麻豆淫院

A research team has uncovered a previously unknown type of immune signaling molecule鈥攁 novel compound combining histidine and ADP-ribose鈥攑roduced by bacteria's Thoeris II defense system in response to viral infection. This finding expands our understanding of bacterial immunity and may pave the way for innovative tools in biotechnology, gene editing, and antimicrobial therapy.

The paper, titled "TIR domains produce histidine-ADPR as an immune signal in bacteria," is in the journal Nature, and the team includes scientists at Vilnius University's Life Sciences Centre (VU LSC), together with colleagues from the Weizmann Institute of Science (Israel) and Harvard Medical School.

The discovery sheds light on how bacteria, much like humans, communicate viral threats at the molecular level鈥攊n this case, triggering a self-sacrificing response to halt virus spread and protect bacterial populations. Beyond its fundamental significance, the finding opens exciting avenues for rethinking immune mechanisms and virus-host interactions.

This newly identified molecule is remarkable for its unique structure, linking two biologically essential components: histidine, an amino acid used to build proteins, and an adenine nucleotide, a building block of RNA. Until now, all known signaling molecules were composed solely of nucleotides. This discovery significantly broadens the scientific understanding of the diversity of immune signaling mechanisms in nature.

Like humans, animals, and plants, bacteria are constantly threatened by viruses. Over the course of evolution, they have developed a wide range of defense systems鈥攕ome of which served as the evolutionary precursors to immune system components in higher organisms. Interest in bacterial antiviral systems surged after their applications were realized in genetic engineering. Landmark examples such as restriction鈥搈odification systems and CRISPR-Cas "molecular scissors" have even been recognized with Nobel Prizes.

To date, scientists have identified over 250 distinct antiviral defense systems in bacteria. Following previous work by Vilnius University researchers showing that small molecules can serve as infection signals within these systems, attention turned to exploring the diversity of such signaling mechanisms.

Discoveries like this not only deepen understanding of bacterial immune strategies but also lay the groundwork for innovations in genetic engineering, biotechnology, and even the development of new antibacterial therapies.

In this latest study, Dr. Tamulaitien臈's group closely examined the Thoeris II system, composed of a sensor protein (TIR), which detects viruses, and a transmembrane effector protein (Macro), which receives the signal and triggers a response. Upon detecting viral infection, the TIR sensor synthesizes a unique small molecule signal鈥擧is-ADPR.

"This 'message'鈥攖he signaling molecule鈥攊s recognized by the system's effector, the Macro protein, which is embedded in the bacterial cell membrane," explains Dr. Tamulaitien臈.

"Once it receives the signal, the Macro proteins start to assemble with each other, damaging the cell membrane. In this way the infected bacterium sacrifices itself before the virus can replicate, allowing neighboring bacteria to survive and preserve the population."

Using X-ray crystallography, the VU LSC team determined the structure of the effector protein bound to the new signaling molecule.

Meanwhile, the team at the Weizmann Institute confirmed that this molecule is indeed synthesized in bacteria upon viral infection. Researchers at Harvard Medical School revealed the structure of a viral antiThoeris "sponge" protein鈥攁 countermeasure the virus uses to evade the defense system鈥攚ith His-ADPR bound inside.