Multicellular bacteria

Part of my NatSci course at the moment involves group supervisions, which are made up of around ten people; a mix of students and faculty (all from the Biochemistry department). About halfway through last term we had a supervision about nuclei, and one of the supervisors raised the question, "Is it possible to be multicellular without a nucleus?" (by nucleus he meant chromosomes wrapped up in a membrane, rather than the bacterial arrangement of coiled up DNA loosly attached to the outer cell membrane). His opinion, and the overall consensus that the group seemed to come too, was no, they didn't. I managed to get a few words in about bacterial hunting packs, and sporulation and things, but they weren't really convincing enough. Also I am still just a little Lab-Ratting undergrad obsessed with bacteria, the group knows this and the general opinion seems to be that I see bacteria everywhere now. Even in multicellular form :p

Which was why I was very glad to come across a paper last week that reviewed in great detail a bacteria that is multicellular beyond all reasonable doubt. They do exist, and I feel very rightous about the whole thing, even if I'm not quite brave enough to bring it back up in supervisions.

First, a brief step back to consider just what makes something multicellular. After all, just having lots of cells in close proximity is not enough, otherwise a large colony of Staph aureus, or bits of swept up dried insect would count as multicellular. True multicellularity requires the following:

• Cell-cell adhesion: the cells must be stuck together in a fairly permanent manner
• Intercellular communication: the cells must be able to signal to each other
• Cell differentiation: probably the more important point, the cells must be doing different jobs, and must depend on the surrounding cells to survive.

Can bacteria do all that? Not very many of them can, true, or there would be large multicellular bacterial 'animals' roaming the plains. But there are a number of photosynthetic bacteria are able to form truly multicellular structures, albeit rather small ones:

Those long chains are technically all one organism, a photosynthesising cyanobacteria. The outer cell wall surrounds the whole organism in one continual envelope, and fulfills the first requirement for multicellularity. The arrows point towards larger cells which fulfill the third, these cells are different from the ones surrounding them, they have differentiated to form specialised cells whose only job is to uptake nitrogen and 'fix' it into a usable form.

The reason they've done this is simple, the enzyme required to fix nitrogen (i.e turn it from a useless inorganic form into a usable organic form) does not work in the presence of oxygen, which unfortunately is needed for respiration. That's why most animals and plants can't fix nitrogen and instead rely on food sources, or surrounding soil bacteria. Bacteria respond to this problem either by becoming totally anaerobic (not using any oxygen at all), or differentiating.

(There is a third strategy, which is to become a nitrogen fixing bacteria by night, and an aerobically respiring bacteria by day, but this requires huge amounts of energy as it means that the cell has to do a complete enzyme turnover every twelve hours)

The differentiated cell is called a heterocyst. It has a thicker cell wall to stop oxygen diffusing into the cell, and all cellular processes that might produce oxygen have been removed. Once the cell has turned into a heterocyst it cannot change back again, and is completely dependant on the cells surrounding it for the products of respiration (which it cannot carry out by itself) likewise, the surrounding cells are dependant on the heterocyst for the provision of nitrogen.

In order for the bacteria to survive, both cells are therefore vital. Furthermore the patterning of these cells are vital, having three heterocysts in a row would mean the one in the middle would be deprived of energy and could die. Each heterocyst must be surrounded by normal respiring cells, and they must also be at regular intervals, to provide nitrogen for all the cells in the organism.

This is where the cell signalling comes in. Heterocysts are created when the cells are being starved for nitrogen. Low levels of nitrogen lead to the activation of a protein called NctA, which activates another protein called hetR. These two proteins both lead to more production of each other in a positive feedback loop, until the levels of both are high enough to turn on the genes that will turn the cell into a heterocyst. It also turns on two other important genes; PatA and PatS.

PatS suppresses heterocyst formation, and this diffuses out into the surrounding cells, preventing them from differentiating. The function of PatA is a little uncertain, but it is thought to stop PatS from having an effect in the heterocyst cell itself. This means that the heterocyst will be surrounded by non-differentiated cells, which can supply it with all the energy it needs, and is shown schematically below:

As well as heterocysts, individual cells can also differentiate into other structures, such as spore like cells, which in times of nutritional stress will break up and lie dormant, turning back into fully functioning cells (and replicating to produce a fully functioning organism) when conditions improve. Several cyanobacteria can also form little lines of very small cells, called hormogonia, which have a variety of interesting functions. They show gliding motility (using either pili or slime) and can produce internal gas vesicles, which makes them bob up to the surface in water. Hormogonia are also the first infection units in symbiosis. When a cyanobacteria wants to form a symbiotic relationship with (say) a plant, it sends out these little hormogonia cells to invade the plant. Like the spore-cells, these can then turn back into normal, undifferentiated cells.

I do think it's a pity that there isn't a course here purely for studying bacteria. On the other hand, it's probably better for me as a scientist to have a slightly greater range of knowledge beyond all things prokaryotic. Especially for the upcoming exams!

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Flores, E., & Herrero, A. (2009). Compartmentalized function through cell differentiation in filamentous cyanobacteria Nature Reviews Microbiology, 8 (1), 39-50 DOI: 10.1038/nrmicro2242