Biology subjects

Hurieva, B.

Publications and source records attributed to Hurieva, B..

4 recordsLinked to original sources

bioRxiv2026

Conserved catalytic activity of immune TIR domains in animals

The Toll/interleukin-1 receptor (TIR) domain is important for immune signaling across bacteria, plants, and animals. In human innate immunity, TIR domains are known to function as adaptors mediating protein-protein interactions, yet studies in bacteria and plants revealed that TIR domains often act as enzymes that produce immune signaling molecules. Here, we show that TIR domains from evolutionarily diverse animals have conserved active sites, implying that they can function as enzymes. In vitro experiments with animal TIRs show that the TIR domain of several Toll-like receptors (TLRs), including that of human TLR4, can produce cyclic ADP-ribose (cADPR), revealing an enzymatic activity previously unknown for TLR TIRs. We show that production of cADPR is a conserved feature of TIR domains across the animal tree of life, implying a role for this molecule in animal TIR signaling. Finally, we report a TIR domain from green algae that synthesizes 3'cADPR, suggesting conservation of 3'cADPR signaling between bacteria and eukaryotes. Our results reveal that the catalytic activity of TIR domains is widespread in animals and conserved across the tree of life.

immunology↗

bioRxiv2026

Bacterial defense via RES-mediated NAD+ depletion is countered by phage phosphatases

Many bacterial defense systems restrict phage infection by breaking the molecule NAD+ to its constituents, adenosine diphosphate ribose (ADPR) and nicotinamide (Nam). To counter NAD+ depletion-mediated defense, phages evolved NAD+ reconstitution pathway 1 (NARP1), which uses ADPR and Nam to rebuild NAD+. Here we report a bacterial defense system called aRES, involving RES-domain proteins that degrade NAD+ into Nam and ADPR-1-phosphate (ADPR-1P). This molecule cannot serve as a substrate for NARP1, so that NAD+ depletion by aRES defends against phages even if they encode NARP1. We further discover that some phages evolved an extended NARP1 pathway capable of overcoming aRES defense. In these phages, the NARP1 operon also includes a specialized phosphatase, which dephosphorylates ADPR-1P to form ADPR, a substrate from which NARP1 then reconstitutes NAD+. Other phages encode inhibitors that directly bind aRES proteins and physically block their active sites. Our study describes new layers in the NAD+-centric arms race between bacteria and phages and highlights the centrality of the NAD+ pool in cellular battles between viruses and their hosts.

microbiology↗

bioRxiv2025

Systematic discovery of TIR-based immune signaling systems in bacteria

Toll/interleukin-1 receptor (TIR) domains are important for immune signaling across humans, plants and bacteria. These domains were recently found to produce immune signaling molecules in plant immunity as well as in a family of bacterial defense systems called Thoeris. Here, we systematically scanned bacterial defense islands to identify anti-phage defense systems involving TIR-mediated signaling. We detected numerous configurations of such systems in bacterial genomes, involving [~]30 different protein effectors predicted to respond to TIR-produced immune signals. We experimentally verified 15 new TIR-containing systems, showing that they provide defense against phages through effector protein domains not previously known as associated with immunity. Further biochemical analyses revealed bacterial Thoeris systems that generate 2'cADPR, an immune signaling molecule central to plant immunity. We also discover multiple types of Thoeris that drive antiphage defense via canonical cADPR, a signaling molecule known to mediate human innate immunity. Our studies show that TIR-based immune signaling systems exist in at least 8% of bacterial genomes, and suggest conservation of TIR-derived immune signals across the tree of life.

microbiology↗

bioRxiv2023

Cell-cycle status of male and female gametes during Arabidopsis reproduction

Fertilization in Arabidopsis thaliana is a highly coordinated process that begins with a pollen tube delivering the two sperm cells into the embryo sac. Each sperm cell can then fertilize either the egg or the central cell to initiate embryo or endosperm development, respectively. The success of this double fertilization process requires a tight cell cycle synchrony between the male and female gametes to allow karyogamy (nuclei fusion). However, the cell cycle status of the male and female gametes during fertilization still remains elusive as DNA quantification and DNA replication assays have given conflicting results1-4. Here, to reconcile these results, we quantified the DNA replication state by DNA sequencing and performed microscopic analyses of fluorescent markers covering all the phases of the cell cycle. We show that male and female gametes in Arabidopsis are both arrested prior to DNA replication at maturity and initiate their DNA replication only during fertilization.

plant biology↗