Before I get started with this conundrum, I must admit that I am somewhat biased toward the prokaryotic domain that is the Bacteria. All of us know about elephants and salmon and eagles and a giant variety of all the multicellular organisms on Earth (largely due to how large and visible they are, I would say), but how many of us know more than three bacterial species? Most might have heard of Salmonella enterica and Escherichia coli, given their almost universal presence in children's textbooks and the rampage that is diarrhoea, and a few more will even know of the sly troublemaker Streptococcus pneumoniae (strep throat sucks). But what of helpful genera like Streptomyces, which are used in pharmaceuticals to produce over two thirds of all naturally derived antibiotics? Or the prettifying, sea-borne pacifists known as Vibrio fischeri?
As a biochemist, I may surprise you when I say that much of my work and research revolves around microbes. There are other occasional model organisms, like worms, fruit flies (mighty paragons of evolution) and lab mice, but our laboratory practicals mostly tend to operate with swimming unicellular blobs (bacteria, for instance). This makes sense for three reasons: first, the general public are not keen about scientists experimenting on little kids and such (yep, makes sense); second, bacteria are very easy to manipulate; and, third, there are billions of the little critters literally everywhere you look. Touch your left armpit - bam! Suddenly, you have three billion or so more copies of skin microbes on your index finger (partly a joke, but if you've not washed recently then you've got a surprise waiting for you!).
This means that it is a pretty good idea to educate yourself about whatever things these microscopic things do. And, so, to start what will most likely be an ongoing series of posts that concern bacteria, this time I will be writing about how they communicate with each other.
Quorum Sensing & Squids
When I first heard of the phrase 'quorum sensing,' I must admit that I did not have a clue about what meant. Therefore, though this blog isn't really about semantics, here is an exact definition taken from the Cambridge Dictionary: "the smallest number of people needed to be present at a meeting before it can officially begin and before official decisions can be taken." We don't really wanna talk about people, of course (ugh!). Indeed, biologically, 'quorum sensing' basically refers to when a group of microorganisms are trying to 'sense' if the group contains the minimum number of individuals that exceeds a certain threshold.
I already mentioned the species Vibrio fischeri, so let me use them as an example. In the middle of the Pacific Ocean, living in shallow coastal waters next to the Hawaiian Islands, lives a vibrant creature known to most as the Hawaiian bobtail squid - and to overzealous zoologists as the Euprymna scolopes. This animal is mainly active at night and, living in an area with minimal light pollution from human civilisation, is subject to the luminous stars in the sky and reflected light from the moon. It is also rather small, and so must develop a way to camouflage itself from meandering predators. Here is where the bacteria come in.
Living in symbiosis in a mutualistic relationship (where both species involved gain from it) with the Hawaiian bobtail squid, V. fisheri makes its home in the squid's light organ, situated next to its eyes and facing the seafloor. To prevent forming a shadow underneath and promoting its presence to other sea creatures, the squid uses the bioluminescent V. fischeri population to produce light that mimics natural cosmic illumination, thereby reflecting it off the walls in its light organ and out of a cavity to end up shining downwards. The intensity of the light, as well as how open the cavity is, depends on the time of day. In return for the service, the bacteria receive shelter and sustenance from their host.
I should stress that this seemingly one-faced relationship is so important to the squid that - according to a group of researchers led by Dr Silvia Moriano-Gutierrez at the Pacific Biosciences Research Centre - gene expression involved in the process only occurs when light-producing bacteria (i.e. V. fischeri) are present in the organ, stopping almost entirely otherwise. This is rather fascinating, as it shows that the squid is unconsciously able to tell when light is being produced by symbionts in its light organ or not, and is thereby able to decide when energy is needed to maintain that relationship. Which, in normal circumstances, is always.
Anyway. These bacteria are not always luminescent; in fact, whenever scientists observe them outside the Hawaiian bobtail squid in the wild, they are as dark as they are small (a.k.a. very). Somehow, V. fischeri is capable of emitting light only when they gain anything from it - inside a squid - preserving the energy when they don't. How do they do this? Via quorum sensing, of course! Haha.
To communicate with each other, bacteria have evolved over the millennia to release small chemical pheromones called autoinducers, which can range from small proteins (peptides) to smaller hydrophobic molecules. In regards to V. fischeri, they release the latter, and the type they release has the slightly convoluted name of N-acyl homoserine lactone (AHL for short). They emit this chemical pretty much always. When in small populations, AHL molecules simply drift off into the surroundings, rarely coming into contact with other members of the population; when the bacterial density increases, however, something interesting happens.
All of a sudden, the AHL being produced starts entering neighbouring cells at a rate that is sufficiently high to influence the genes inside them - genes that are involved in producing AHL get up-regulated to form a positive feedback loop, for instance. Basically, this results in more AHL being made and released more quickly, which causes more of it to enter cells that then become affected by it and start creating more AHL, etc. Think of it as a backyard party between all the people in the neighbourhood - though quiet at the start, the more people come the louder and rowdier it gets, all the way till the house starts shining like a disco ball on steroids. The squid likes it, at least. (Perhaps we could also use this threshold-searching behaviour to design the biotechnological equivalent of diode circuits, or something? There's potential here, I think.)
In larger quantities, AHL also makes V. fischeri luminesce. This occurs because the proteins that AHL operates on in the bacteria cause a particular row of multiple genes in their DNA (called an operon) to be expressed, simultaneously causing the aforementioned feedback loop and also producing bioluminescence-inducing Lux proteins to be made. In turn, through a complex cycle of enzymatic reactions, V. fischeri bacteria produce high-energy molecules that spontaneously flouresce to emit light. Since the population is nourished and inevitably larger inside the light organ of Hawaiian bobtail squids, we can see how the whole cycle plays out. Life is not an isolated event, after all, but a ping-pong game between the trillions of organisms on the planet (most of them microbes!).
Here's another, perhaps more frightening, example: Staphylococcus aureus. These utilise peptide autoinducers to communicate with each other, but I would liken the process more to rallying an army than gathering party-goers. You see, S. aureus is a pathogenic type of bacterium, responsible for nasty complications like pneumonia and lung disease, but it only starts its warmongering when inside an unfortunate human host. When it has infected them, the bacteria spreads autoinducing peptides (AIPs) that have similar effects to the ones described with AHL. Instead of directly entering the cells, though, it attaches to them on the outside to make other internal peptides do the magic - which doesn't cause bioluminescence, but triggers the biochemical pathways in S. aureus that make it release virulent toxins and in general act like a very big ass. Still, interesting stuff!
I could give you a few more instances of where quorum sensing occurs, but it would probably get repetitive with all the chemical names and pheromones and whatnot, so I'll stop there. There is a mind-bogglingly endless expanse of this stuff, though, so hopefully you can see how bizarre and outright clever the invisible part of nature can get. No wonder humans spend so much time studying little blobs in the lab - they are the veritable keys to life.
- Watve, M. G. et al (2001). How many antibiotics are produced by the genus Streptomyces? Arch Microbiol 176(5), 386-90. Retrieved from https://link.springer.com/article/10.1007/s002030100345
- Grabowski, M. (March, 2020). Glowing bacteria in Hawaiian bobtail squid affect its eyes from afar. University of Hawai'i. Retrieved from https://www.soest.hawaii.edu/soestwp/announce/news/glowing-bacteria-in-hawaiian-bobtail-squid-affect-its-eyes-from-afar/
- Prescott, R. D. & Decho, A. W. (January 2020). Flexibility and Adaptability of Quorum Sensing in Nature. Trends Microbiol 28(6), 436-444. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S0966842X19303191
- Frazee, C. and McFall-Ngai, M. (2014). The Hawaiian bobtail squid is an established model system for the study of the colonization of epithelia by bacterial symbionts. PLoS Biology Issue Image, 12(2), ev12.i02. Retrieved from https://journals.plos.org/plosbiology/issue?id=10.1371/issue.pbio.v12.i02
- Studer, S. V. et al (August 2014). Non-native acylated homoserine lactones reveal that LuxIR quorum sensing promotes symbiont stability. Environ Microbiol 16(8), 2623-2634. Retrieved from https://sfamjournals.onlinelibrary.wiley.com/doi/abs/10.1111/1462-2920.12322
- Cunningham, A. B., Lennox, J. E., and Ross, R. J. (2010). Quorum sensing and cell/cell signaling in bacteria. The Biofilms Hypertextbook. Retrieved from http://www.hypertextbookshop.com/biofilmbook/v004/r003/contents/chapters/chapter002/section006/blue/page001.html
- Rutherford, S. T. and Bassler, B. L. (2012). Bacteria quorum sensing: Its role in virulence and possibilities for control. Cold Spring Harbor Perspectives in Medicine, 2, a012427. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543102/