Biology subjects

Osterman, I.

Publications and source records attributed to Osterman, I..

3 recordsLinked to original sources

bioRxiv2024

TIR signaling activates caspase-like immunity in bacteria

Proteases of the caspase family, as well as Toll/Interleukin-1 Receptor (TIR)-domain proteins, have central roles in innate immunity and regulated cell death in humans. In this study we describe a bacterial immune system comprising both a caspase-like protease and a TIR-domain protein. We found that the TIR protein, once it recognizes phage invasion, produces the previously unknown immune signaling molecule ADP-cyclo[N7:1'']-ribose (N7-cADPR). This molecule specifically activates the bacterial caspase-like protease which then indiscriminately degrades cellular proteins to halt phage replication. The TIR-caspase defense system, which we denote as type IV Thoeris, is abundant in bacteria and efficiently protects against phage propagation. Our study highlights the diversity of TIR-produced immune signaling molecules and demonstrates that cell death regulated by proteases of the caspase family is an ancient mechanism of innate immunity.

microbiology↗

bioRxiv2024

Phages reconstitute NAD+ to counter bacterial immunity

Bacteria defend against phage infection via a variety of antiphage defense systems. Many defense systems were recently shown to deplete cellular nicotinamide adenine dinucleotide (NAD+) in response to infection, by breaking NAD+ to ADP-ribose (ADPR) and nicotinamide. It was demonstrated that NAD+ depletion during infection deprives the phage from this essential molecule and impedes phage replication. Here we show that a substantial fraction of phages possess enzymatic pathways allowing reconstitution of NAD+ from its degradation products in infected cells. We describe NAD+ reconstitution pathway 1 (NARP1), a two-step pathway in which one enzyme phosphorylates ADPR to generate ADPR-pyrophosphate (ADPR-PP), and the second enzyme conjugates ADPR- PP and nicotinamide to generate NAD+. Phages encoding the NARP1 pathway can overcome a diverse set of defense systems, including Thoeris, DSR1, DSR2, SIR2-HerA, and SEFIR, all of which deplete NAD+ as part of their defensive mechanism. Phylogenetic analyses show that NARP1 is primarily encoded on phage genomes, suggesting a phage- specific function in countering bacterial defenses. A second pathway, NARP2, allows phages to overcome bacterial defenses by building NAD+ via metabolites different than ADPR-PP. Our findings report a unique immune evasion strategy where viruses rebuild molecules depleted by defense systems, thus overcoming host immunity.

microbiology↗

bioRxiv2023

Phages overcome bacterial immunity via diverse anti-defense proteins

It was recently shown that bacteria employ, apart from CRISPR-Cas and restriction systems, a considerable diversity of phage resistance systems, but it is largely unknown how phages cope with this multilayered bacterial immunity. Here, we analyzed groups of closely related Bacillus phages that showed differential sensitivity to bacterial defense systems, and identified multiple families of anti-defense proteins that inhibit the Gabija, Thoeris, and Hachiman systems. We show that these proteins efficiently cancel the defensive activity when co-expressed with the respective defense system or introduced into phage genomes. Homologs of these anti-defense proteins are found in hundreds of phages that infect taxonomically diverse bacterial species. We show that an anti-Gabija protein, denoted Gad1, blocks the ability of the Gabija defense complex to cleave phage-derived DNA. Our data further reveal an anti-Thoeris protein, denoted Tad2, which is a "sponge" that sequesters the immune signaling molecules produced by Thoeris TIR-domain proteins in response to phage. Our results demonstrate that phages encode an arsenal of anti-defense proteins that can disable a variety of bacterial defense mechanisms.

genetics↗