Project description:Retrons are bacterial genetic elements that encode a reverse transcriptase and, in combination with toxic effector proteins, can serve as antiphage defense systems. However, the mechanisms of action of most retron effectors, and how phages evade retrons, are not well understood. Here, we show that some phages can evade retrons and other defense systems by producing specific tRNAs. We find that expression of retron-Eco7 effector proteins (PtuA and PtuB) leads to degradation of tRNA-Tyr and abortive infection. The genomes of T5 phages that evade retron-Eco7 include a tRNA-rich region, including a highly expressed tRNA-Tyr gene, which confers protection against retron-Eco7. Furthermore, we show that other phages (T1, T7) can use a similar strategy, expressing a tRNA-Lys, to counteract a tRNA anticodon defense system (PrrC170).

2024-09-12 | GSE229290 | GEO

Acinetobacter baumannii

Project description:Acinetobacter phages Genome sequencing and assembly

| PRJNA608808 | ENA

Rational in vitro design of a two-phage cocktail against a contemporary Acinetobacter baumannii strain recovered from a burned patient at CHUV

Project description:Acinetobacter baumannii is currently a major threat to human health. With the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, the development of complementary strategies is needed. A promising complimentary and realistic strategy could be phage therapy, which uses bacteriophages (phages), i.e viruses that specifically infect and kill bacterial cells during their life cycle. We designed a two-phage cocktail highly efficient against an extensive drug-resistant (XDR) A. baumannii isolate collected from a patient with burn wound infection at CHUV (termed Ab125). A first in vitro screen of our collection of 34 different phages identified only phage vB_AbaM_3098 as capable of lysing Ab125. However, quick selection of phage-resistant clones (termed Ab139) occurred. Comparative genomics and proteomics between Ab125 and Ab139 revealed several key variations. Very interestingly, we observed that Ab139 became susceptible to six different phages in the collection, otherwise inactive on Ab125. Phage-resistance was also selected when Ab139 was challenged with either of the six phages, with bacterial regrowth observed between 14 h and 16 h. However, combination of vB_AbaM_3098 and vB_AbaM_3014 led to a two-phage cocktail capable of totally inhibiting the growth of Ab125. Treatment with the phage cocktail led to 90% survival after 5 days in the in vivo Galleria Mellonella model of infectious diseases, compared to 0% in the non-treated group. We show that the combination of a phage that only slightly shifted the in vitro bacterial growth curve with an “inactive phage” led to the formulation of a highly bactericidal phage cocktail against Ab125. We then tested the therapeutic potential of the assembled cocktail in synergy with antibiotics and found a synergy with colistin. This work highlights the complexity sometimes involved in the assembly of potent phage cocktail.

2025-12-08 | PXD062593 | Pride

Phage-encoded sigma factors alter bacterial dormancy

Project description:By entering a reversible state of reduced metabolic activity, dormant microorganisms are able to contend with suboptimal conditions that would otherwise reduce their fitness. In addition, certain types of dormancy like sporulation, can serve as a refuge from parasitic infections. Phages are unable to attach to spores, but their genomes can be entrapped in the resting structures and are able to resume infection upon host germination. Thus, dormancy has the potential to affect both the reproductive and survival components of phage fitness. Here, we characterized the distribution and diversity of sigma factors in nearly 3,500 phage genomes. Homologs of bacterial sigma factors that are responsible for directing transcription during sporulation were preferentially recovered in phages that infect spore-forming hosts. While non-essential for lytic infection, when expressed in Bacillus subtilis, we demonstrate that phage-encoded sigma factors activated sporulation gene networks and reduced spore yield. Our findings suggest that the acquisition of host-like transcriptional regulators may allow phages to manipulate the expression of complex traits, like the transitions involved in bacterial dormancy.

2021-11-05 | GSE187004 | GEO

Acinetobacter phage Acba_3

Project description:Acinetobacter phage Acba_3, genome sequencing and assembly

| PRJNA912606 | ENA

Acinetobacter phage Ab_WF01

Project description:Acinetobacter phage Ab_WF01 Genome sequencing and assembly

| PRJNA946663 | ENA

Acinetobacter phage EAb13

Project description:Acinetobacter phage EAb13 Genome sequencing and assembly

| PRJNA948145 | ENA