How do bacteria make decisions? Part 5: Mystery of a mysterious kind

animated cyclic-di-GMP gif, second messenger gif
110 different confirmations of cyclic-di-GMP

In Part 4, we looked at the relatively recent discovery of the bacterial second messenger molecule cyclic-di-GMP. The decisions bacteria make weigh heavily on the amount of this molecule found within the cell. However, how a bacterial cell knows how much c-di-GMP there is ultimately remains a mystery. The focus of early research involved finding what regulated the synthesis and degradation of c-di-GMP. Thus, the majority of publications in print focus on the enzymes that perform these functions, GGDEFs and EALs. Also, by deleting certain GGDEFs or EALs from a bacterium, scientists were able to determine what effect this change would have on the cell’s decision making and lifestyle. Most research was performed in medically relevant species like Vibrio and Pseudomonas. This short-sighted focus has led to a distinct role of c-di-GMP in the cell that may not be absolute. I digress…

A cell produces c-di-GMP in response to some environmental signal. Now what?

Great question; one that is still not answered. Various proteins have been shown to interact with or bind c-di-GMP including the PilZ domain. The list of c-di-GMP effectors has grown slightly over the past few years to include examples of transcriptional regulators in both Vibrio and Pseudomonas (VpsT and FleQ, respectively). Transcriptional regulators are proteins that help carry out the decisions made by a cell by regulating gene transcription. However, these are only two examples from two bacteria. What about the vast number of other bacteria out there? How do they “see” c-di-GMP? Cyclic-di-GMP is a vital component to bacterial decision making even though our knowledge of how it is seen by a cell is a huge unknown.

My hypotheses and speculations (with some evidence)

In the last chapter of my dissertation (under embargo), I investigated what other protein domains could potentially bind c-di-GMP bioinformatically. Using my methods, I could predict proteins in the nonredundant database that could potentially bind c-di-GMP. One group of proteins I found were those already shown to bind other nucleotides like ATP. I was able to test my method against a publication that biochemistry and proteomics to identify c-di-GMP binding proteins from Pseudomonas. This crude “chemical proteomic” approach identified around 200 potential binding proteins of which the method I created also found several of the same proteins without the exhaustive time and effort of “wet bench” experiments.

This is not a post about how good I am at science. This is a post about using new and different methods to answer questions within science not unlike the investigation that identified the PilZ domain as the c-di-GMP binding protein in the first place. Unfortunately, my time in the lab was over before I could test my hypotheses, but my curiosity and passion live on. I will say that I predict receiver domains are very common c-di-GMP binding effectors that will be the next major discovery in this elusive mystery of how cells use c-di-GMP to make decisions.

Animated Glycolysis GIF

animated glycolysis gif, animated biochemistry gif

Hexokinase, Phosphoglucose Isomerase, Phosphofructokinase (PFK), Fructose 1,6-bisphosphate aldolase, Triose Phosphate IsomeraseGlyceraldehyde-3-Phosphate DehydrogenasePhosphoglycerate KinasePhosphoglycerate Mutase, Enolase, and Pyruvate Kinase.

The protein structure at the top below the plasma membrane (blue) is the cytoplasmic portion of Mannose PTS permease that transports glucose into the cell. In the animation, glucose enters the cell and is converted down the glycolytic enzyme path into the correct product structures until ultimately 2 molecules of pyruvate are produced for processing within another cellular pathway.

Related articles

Animated bacteria GIF: What lies within? Glycolysis edition

animated bacteria GIF, microbiology, bacteria gif, animated gif
Glycolysis, the first pathway of sugar metabolism, is what lies within this series

Animated bacteria GIF: What lies within

animated bacteria GIF, microbiology


In case you haven’t noticed, since discovering how to make animated GIFs a couple weeks ago, I can’t stop. This one is a simple reminder that bacteria may be small, but if you look close enough, you will find just how complex they can be.

Animated GIF: Bacteria swimming

animated GIF bacteria, animated GIF, microbiology
Azospirillum brasilense cells swimming in an oxygen gradient. Magnified 40X

I’ve spoke a lot lately about bacterial chemotaxis. I wanted to give you a taste of the real deal. These cells are happily navigating the medium with many swimming in circles, a phenotype of Azospirillum brasilense cells prior to cell aggregation (grouped cells).



Qi, X. et al. Swimming motility plays a key role in the stochastic dynamics of cell clumping. (2013) Physical Biology 10: 026005. Link

Bible, AN., Russell, MH., Alexandre, G. The Azospirillum brasilense Che1 chemotaxis pathway controls swimming velocity, which affects transient cell-to-cell clumping. (2012) Journal of Bacteriology 194: 3343. Link

How old are you? (The answer is not what you think)

My 4 year old daughter can tell you how old she is even though her concept of time is essentially nonexistent. She can’t wait to be “big”, which in her mind is 5 years old. However, the rest of us are not much better at answering the question about how old we are. Yes, we are correct about our legally recognized age, but we are way off on our natural age.

We’re all the same age…really old

Atomic level

Since everything is made up of matter, we all consist of atoms. These atoms all come together to make us who we are, but my daughters atoms are not 4 years old or even 4 billion years old. At some point shortly after the big bang, atoms came together thus forming the different elements (think periodic chart). Here we are 13.7 billion years later; all of us made of the same elements. This makes me shake my head when I think of nations going to war. We’re all made of the same elements, same matter. It doesn’t seem natural. With this argument, we are all really old at about 13.7 billion years old.

We’re all about the same age…really young

Cellular level

Humans consist of around 10 trillion human cells (excluding the 100 trillion microbial cells). These cells have a turnover rate that suggests each human consists of entirely different cells every 7 years. With this argument, we are all pretty young with no one older than 7 years old.

We’re all rentals…really short-lived

Since we’re all made up of the same atoms and these atoms have essentially been around forever, they have been used by other matter before us. And, most certainly, they will be used by matter long after we as humans are gone. Mother Nature sees us as atomic renters, but definitely not rent-to-own.

We’re all tenants…really big compared to our landlords

Something else I have been thinking about for a while now; almost everything we see or touch is completely covered with a thin layer of life, i.e. bacteria. They cover us. They cover our loved ones. They cover our…everything! Also, they have been around a lot longer than we have as species. We are just using the same space they are. Heck, we are a space they live! So, in this sense, they are allowing us to use this space as tenants. They are very nice landlords, too. Consider all the benefits we receive from their generosity (think microbiome).