Storytelling in science: Metabolic pathways as circus rings

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!

bacteria, metabolism, pathways, microbiology

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.

Storytelling in Science: The Cell as Your Favorite Restaurant Part II

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.

Storytelling in Science: The Cell as Your Favorite Restaurant Part I

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.

First Order of Business When Rich: One Microscope Per Child

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

It is really sad humans (that seem so determined to destroy this planet) show little regard to the majority of species, most of which are invisible to the naked eye. Most people go through life without knowing the splendor of Mother Nature in all its glory.

It’s hard to believe now the accepted knowledge of society before invention of the microscope around 1590 by Zacharias Janssen (disputed). Everyone had  to rely on their own eyes, while exquisite in their own right, but these are only reliable down to the size of a human hair width. Imagine a world where flies and maggots were thought to spontaneously generate from items such as rotting meat. This was the common knowledge and understanding. After human observation was enhanced by wonderful inventions such as the compound microscope, only then could the true understanding of all things small or distant be studied in acceptable depth.

Imagine if you will looking through a microscope for the first time. You have been told, and believe, you live in a clean world in which if you can’t see it, it does not exist. With true curiosity and virgin eyes, you place a drop of water on a small glass slide and focus upon it with a microscope. Small particles that appear to be moving as if they were swimming come into view. Suddenly, your whole world changes. At the intersection of ignorance and knowledge, powerful things happen.

Today, microscopes have evolved and improved to the point where we can visualize hydrogen bonds in molecules at the atomic scale. The invention of the electron microscope helped usher in the field of virology just as Antonie van Leeuwenhoek did so much for microbiology with his improvements to the light microscope. The gifted van Leeuwenhoek discovered red blood cells, cell vacuoles, and bacteria (among other things). Thanks to him, the use of a microscope became a useful technique in various types of research.

It is said that ignorance is bliss. However, I believe ignorance is…ignorance. The less a person knows and understands, the smaller their world and the less their ability to imagine and perceive new ideas. Seeing is believing and what better way to see beyond your means than with a microscope.

Now, imagine giving this enormous ability to see the unexplainable to the most curious and imaginative of us, children. Their innate curiosity and unobstructed ability to use their imagination makes the power of the microscope exponentially greater. Giving a child this portal to the unseen opens their eyes to endless possibilities, probing questions, and the ability to answer the questions themselves.

I support the One Laptop Per Child movement. Opening up the entire world of information to a child can open up new possibilities and lead to a better life. The laptop opens the world to the child, but a microscope opens the child’s world in which they live. The knowledge gained is not flat and two dimensional; it is in real 3D.

Yeah, when I’m rich, One Microscope Per Child is my first action.

Never underestimate clever bacteria: bacterial persistance

If there is anything I try to convey to anyone who will listen: never underestimate the intelligence of bacteria. A new case-in-point was published in the journal Infection and Immunity (Abstract only- Paywall) from researchers in Buffalo, New York to back up my claim. Former knowledge from two pathogens that cause strep throat, ear infections, and colds suggested they did not survive long outside the human body. However, a new study about Streptococcus pyogenes and Streptococcus pneumoniae suggests we were wrong and the bacteria were right.

Previous studies used unnatural conditions; i) cells grown in broth media and ii) free-living cells. These both are not encountered by bacteria which invade a human host. S. pyogenes and S. pneumoniae both infect humans as biofilms; very resistant, closely-connected bacterial communities. The present study used biofilm bacteria to test how long these bacteria could survive outside the body and still infect mice.

To drive the message home, researchers tested a day-care center for S. pyogenes and S. pneumoniae living on surfaces and capable of causing infection. Results indicate these bacteria were found at high levels and viable even after surfaces were cleaned before sampling.

Let me re-iterate: bacteria know survival. Don’t underestimate their ability to evade our most clever defenses and come out on top while we lay in bed recovering.

News Flash: Cook Your Chicken (like you have been)

I personally have a Google News section for “Bacteria”. I was shocked by the headlines I have read today:

After being told for years not to eat raw chicken, yet again, we are reminded why.
After being told for years not to eat raw chicken, yet again, we are reminded why.

How is this news? We have a general understanding around our house, “Raw chicken is the dirtiest thing you can bring into the house”. Even my four year old knows this. Through many years of research, countless studies have shown the quick adaptability of bacterial species to the over use of antibiotics. This has rendered most common drug treatments for bacterial infection useless.

However, bacteria have NOT adapted ability to resist some common treatments like alcohol, bleach, UV radiation, and heat. I do not recommend cleaning tomorrow night’s chicken with alcohol or bleach. I personally would go with heat. So, please, next time you want to make a chicken dinner, be safe and cook it as recommended.