and are associated with serious health risks such as endocarditis, sepsis and death.
They are labelled by the CDC as a serious health threat.

Yesterday our paper "Intra-species competition combats vancomycin-resistant enterococci" was published online.
We found an enterococcal strain that can outcompete a VRE strain, but loses its potency when given with other non resistant Enterococci.

Here is a high res img from the battle in the gut: