In many of my previous posts I talked about how bacteria fight each other using one of their many killing devices (for example here or here). I also described a few strategies of how bacteria deliver toxins into competing bacteria (like here or here). And I always say that these toxins are the ones that finally kill the prey bacterium.
So the questions I want to answer this week are: what does this toxin do once it reached the prey bacterium? How does a toxin kill a bacterium? And why is the toxin-producing bacterium not killed by the toxin?
Please be reminded that here I will only talk about toxins that can harm bacteria. Bacteria also produce toxins that they then deliver into human cells to survive and strive within the human body. These kind of toxins are not discussed at this point.
The last question is already fairly easy. Whenever a bacterium produces a toxin, it always also produces a so-called immunity or anti-toxin (in yellow in the bacterium on the far right). This immunity binds the toxin and neutralises it, so that it does not become a danger to the producing cell.
Let’s start by explaining what sort of compound a toxin actually is.
Most toxins are proteins with enzymatic activities. In general, enzymes catalyse biological reactions by binding a specific substrate, fusing it to another substrate or breaking the substrate apart. The functioning of enzymes is what keeps a cell alive, because enzymes are required for cell respiration, cell growth, cell division etc.
However, enzymatic activities of toxins generally focus on breaking up components that are essential for life. There are a few classes of bacterial toxins and more and more are being discovered.
Here, I will explain the most important ones and little sketches will help understanding what each toxin is doing.
As DNA being “the molecule of life”, it makes perfect sense that destroying this essential molecule will lead to cell death of the prey bacterium. Indeed, the most potent toxins are nucleases that break down the DNA inside a bacterium. If there is no DNA inside a bacterial cell, the cell cannot produce any proteins and enzymes to keep the cell alive.
To make proteins out of DNA, another step is essential: the production of RNA out of DNA. RNA and DNA are both nucleic acids (which is why these toxins are called nucleases), but RNA is the transcript for the cell machinery to produce proteins. Hence, some nucleases do not break down DNA, but they specifically chew up the RNA in a bacterial cell.
The outcome is basically the same; the bacterium cannot produce any protein and will die eventually.
So, nucleases break down either DNA or RNA to restrict a bacterium from protein production resulting in cell death.
cell-envelope degrading toxins
The cell envelope is what keeps all the components within the bacterial cell together and protects a cell from the environment. Just as your skin keeps your whole body together and protects it from the outside. This makes the bacterial cell envelope another promising target to destroy to kill a bacterium.
Depending on whether a bacterium belongs to the Gram-positive or Gram-negative category, it has one or two layers of cell envelope. Gram-positive bacteria usually have one thick and rigid cell wall, while Gram-negative bacteria have two cell membranes between which is the so-called periplasm. Within the periplasm is some kind of loose mesh that holds the inner and outer membrane together.
Lots of toxins were found that can break down any of these layers. Some toxins can specifically chew up the thick and rigid cell wall of Gram-positive bacteria. Other toxins aim at one of the two membranes of Gram-negative bacteria or the mesh component in the periplasm.
In each case, the toxin has an enzymatic activity, that breaks down the molecule of which the layer is made.
Pore-forming toxins actually do not have an enzymatic activity, but they have the unique ability to form holes in a bacterial cell envelope. When a bacterium has a few holes in its cell envelope, basically all the cell content can leak to the outside. Also, the liquid from the environment can stream into the cell and eventually burst the prey cell.
Thus, some toxins target the bacterial cell envelope so that a bacterium looses its shape and protection.
These kind of toxins are the most versatile, since many ways exist to inhibit the actual functioning of a cell. I will just discuss a few here, but also keep in mind that in many cases it is still not clearly understood how these types of toxins actually work.
However, most of these toxins have one thing in common: They break down an essential molecule which inhibits the bacterium from functioning properly.
For example, to produce proteins every cell requires ATP, which is the molecule in which cells store energy. One toxin was recently discovered that breaks down ATP molecules within a prey cell. This makes it impossible for the prey to produce any more protein, and we already know how his story ends.
Other toxins were found that break down essential cofactors. Cofactors are vitamins, which every cell requires for example for cell respiration. If a cell cannot perform cell respiration, it does not produce ATP. And if a cell does not have any ATP? you know it 🙂 !
You see the pattern here, right?
Whenever a bacterium delivers a toxin into a prey bacterium, it wants to hurt it real bad. This means, that a toxin generally targets any of the essential components of the prey bacterium to make sure there is no chance of survival.
So, if you now go back to any of the other “killer” articles, you might appreciate how important those killer machines are for bacteria 😉