Figure 1: Bacteria under an electron microscope. Scale bar (red) is one micron, which is one thousandth of a millimeter. Orange arrow shows a bacterium that is about to divide (figure modified from Wikipedia).
We know that bacteria can make us unwell at times (causing diseases such as cholera, tuberculosis, pneumonia, leprosy, diphtheria, tetanus, ulcers, etc.), but they usually are considered rather exotic living entities either living in the sewer or somewhere in the thermal vents of the ocean – hence being envisioned as distant organisms. To most, they are the simplest life forms which are merely trying to make ends meet, struggling to survive and having little, if any, effect on the rest of life on earth.
All these are blatant misconceptions. Globally, 30% of the yearly oxygen on earth is produced by a certain “breed” of bacteria (footnote 1a). There are 1,000 different species of bacteria in and on a single human body, resulting in 10 times more bacterial cells than human cells (footnote 2). Correspondingly, there are a total of 1,000 times more bacterial genes in our body (footnote 3). Nevertheless, these bodily bacteria are not necessarily parasites, but are mostly beneficial. Primarily, they inhabit our digestive track and help us digest food that would otherwise go non-utilized, or produce various vitamins that we are unable to make ourselves (reference 1). The type and relative abundance of such intestinal bacteria is known to be linked to obesity (Figure 2). Last but not least, bacteria help our immune system to mature, thus helping us in being protected against their harmful kin (reference 4). Bacteria are not always random drifters: some can swim towards a food source (footnote 1b), while others (footnote 1c) can navigate their way towards the bottom of the ocean by sensing earth’s magnetic field (reference 5), where they can live better for they do not survive in atmospheric oxygen levels.
Figure 2: Mammalian intestine bacteria come primarily in two groups: Type B (footnote 1d) and Type F (footnote 1e). Recent studies (reference 2) indicate that the obese mouse (left), compared to its normal cousin (right), which has been fed an identical diet, has fewer Type B and more Type F bacteria. Similar patterns can be observed in humans: Type B bacteria increase (while Type F decrease) in obese individuals as they lose weight. The bacterial species that inhabit our body at birth may have significant consequences on our metabolism later in life, and can be the culprit, at least partially, behind various disorders, ranging from overeating to diabetes (figure adapted from reference 3).
In this article, I will try to further convince you that bacteria are more than “bags of enzymes” by elaborating on a mechanism that enables bacteria to carry out a “population census.” As we will see, this simplest social interaction helps an oceanic squid camouflage itself to hide from predators, as well as enabling pathogenic bacteria to evade the immune system before getting numerous enough to wage an effective war against the host.
A day in the life of an oceanic squid
The bobtail squid, which lives in the shallow coastal waters of the Pacific Ocean, is a nocturnal animal. That is, it buries itself under the sand in the daylight to sleep (Figure 3), and comes out at night to hunt and eat. In this habitat, a threat to life comes perhaps from a most unexpected source: The moonlight can penetrate the shallow waters, casting the squid’s shadow on the ocean floor to alert predators swimming above. Similarly, a predator swimming beneath can easily recognize the squid’s dark silhouette above the moonlit background.
Figure 3: Using its tentacles, the bobtail squid buries itself in the sand (A-D) during the daytime to sleep (figure modified from reference 6).
But fear not, because the squid is safe and sound thanks to an organ it harbors. Essentially, this organ produces light to counter-illuminate the shade on the seafloor (and similarly, when viewed from below, to match the amount of light coming from above) to make it invisible, like the stealth aircraft which can fly undetected amongst the radars. Furthermore, using a curtain-like structure that covers this light-producing organ, it can modulate the level of light it produces according to the intensity of the ambient moonlight which is detected by the receptors on the squid’s back.
This is undoubtedly one of the most amazing camouflage patterns, but how on earth does this little creature access light in the middle of nowhere to unfurl this “invisibility cloak”?
This is where bacteria come into play.
Bacteria’s way of conducting population census: Quorum sensing
A particular kind of bacteria (footnote 1f) inhabits the squid’s light organ. This is a much better place to live, as nutrients are more abundant compared to the otherwise planktonic life of the ocean. Within the body of the squid, the bacteria reach densities they can never be achieved in open waters.
The bacteria release small chemicals known as auto-inducers. As the name suggests, the auto-inducers can normally be detected by the very same bacteria, and consequently induce a series of biological events. However, when the bacteria are low in numbers, the auto-inducers float away after release without being detected. As the bacteria multiply in the squid’s light organ, reaching greater numbers, the external concentration of auto-inducers also increases as a function of the cell density. After a certain threshold concentration is reached, the auto-inducer is detected by (all) bacteria. This is how bacteria sense when the population has reached a quorum (footnote 4), hence “quorum sensing.”
When a quorum is reached in this fashion, a set of chemical reactions are triggered in each and every bacterium. Such biochemical reactions essentially resemble those which make fireflies glow. This process of light production by living organisms is known as “bioluminescence” (Figure 4). Therefore, after reaching a certain number in the squid’s light organ, the population of
Figure 4: Let there be light, and there was light. A) Satellite image of the bioluminescence across shores of the Indian Ocean, which is caused by another kind of light-generating marine bacteria. Such bacteria uses light to portray its otherwise unattractive home (that is ‘fecal pellets’), which is consumed by the marine organisms that end up in the animal’s nutrient rich gut. B) Glowing lab cultures of the squid’s bacteria that have reached high densities in the lab flasks (figures taken from references in 7). C) A potpourri of light-producing organisms. Bioluminescence is unique not only to the bobtail squid’s friendly inhabitant, but is rather a ubiquitous beneficial trait employed by many different organisms as a means of accessing food, attracting mates, or avoiding predators (figure modified from reference 8).
bacteria starts glowing, providing the squid with the light it needs to hide its silhouette from predators (Figure 5).
Figure 5: Auto-inducers (red dot, marked with a red arrow) released by the bacteria diffuse before being detected at a low bacterial cell density (left), hence creating no bioluminescence. At high bacterial cell density, the auto-inducers are detected by the bacteria, indicating that the critical density (or “quorum”) has been reached, and a cascade of biochemical reactions are triggered that lead to the bioluminescence of the population as a whole (figure modified from reference 6).
From an individual bacterium’s point of view, this is a very clever strategy if considered in terms of cost-benefit: Such light production through chemical means consumes a great deal of energy, hence is a costly transaction. Notwithstanding, a single bacterium will produce undetectable light levels alone. To this end, it is a “smart” move (footnote 5) for the bacteria to wait until the population reaches a “quorum” when a single bacterium will start making a difference. Then, the bacterium’s efforts to produce light will not go unnoticed.
As a matter of fact, the light organ of the squid is not just a nesting place for bacteria, but is also equipped with light-sensing capabilities. It was recently discovered that the squid can identify and then reject a (cheater) all-time non-luminous mutant strain of bacteria from its light organ (reference 8) via such a detection capability.
The mutual benefit between the bacteria and the squid occurs in cycles that overlap within a 24-hour routine. In the daytime, as the squid hides itself for sleeping (hence cannot feed the high population of bacteria anymore), it releases 95% of the bacteria into the open waters. The cycle is thus reset: The diluted bacteria starts growing from low numbers in the non-glowing state. By approximately the time the bacteria has multiplied enough to reach a glowing density, the squid wakes up and comes out to feed (Figure 6).
Figure 6: The daily cycle of the squid-bacteria interaction. The blue curve indicates the number of bacteria (marked as “bacterial population level”) which the squid houses in its light organ. Starting from low numbers during the sleeping period of the squid, bacteria gradually grows to reach the “quorum” level at which it starts to glow. Around sunrise, the squid buries itself, releasing 95% of the bacteria: this is indicated by a sudden drop in the blue curve. This cycle happens repetitively with a 24-hours period (figure modified from reference 6).
Quorum sensing as a social trait
The phenomenon of quorum sensing, discovered by Bonnie Bassler, currently a professor at Princeton University, is not specific to the bacteria of the bobtail squid, but is a ubiquitous feature that enables almost all kinds of bacteria to carry out feats of multi-cellular life. Collectively, they can accomplish what they cannot when they are alone. Analogous to different languages, different bacteria have different auto-inducers that they use to communicate with each other (intra-species communication). On the other hand, different bacterial species can also communicate with one another (inter-species communication) via a common auto-inducer; which is essentially the “Esperanto” of bacterial communication.
One opportunistic type of bacteria (footnote 1g) which can cause diseases in animals and humans uses quorum sensing, but not to help others. These bacteria grow and multiply in the host without harming it until they reach to a certain concentration. It is only when they become numerous enough, which is once again determined via quorum sensing, to overcome the immune system of the host that they release the virulence factors that lead to disease (reference 6).
On the other side of the coin, medical researchers are looking for ways to disrupt the quorum-sensing mechanisms of pathogenic bacteria to render them ineffective by making them “mute and deaf.” While synthetic therapeutic molecules are currently being investigated, recent findings indicate that garlic locks quorum-sensing in the aforementioned bacteria (reference 9) providing promise for clinical applications.
“The most incomprehensible thing about the universe is that it is comprehensible.”
Although most living systems currently appear to be very complex, it is neither the “complexity” nor the “mysteries” of life, but rather our (ever-deepening) knowledge that should make one believe in the Sustainer of all life. The flaws in “God of gaps” fallacy were outlined in the recent The Fountain article “Natural is Nothing Less than Miraculous,” based on an interview (reference 10) with Dr. Denis Alexander of Cambridge University, UK:
“I think the idea of the God of the gaps is a very unfortunate idea; that has a very long history. Actually, it goes back many centuries. I’m not quite sure when the idea first began. But I think it’s always been tempting as science got going, especially in the nineteenth century when science was less developed than it was now. It was a temptation for people to try and locate their God within the present gaps of the scientific knowledge. So obviously, as the gaps are closed, so one’s understanding of God will shrink. God is then located in smaller and smaller mysteries.
“So whether we have current gaps in our knowledge now has no theological significance as far as I’m concerned. It doesn’t matter. It’s of no particular interest, so theology has no hidden investments in gaps in our knowledge. It really doesn’t matter. It simply says we’re ignorant about many things.”
As simple as they may seem, bacteria execute daunting tasks: They may be friendly inhabitants as well as harmful foes. Despite being envisioned mostly as “loners,” bacteria can exhibit the basic features of social interactions and collective behavior. More intriguingly, all such tasks are carried out with a limited number of genes within a minuscule body.
How do we define life? What attributes are entitled with the process of “living”? What is the minimum number of genes that can constitute a living organism? What aspects discriminate bacteria from being a simple “bag of enzymes”? Although we simply do not yet know the answers, it seems as if scientists will continue to eavesdrop on bacteria; the revelation of many amazing mysteries is just around the corner.
After all, bacteria are no small matter.
1) The following are technical terms for further reference: (a) cyanobacteria (b) chemotaxis (c) magnetotactic bacteria (d) Bacteroidetes (e) Firmicute (f) Vibrio fisheri (g) Pseudomonas aeruginosa
2) At first glimpse therefore it sounds like we are a ‘super-organism’ that consists of multiple species, but since the volume of bacteria is 1/1000 of our own cells, we are still 99% human in mass.
3) In total, there are approximately 20 million different bacterial genes in the body of a single human, outnumbering the 20 thousand-some genes within the human genome by a factor of 1,000.
4) According to “thefreedictionary.com,” the literal definition of the word quorum is: “The minimal number of officers and members of a committee or organization, usually a majority, who must be present for valid transaction of business.”
5) Similar language is used throughout the text merely as a figure of speech. The bacteria is not even close to being ‘intelligent’ enough to plot any strategy whatsoever, but rather have been equipped with capabilities to develop such means by the Creator of all things. Furthermore, establishing explicit links as such is purposefully refrained from in the article so as not to constrain thinking or limit the imagination of the reader.
1. “It’s me, Peter, your intestine!” Irfan Yilmaz, The Fountain Magazine, 2008
2. i) “An obesity-associated gut microbiome with increased capacity for energy harvest.”. Turnbaugh and others, Nature, 2006. ii) "Microbial ecology: Human gut microbes associated with obesity.", Ley and others, Nature, 2006
4. “Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity.”, Clarke and others, Nature Medicine, 2010
5. “The Tiniest Captains of the Ocean.”, Ahmet Uysal, The Fountain Magazine, March-April 2010
6. “Shedding Light on an Invisible World.” Bonnie Bassler, HHMI, Holiday Lectures on Science, 2009
8. “Bioluminescence in the Ocean: Origins of Biological, Chemical and Ecological Diversity.”, E. Widder, Science, 2010
9. “Garlic blocks quorum sensing and promotes rapid clearing of pulmonary rudomonas aeruginosa infections.”, Bjarnsholt and others, Microbiology, 2005
10. "Natural is Nothing less than Miraculous." Interview with Denis Alexander by Mustafa Tabanli, The Fountain Magazine, May-June 2010.