Field of Science

Multicellular bacteria

ResearchBlogging.orgPart 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!


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


cuco3 said...

It's always seemed to me that anything that can evolve will do. So what stops these multicellular bacteria from taking it further? Presumably something does.

Are there more restrictions, or is it simply that bacteria are so well adapted that there's just no need? Or have they missed the boat? Are the multi-cellular niches already taken?

Lab Rat said...

There are restrictions, the biggest one is in nuclear size. Multicellularity requires differentiation, which means that you need a different set of genes for each cell type, in the bacteria shown above every cell contains all the genes to become any type (heterocyst or spore or whatever) but supresses the ones it doesn't need. This makes a far bigger overall number of genes, and a large number that will never be expressed.

There is only so big a genome can get before it starts needing to be packaged up in a nucleus (to stop it getting degraded and to keep it out the way of the rest of the cell). You also need far more organised systems for processing transcripts, which again work better when the nucleus is in its own compartment (i.e transcript processing, and epigenetic histone control seen in eukaryotes).

Gene size does restrict multicellularity. But I would say bacteria have managed to take over pretty much every niche there is without it.

Lucas Brouwers said...

Really cool post!

On a related note on restrictions: not only do multicellular bacteria need a 'double set' of genes, the number of transcriptional regulators also needs to increase. Some studies indicate that the number of regulators scales quadratically with the total gene number, so the limit for prokaryotic complexity might come from this increasing demand of 'overhead' (which again ultimately comes down to genome size as you explained!). See for example.

"large multicellular bacterial 'animals' roaming the plains" --> evolutionary speaking, that would be us, right ;)?

Lab Rat said...

Thanks for the links Lucas! And yes, multicellularity does require all sorts of factors which ultimately increase the genome beyond managable size for the far smaller prokaryote cell.

""large multicellular bacterial 'animals' roaming the plains" --> evolutionary speaking, that would be us, right ;)?"

Not unless you're a prokaryote! As far as I was aware your cells did have nuclei, although I suppose that on the internet, noone knows if you're a bacteria... :p

cuco3 said...

Thanks for the further explanations.

Aren't we just machines for carrying bacteria around? :-)

ncm said...

Yes, distinguishing "us" from bacteria is like distinguishing Polynesians from Africans. We're *all* of us Africans if you go back a little way.

Lab Rat said...

Haha, yes. To bacteria we're just enormous multicellular bodies providing food, nourishment and exciting evolutionary challenges.

There is a difference in years of several orders of magnitude (and a difference in Species, Kingdom, Super-kingdom etc...) but certainly both people and bacteria came from the same little proto-prokaryotic blobs.

Lucas Brouwers said...

@Lab Rat @ncm That was the evolutionary relationship I was (too) subtly hinting at in my original comment. I'm glad it got sorted out without my intervention :P.

Mason Posner said...

Is multicellularity a presence/absence state? Where do you draw the line between cooperative behavior between cells (quite common in bacteria?) and "multicellularity". Speaking from an animal perspective, is there a significant difference between "multicelluar" sponges and protistan choanoflagellates? The latter contain the fundamental animal signaling molecules that were later leveraged for greater cell-to-cell coordination.

Thanks for the great posts.

Lab Rat said...

I would define multicellularity as an aggregate of cells that can communicate with each other, and depend on each other for survival; thus bacterial colonies and sponges are not multicellular (as sponges can be mashed up and repatriated and still grow fine) whereas the bacteria in this post are.

I realise that this is a purely arbitrary definition though, and many spongologists might disagree! Also, I've just realised that your comment implies sponges *can* intercellularly communicate. Which I didn't know, and will have to look up if I have time.

Thanks for your comments and support.

radu_addmall said...

Some examples of the numerous life forms living on our body made visible by scanning electron microscopes. Excerpt from the documentary "The invisible world"


CyPhy said...

I enjoy your blog and have lurked here for a while. You have written broadly on many microbial topics, and I was fascinated to see that you have written about multi-cellular bacteria. You have a great mind for microbiology, and I hope you will take the time to now write something about acellular bacteria, that is, so called "l-forms" or cell-wall deficient bacteria. L-forms will be the hot topic of the 21st century in medicine, and it would be wonderful to see a great mind like yours get in on the ground floor!

Lab Rat said...

@radu: Thanks for the link! Looks really interesting.

@CyPhy: Thanks so much! I took a brief look at lab generated L-form bacteria back in August:
I haven't actually read much about them since then, so might go back and revisit for another blog post. It would be very interesting to cover L-forms found outside the lab, within a clinical environment.