Whenever we make a call, send a text message or watch a video, some of the energy stored in our cell phone batteries is depleted. Living cells also store energy in the form of "currency" that can be cashed in when needed to power life processes. The main energy currency of all living things on Earth is a molecule called adenosine triphosphate (ATP).
While storing energy in cells with ATP molecules is crucial, it has now been discovered that allowing them to release energy is just as important and could even save lives. In a new study, researchers from the Weizmann Institute of Science in Israel describe a new family of proteins whose members are able to deplete a cell's energy and thus protect it from invaders. They found that this previously unknown immune mechanism does not exist only in single-celled organisms. The mechanism is conserved over more than a billion years of evolution and is utilized by many organisms, from corals to bees. The findings are published in the August 17, 2023 issue of Cell under the title "A conserved family of immune effectors cleaves cellular ATP upon viral infection".
This newly discovered strategy is the latest of more than 100 complex mechanisms used by bacteria in their valiant battle against phages (viruses that attack bacteria). Many of these mechanisms were discovered and described in the laboratory of Professor Rotem Sorek of the Department of Molecular Genetics at the Weizmann Institute of Science.
Like viruses that attack the human body, phages consist of a small amount of protein and a large amount of genetic material (DNA or RNA), which they inject into the bacteria they want to take over. Once this task is accomplished, phages use the bacteria's molecular machinery to replicate themselves over and over again. When they have exhausted the resources of a single bacterium, they tear up the bacterial membrane, break through it, and spread throughout the bacterial colony.
In this new study, these authors focused on a gene that caught their attention - one that mysteriously disabled the phage's ability to replicate itself and infect the rest of the colony. They found that this mysterious gene encodes a protein that cleaves and permanently destroys ATP molecules, thus denying the invading phage the energy it needs to replicate itself. This is an effective immunization strategy. They deduced that the gene plays a key role in the bacterial immune system: without it, phages infecting bacteria would replicate 100 times faster.
Image from Cell, 2023, doi:10.1016/j.cell.2023.07.020.
Dr. François Rousset, a researcher in Sorek's lab, says, "Reducing ATP levels in cells is a simple and brilliant strategy. Phages can't replicate without energy, and bacteria are infected and about to die in any case, so it's best to deplete themselves to prevent phages from replicating and spreading to the rest of the colony."
These authors also found that in some cases, depleting ATP affected the phage's control system, causing this control system to prematurely disrupt the bacterial cell membrane before it had a chance to replicate. This prevented more extensive damage to the colony. Surprisingly, this strategy is much more common than one might think. They scanned genomic databases of tens of thousands of bacterial species and found more than 1,000 immune genes that work in a similar way.
In addition, these authors were surprised to discover a family of proteins called Detocs with the ability to consume ATP, which until then was not even known to belong to the immune system. This suggests that they have discovered a new immune strategy that is present in hundreds of different bacteria and enables them to defend themselves effectively against phages.
However, this new study did not stop at bacteria. The comprehensive analysis conducted by these authors shows that more advanced organisms - fungi, insects (such as bees), corals, sponges and many others - also produce ATP-cutting proteins with immune functions. Although such immune proteins do not exist in humans, they are believed to be ancient precursors to the proteins that make up the human innate immune system.
Sorek says, "Over the past few years, many studies have used knowledge of the advanced biological immune system to reveal the immune strategies used by bacteria. Our new study shows that the vast amount of accumulated knowledge about the bacterial immune system allows us to follow the opposite logic - we can learn about the immune systems of higher organisms by studying the immune systems of bacteria.ATP molecules are among the most widely available molecules in nature, so elucidating their role in immunity could greatly help us understand the myriad of defense strategies."
