by Mara Casebeer

Most bacteria, like the common E. coli, are around a micron in length – less than a tenth of the width of a strand of human hair and invisible without a microscope.

Recently, scientists discovered a bacterium, Candidatus (Ca.) Thiomargarita magnifica, that is almost 10,000 times longer than E. coli. Ca. T. magnifica cells were found attached to sunken leaves in the mangroves of Guadeloupe, a sulfuric marine environment. Amazingly, this bacterium is visible to the human eye in the form of long filamentous strands (Figure 1). 

Figure 1. Size comparison between an atom, protein, bacteria, hair, and Ca. T. magnifica. The ruler is in log scale, meaning one tick up is ten times bigger than the previous!

When scientists discovered this new species, they originally thought it was some kind of fungus or worm, and were shocked to discover that it was in fact a bacterium after analyzing its genome. This is incredibly surprising because the size of this bacterium is two orders of magnitude above the previously predicted maximum size. 

So, why are most bacteria around a micron long? And how is Ca. T. magnifica almost three centimeters long?

Why are bacteria the size that they are?

There are two main reasons why most bacteria are around a micron in length.

First, bacteria can’t get too small because they have to cram all of their genetic material in without leaving any important genes out. They must also contain all of the necessary components to express those genes. Some of the smallest bacteria, including Candidatus Actinomarina minuta, are just 1% of the volume of E. coli.

On the other hand, bacteria also can’t get too big because they have to be able to transport components from one end of the cell to another. This is one of the key differences between eukaryotic and prokaryotic cells. 

Eukaryotic cells, like the cells that make up our body, have active transport mechanisms, meaning that they use energy (like ATP) to move materials. Unlike eukaryotic cells, bacteria, which are prokaryotic, use a passive transport method called diffusion to move materials around the cell. Diffusion is the random movement of particles that results in an average motion from higher concentration to lower concentration. Diffusion is much slower than active transportation, so it is important for bacteria to be able to move the materials required around in a reasonable amount of time.

Another difference between eukaryotic and prokaryotic cells is that eukaryotic cells have membrane-bound organelles, allowing materials to be partitioned within the cell and separated by a barrier. Bacteria don’t normally have membrane-bound organelles, such as mitochondria, which is an organelle famous for being the “powerhouse of the cell” by being the site of energy production. This means that mitochondria are more accurately the powerhouse of eukaryotic cells.

Why is the diffusion limit so important?

Diffusion becomes difficult when distances get large. Mathematically, we can use the Stokes-Einstein equation to estimate the amount of time it takes a particle to diffuse. The time to diffuse is determined by the distance a particle has to travel, squared. In other words, the time for a protein to travel a distance r is proportional to r2. This diffusion also depends on the size and the shape of the particle diffusing, as well as the material that it is diffusing through – these factors are represented in the formula by the diffusion coefficient (D). For a protein diffusing through the cytoplasm, the material inside a cell, the diffusion coefficient is about 10 μm2/s.

For an E. coli cell that has a length of r = 1 μm, it would take approximately 10 ms for a protein to diffuse. A HeLa cell, which is a human cell line commonly used in research, has a radius of ~20 μm, so it would take ~10 s for a protein to diffuse across it. For Ca. T. magnifica, with a length of a centimeter, it would take 106 seconds, or around 11 days! Based on these back-of-the envelope calculations, Ca. T. magnifica, and other large bacteria, must have methods to beat the diffusion limit that typically restricts bacterial size (Figure 2).

Figure 2. It would take a protein around 11 days to diffuse across Ca. T. magnifica! For a much smaller E. coli cell, it would only take around 10 ms.

How does Ca. T. magnifica beat this diffusion limit?

The scientists who discovered Ca. T. magnifica determined that several of its unique characteristics may help explain its large size.

One way that Ca. T. magnifica gets around the diffusion limit is by reducing the distance that proteins and metabolites have to diffuse through. To do this, this bacterium has a large space in its center called the central vacuole, which reduces the volume of the cytoplasm. Instead of filling the entire cell, the cytoplasm is pushed to the edges of the cell. According to the scientists, the central vacuole makes up 73.2 ± 7.5 % of the bacterium’s total volume.

Another way Ca. T. magnifica reduces the distance that components must travel is by compartmentalization. Ca. T. magnifica has DNA and ribosomes within membrane-bound organelles called “pepins”. As mentioned above, this is very unusual for bacteria, since prokaryotes typically don’t have membrane-bound organelles. Having DNA and ribosome compartmentalization means that these components don’t have to diffuse to find each other.

ATP synthase is a protein that is responsible for producing ATP, the energy currency of cells, and is localized to mitochondria in eukaryotic cells. Since bacteria don’t have mitochondria, most bacteria have ATP synthase localized to the cell envelope, a membrane that goes around the inner circumference of bacteria. Ca. T. magnifica, however, has ATP synthases around its pepins and in its complex membrane network in the cytoplasm. This allows the bacteria to be less dependent on their surface area to volume ratio. Rather than being restricted by the surface area of the cell envelope, Ca. T. magnifica can use the larger surface area of the internal membranes to house more ATP synthase. 

Finally, Ca. T. magnifica is a highly polyploid cell, meaning a single bacterium has many identical copies of its genome. Polyploidy is common in large bacteria because it more easily supports cellular growth – the cellular machinery inside the bacteria can produce more proteins at a time and have more localized responses to stimuli.

What does this mean for scientists?

Ca. T. magnifica is the largest known giant bacterium to date, beating other giant bacteria by 50x. This magnificent organism beats the diffusion limit by having a large central vacuole, enabling energy production in the cytoplasm, and compartmentalizing DNA and ribosomes. Ca. T. magnifica challenges the concept of what a bacterial cell is with these adaptations, and outperforms predictions of the largest possible bacterium.

The discovery of this large bacterium demonstrates that there is still much to learn about earlier-evolved forms of life, and that there is more bacterial diversity than we could have imagined. As scientists continue to find and characterize new bacteria, perhaps there are even larger bacteria than Ca. T. magnifica waiting to be discovered.

 Mara Casebeer is a PhD student in the Biophysics Program at Harvard University.

For More Information:

  • You can read the original article here!
  • To read more about another large bacteria with polyploidy check out this article. 
  • Here’s a cool article about really large viruses!

One thought on “How this Long Bacterium Beats the Diffusion Limit

  1. If, on the contrary, we are dealing with a very small bacterium with long runs. If diffusion were the single major constraint on cell size and shape, then cells should either be thin and flat or have numerous long.

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