Patrons: metabolites/compounds/substrates and products
Managers: two-component proteins to regulate gene transcription
Employee list: genome
Copy machine: DNA replication machinery
So, in the last part our restaurant was going great and we opened up a new restaurant with the same employee list among other things. The two restaurants are now independent of each other and are free to act accordingly.
What if things change and times are not going as well? The overall number of patrons drastically decreases, not enough electricity (ATP) to run the restaurant or running water (redox potential)? What if disaster is about to strike? How can the restaurant prepare all the managers, employees, the building, the doors, the patrons for it?
Luckily the restaurant has a monitoring system that can quickly make sure the restaurant will be ready for anything that comes its way. The monitoring system can take snapshots of all data generated by the restaurant: power supply, water supply, patron count, employee count, conditions outside the restaurant like weather or competing restaurants. The monitoring system is the bacterial second messenger systems. With the support of the managers, the monitoring system can instantaneously keep track of all variables and make changes as needed.
The system is detecting the start of a drought. This drought will lower the number of patrons coming and going from the restaurant. The drought will also change the available electricity and water supply of the restaurant. The monitoring system sounds the alarm, a message is sent over the intercom for all the managers and employees to hear and react to. The intercom message alerts some managers to call in additional employees while telling others to stop their work. Some employees take on a new job in preparation for the drought. The intercom message is the bacterial second messenger cyclic-di-GMP. The entire restaurant begins preparations for the drought so it can survive until better times are present. Other than changes to managers and employees, some new employees are called in to prepare the building itself. Perhaps to change the number of doors. The employees may also change the exterior of the building to better withstand the drought like changing a wood exterior to a brick or stucco one. The brick or stucco are the exopolysaccharides, complex sugars on the exterior of the cell that can serve as protection or to help cells adhere to each other to ride out the hard times together.
When times change, the restaurant has to be able to change with them. That is why these restaurants have been in business for ~3 billion years and still going strong.
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!
A 1500 ring circus from a typical bacterium.
Continuing on the theme that bacteria are Nature’s smallest circus, I want to highlight the most glaring problem with our knowledge of these 2000 ring circuses. We have discussed how proteins encoded by genes within a microbe’s genome often work together to carry out their function, i.e. pathways (or rings). To date, according to the NCBI genome site 4019 bacterial genomes have been sequenced to the point that we know the number of genes and proteins each organism contains. Moreover, this equates to 7,309,205 genes total or roughly 1818 genes per genome. These are astonishing numbers. To show our futility as experts of all things natural, over 30% of these genes are considered hypothetical or uncharacterized. In some genomes, these genes make up 60% of the total genes. These terms are a technical way of saying “hell if we know what they do”. Computers have recognized them as genes or open reading frames, however, the gene itself isn’t similar enough to known or characterized genes for scientists or computers to call it “the same”. If these gene products (proteins) functions are unknown, they cannot be assigned to a ring in the circus therefore making the largest ring by far in any bacterial circus the “unknown” ring.
Recap: The restaurant is the bacterial cell, the employees are the proteins/enzymes that serve the patrons which are the compounds/metabolites.
Who are the bosses that determine which, and how many, employees are needed for each type of patron?
The restaurant managers have a very important job to perform. They have to make sure the right number of employees are available to help their respective patron. If the balance between employees and patrons is not well maintained, it could cause disaster for the restaurant itself. In a past post, I tried to describe how bacteria made decisions. One of the predominant ways was the use of two-component systems. For this story, think of the restaurant managers as actually two people who need to work well together. One identifies its respective patrons and the other makes changes to the number of employees for those patrons. It is this balancing act that helps the entire restaurant to work smoothly.
A successful restaurant will open up new locations. The same can be said for bacteria. If conditions are right, the cell will divide into two cells. As with a cell, restaurants have to make sure certain activities are undertaken to ensure the new restaurant will be exactly like the successful one it is copying. The success of this restaurant is based upon the ability to keep the employees happy (by having patrons to serve and not sitting around bored) and keeping the patrons coming in. To duplicate this success, the new restaurant should have a building exactly like the current one so the patrons will easily continue to enter and leave. The new restaurant will also need the exact employee list for the managers to call upon when needed. The employee list is the genome of the cell that encodes the proteins needed for survival. That would make the copy machine that duplicates the employee list the DNA replication machinery. This special restaurant building is state of the art. It can expand until it is roughly double its original size then place a dividing wall down the middle of the large building until the building becomes actually two buildings. Now the restaurant can serve twice the number of patrons with the same efficiency as before. Each new building has the same employee list and rough the same number of employees to start off with. Then the managers start their work identifying the patrons in the restaurant to make sure the employees are there to serve them.
The two buildings shake hands and go their merry way…ready to serve.
In Part III, I will talk about the intercom system that allows major changes to happen to the kind of employees needed for economic downturns.
Many say storytelling in science is a great way to describe complex material in an understandable way for the masses. In this post, I will try to use an analogy to illustrate the complexity of a typical motile bacterial cell.
Microbial Physiology through Storytelling
If there is anything Americans know, it’s food. We are a nation obsessed with food and frequent restaurants on a regular basis.
Imagine your favorite restaurant as one huge bacterial cell.
When I travel to another city, I can’t rely on habit to guide me to a restaurant for dinner. I have to search for it while driving down the road. In order to know when I have found the restaurant I am searching for, I must rely on signs telling everyone what the restaurant is. The sign is a way to recognize and identify the building as i) a restaurant and ii) the specific type of restaurant. Bacteria do the same. They have ‘signs’ (proteins and other molecules) attached to the outside of the cell that lets other cells around identify what the cell is. I go into the restaurant through a door that allows patrons to move in and out of the building like bacteria have gates or channels that allow molecules to move in and out of the cell. Almost always, patrons are different leaving than they were when entering the restaurant; filled with yummy food they consumed and perhaps stopping to make a deposit in the waste room before leaving. Many molecules that leave a cell are different than those that enter. The workers of the restaurant have to keep track of the number of patrons entering and leaving the building to efficiently serve the patrons. Each employee has a specific job to do for very specific patrons. The employees have to identify their patrons and serve them as described by the bosses. Bacteria have an array of workers (proteins and protein complexes) that have very specific job descriptions depending on the patrons (substrates and product molecules) present in the cell. The restaurant survives by serving as many patrons as possible efficiently and correctly just as a cell must survive by responding correctly and quickly to everything in its environment.