Bacterial defense system characterized!

With the aid of highly advanced microscopes and synchrotron sources, researchers have gained seminal insight into how bacteria function as defence mechanisms against attacks from other bacteria and viruses.

The study, which has been published in the renowned journal, Nature Communications, also describes how the defense systems can be activated on cue. This discovery can turn out to be an important cornerstone in fighting diseases in the future.

The researchers have shown how a cell attacked by a virus activates a molecule called COA (Cyclic Oligoadenylate), which in turn activates a so-called protein complex called CSX1 to eradicate the attacker.

'Expressed in popular terms, the CSX1 starts cutting up the intruder. We can see how CSX1 is activated, rotates and starts defending the cell, once COA is activated, the senior author explains.

The researchers have also managed to successfully activate the process themselves. They sent a COA molecule after the protein complex, so to say, and thus started the defense mechanism.

The authors present the structure of Sulfolobus islandicus (Sis) Csx1-cOA4 complex revealing the allosteric activation of its RNase activity. SisCsx1 is a hexamer built by a trimer of dimers. Each dimer forms a cOA4 binding site and a ssRNA catalytic pocket. cOA4 undergoes a conformational change upon binding in the second messenger binding site activating ssRNA degradation in the catalytic pockets.

Activation is transmitted in an allosteric manner through an intermediate HTH domain, which joins the cOA4 and catalytic sites. The RNase functions in a sequential cooperative fashion, hydrolyzing phosphodiester bonds in 5′-C-C-3′. The degradation of cOA4 by Ring nucleases deactivates SisCsx1, suggesting that this enzyme could be employed in biotechnological applications.

'In short, we have found a switch that turns on the cell's defense system when we want it to, and so we can diffuse possible attacks,' the author elaborates.

It is the first time ever that researchers have managed to map and activate a bacterial immune system.

'A few years ago, science wasn't even aware that bacteria had some sort of immune defense system. With this discovery, we have come a great deal further in terms of understanding these mechanisms,' the author says.

Furthermore, the discovery is interesting because the defense system in bacteria resemble in many ways the human innate immune system.

'Therefore, it is also a step along the way of understanding the human immune system better as well as knowing how to fight bacteria and defend oneself against viruses and in the long run even multiple resistance,' Guillermo Montoya says.

The discovery of a bacteria defense system was made possible by using so-called x-ray crystallography. The image of the CSX1protein complex was made possible by the advanced cryogenic electron microscope.

'CSX1 is approximately 0.00005 mm long. This equates cutting one millimetre into 10,000 slices and then placing five pieces on top of each other. We have taken the pictures one by one and made a short film that reveals the activity inside CSX1,' the author explains.

https://healthsciences.ku.dk/newsfaculty-news/2019/09/new-discoveries-map-out-crispr-cas-defence-systems-in-bacteria/