A simple GIF to give a look at the complexity of a 1000-ring circus going on in cells all the time. Each ‘ring’ is a different pathway necessary for this generic microbe to survive. Wish I had 40 years to make an accurate depiction of an actual bacterial circus with its 2000 ‘rings’. Enjoy!
Time again for My Tiny Highlight (MyTH) of a particular bacterium. This week is the infamous Pseudomonas aeruginosa. This trooper can be found almost anywhere on earth due to its ability to use all kinds of material as food including diesel and jet fuel. Most of us know it as a common infection you get while in the hospital because it is so darn hard to kill. If you know someone that suffers from cystic fibrosis, this bacterium can be fatal as it is commonly found in the lungs of these patients causing pneumonia. I personally learned about this bacterium in school when talking about hot tubs due to its resistance to disinfectants.
P. aeruginosa is one of the most famous microbes for forming biofilms. A biofilm is a group of cells that attach to each other and to some surface usually by secretion of sticky sugars from the cells. A common sticky sugar, or exopolysaccharide (EPS), excreted by P. aeruginosa is alginate, an uncommon sugar for bacteria since it is most commonly found associated with brown algae. Its existence in Pseudomonas has led to significant knowledge about the synthesis of alginate (alginate biosynthesis; another ring in the bacterial circus). This knowledge is leading to novel medical applications for alginate.
P. aeruginosa is also known for its role in a multicellular behavior which seems strange for a single-celled organism but is becoming more and more common. Quorum sensing was first described over 40 years ago. I beg you to check out Bonnie Bassler‘s TED talk about this. QS is how single cell bacteria are able to send signals into the environment to communicate with members of their own species and with other types of bacteria as a way to assess their population.
Another feature of P. aeruginosa is their modes of transportation, i.e. motility. P. aeruginosa has two major modes of getting around their environment, swimming motility with flagella or “twitching motility” on a surface using Type IV pili. We have discussed flagellar motility before (Chemotaxis). Type IV pili (TFP) is different. Pili are somewhat similar to flagella because they protrude out of the cell and are used to move around. Unlike flagella, pili don’t rotate but rather extend out before retracting back to the cell pulling the cell in the direction of the pili tip. The coordination of pili extension and retraction is guided by a chemotaxis-like pathway. Many bacteria have evolved to use chemotaxis proteins that have adapted to new roles within the cell.
I will end this MyTH with a special shout out to one of my favorite researchers, Carrie Harwood. Caroline Harwood is a professor at the University of Washington in Seattle. Carrie’s daughter suffers from cystic fibrosis and this led to Carrie’s curiosity in P. aeruginosa. She is a pioneer and a role model for many female scientists including Becky Parales. For her tireless career, Carrie was inducted into the National Academy of Science a few years back. A recognition well deserved.
My family and I recently went to a circus. It had one ring, and that was manageable. We have also been to a traditional three ring circus in the past. Personally, I felt there was too much going on at one time to enjoy all three rings at once. Each ring had skillfully trained performers doing their job for the enjoyment of the audience simultaneously. That is how a circus functions. Now imagine if you were able to observe a circus with more than 1000 rings. Imagine the complexity and the majestic choreography unfolding before your eyes. This is essentially what bacteria have been doing f0r millions of years with ease Instead of rings, these little circuses have pathways, a group of proteins/enzymes that all function together to perform a task. Like a circus, these pathways are not in isolation but instead many are performing at the same time. Even the “simplest” bacteria have over 500 pathways. Imagine trying to watch a 500 ring circus and understanding what is going on or being in charge of all 500 rings as they perform. Just because we don’t understand microbes does not make them simple, it makes us naive.
When sequencing a bacterial genome, computers and researchers try to connect all the dots. That is, they try to predict the role each gene/protein plays within that circus. For a bacterial circus with 5000 members (genes), only about one third of those can be assigned to a particular ring (pathway). This means a majority of members from a genome have a role we haven’t observe enough to classify its context. Now, imagine two thirds of KNOWN genes in KNOWN bacteria and the fact we approximately know 1% (or less) of the total number of bacterial species on, or in or above, earth. It doesn’t take long to discover that there is much more to discover in microbiology.
We as humans are beginning to utilize bacteria, or their pathways, to advance our civilization. Whether it is to clean up our polluted, toxic land or to advance medicine through fecal transplants, bacteria will play a much bigger role in the near future. Not bad for such small species. 500 rings or 2000 rings, these circuses are truly the greatest shows on earth!
Time for Part 3 in the series examining how bacteria make decisions. Parts 1 and 2 focused on chemotaxis. Today, we will focus on how bacteria decide which genes need to be expressed and which need to be repressed. One of the most prevalent ways a bacterium decides this is by using a two component system, or TCS. TCSs are relatively simple compared to chemotaxis. As you would suspect from the name, TCSs are pathways consisting of only two protein members, the sensor histidine kinase and the response regulator. Histidine kinases are a major protein family in bacteria because they are able to sense many different factors in the bacterium’s environment including nutrients, toxins, fellow bacteria, etc. In case you are wondering, chemotaxis is a modified form of a TCS in which the histidine kinase CheA is regulated by the activity of a separate protein, the methyl-accepting chemotaxis protein.
What if you are a bacterium and you have been using a certain type of carbon source to generate energy and suddenly that carbon source isn’t as prevalent? In this case, you would want to shut down the enzyme factories that were converting the previous food source into energy and begin preparing new enzyme factories to convert other food sources into energy as you prepare for starvation. If these conditions persist, you might want to decide to hibernate in the form of a spore or cyst until conditions around you improve. Or, if other food sources are sensed in the environment, any special enzymes that would be needed to convert them into energy would need to be synthesized from their respective genes. All of these scenarios are controlled by TCSs. The conditions are used as input for the cell to decide the best strategy to survive and thrive. Histidine kinase activation leads to a hand-off event from the kinase to the response regulator of a molecule which acts as a green light for the response regulator to proceed with its job. This job may be to turn on gene expression to produce proteins needed in the cell. The response regulator’s job may be to shut down gene expression for proteins no longer needed by the cell. It is a carefully orchestrated balancing act evolved over millions of years to make sure only the proteins/enzymes needed by the cell at a given time are present assuring highly valuable energy molecules are not wasted.
Yet another way bacteria are Nature’s smallest 5000 ring circus.
In order to determine the ~99% of bacteria in the environment we do not know about, one approach to overcome this challenge is called metagenomics. The above (amateur) animation tries to illustrate the technique. One area where metagenomics is useful is contaminated land that is unhealthy for human dwelling. However, underneath our feet are untold and unknown bacteria communities that are utilizing the very same toxic material to grow and thrive. Metagenomics is one approach that can help us understand 1) what bacteria are there and 2) how in the world are they able to use this material. This is only the beginning of the metagenomic revolution that will someday (soon) add fuel to the synthetic biology revolution to create super bacteria that can alert us of potential toxic exposure and then begin the cleanup process.
Welcome to the world of Science (not Science Fiction)!