The view from the bottom of a microbial pig-pile

If you look outside your window, what do you see?

Most likely, you will notice a lot of life out there. Based on this observation alone, you may agree with me that 'survival of the most resourceful' might be better to describe what is going on out there. A diverse array of organisms are fighting for survival, but persist through utilizing clever strategies.

These clever strategies are what draw us in to marvel at nature's ability to make lemonade out of lemons. For example, plants have some remarkable abilities to deal with changing conditions to overcome being stationary. 'Mutualism of the month' posts highlight the sometimes unusual resourcefulness of organisms that team-up to survive. 'Sex is weird' points out that nature, often unshamefully, will always find a way to reproduce. And, what's the deal with fungus? Alena pointed out recently how wild and alien fungi seem given their uniqueness. Taken together, no one strategy is better than the others since all these organisms are surviving outside your window.

The truth is, it is crowded out there.

The fact that real life is crowded is something scientists and biologists wrestle with all the time. We like simple models and laws that can be used to explain and predict the natural world. However, finding a 'one size fits all' solution to nature’s problems or a general theory that will explain how the vast diversity of life behaves can be a challenge. In fact, it may even be impossible.

Is it possible to find a general theory of community ecology? The debate rages on. Image credit: Stephan van Es via flickr.

Is it possible to find a general theory of community ecology? The debate rages on. Image credit: Stephan van Es via flickr.

Most microbes live in dense communities known as biofilms; biofilms that you likely come in contact with on a routine basis. The thin slime that covers your teeth after you haven't brushed for awhile (plaque) and the slippery slimy coating of rocks on the bottom of a river are common examples of biofilms. These slimes are actually rich, dense mixtures of microbes growing in close quarters with one another. Given the prevalence of crowding, we need to study how microbes behave under crowded conditions to culture them in the lab and understand how they adapt.

Recently, Dr. Foster's group at the University of Oxford published a paper on the importance of positioning in microbial evolution. The study is based around the curious observation of how one strain of bacteria called Pseudomonas fluorescens Pf-01 grows on agar plates.

The microbiologist's solution for a crowded culture

Imagine I give you a bucket of sand and I ask you to pull out individual grains that represent the various types of rock present. You could try sifting through with your bare hands, but that could be time-consuming and inefficient. Besides, there might be unique grains on the bottom of the bucket. One solution is to mix up the bucket to make it homogenous, take a handful and dash it out across a surface like a desk. Although a bit messy, now you have spread the grains out from one another you should be able to find unique pieces more easily. Microbiologists utilize this same strategy with microbial samples and spread bacteria over the surface of a solid gel to isolate individuals from a typically very large number. The difference is that when individual microbial cells land on the surface of these plates, they do not just sit there. If you let the plate sit out long enough, the microscopic will become macroscopic; a single cell grows and divides creating a microbial pig-pile called a colony that you can see without a microscope.

A photograph of colonies on the surface of an agar plate. In theory, each colony is founded by a single bacterial cell that landed on the plate. Microbiologists often use this strategy  to isolate bacteria and examine diversity in samples if the bacteria are culturable. Image credit: Kenneth Flynn.

A photograph of colonies on the surface of an agar plate. In theory, each colony is founded by a single bacterial cell that landed on the plate. Microbiologists often use this strategy  to isolate bacteria and examine diversity in samples if the bacteria are culturable. Image credit: Kenneth Flynn.

Dr. Foster's group noticed something a bit unusual when they plated their bacteria (Pf-01). Every once in a while, colonies would have slimy growths jutting out from them. Isolation of the cells that belonged in these extra slimy portions revealed that these cells had actually mutated to overproduce and secrete this molecule called alginate. The question is, why some of the cells evolve this unusual behavior?

To answer this question, you need to think like a microbe.

What is life like in a microbial pig-pile? In a word, crowded. I am not sure if you have ever been at the bottom of a pig-pile before but sometimes it can be hard to breathe. The microbes at the bottom of this colony are oxygen-starved by the microbes piled on top. To overcome this problem, some of the microbes acquired a mutation that caused a polymer production pathway to likely become unregulated and this excess polymer similar to a molecule called succinoglycan pushes these cells to the top of the pile. All at once, these cells gain access to the oxygen they need and drown their competitors in the process.

Pseudomonas fluorescens Pf-01 colonies on a plate left out for several days will typically develop these 'blebs' or protrusion of cells that overproduce a molecule called alginate. This production pushes these cells to the surface of the colony to gain access to oxygen they need. Image credit: Figure 1A from Kim et al., 2014 published in PNAS.

Pseudomonas fluorescens Pf-01 colonies on a plate left out for several days will typically develop these 'blebs' or protrusion of cells that overproduce a molecule called alginate. This production pushes these cells to the surface of the colony to gain access to oxygen they need. Image credit: Figure 1A from Kim et al., 2014 published in PNAS.

Perhaps the most intriguing part about this research is that polymer-overproducing strains are commonly observed during chronic infections of persons with cystic fibrosis. Commonly, it is thought these strains evolve polymer-overproduction to protect themselves from the immune response during these infections. However, here this phenomenon happens just on the surface of a gel. For me, only one burning question remains:

Are the microbes in these infections adapting to us or each other?

If you attended a concert in Europe or the United States, how much would your priorities during the concert change? Sure, the people may talk differently but you still want good seats near the stage with a constant flow of carbonated beverages. Most of your experience will be centered around battling the crowds of other people attending. Perhaps, microbes experience infections in a similar way. Although the venue changes, a microbe may primarily have to deal with your close neighbors in a crowded space and predicting adaptation during chronic infections may require us to think about what the world looks like to these microbes.