Talmudic Question #30

Many bacteria, e.g., E. coli and B. subtilis, regulate their gene expression via a large number of distinct devices that operate on almost all conceivable biochemical levels. Why so many?

Comments

[Stephen M. Boyle]

Homeostasis, of course. Such a relatively simple life form needs as much flexibility it can muster in its complex environment ie from the macrophage to the soil.

[Celia M. Ebrahimi]

Bacteria possess a multitude of regulatory proteins (ex. kinase, phosphatases just to name a couple) that are responsible for ensuring their ability to control their structure, function, differentiation and adaptation to environmental conditions. In addition many of these regulatory proteins have overlapping functions with other regulatory proteins. This leads one to ask the obvious question – why would a bacterium want so many regulatory proteins and why have regulatory proteins with overlapping functions?
The second half of this question is easy to answer. Having two regulatory proteins with overlapping functions ensures that the proper regulation continues to occur even in the absence of one of the regulatory proteins. For example the synthesis of (p)ppGpp is regulated by two proteins: RelA and SpoT. In the absence of RelA the synthesis of (p)ppGpp still occurs and is still detected in the cell thanks to SpoT. The overlapping function of SpoT ensures that (p)ppGpp expression remains “normal” under nutrient rich and nutrient poor conditions, thus allowing the cell to respond accordingly. Therefore, overlapping regulatory proteins function to ensure the proper regulation of numerous cellular processes essential for bacterial survival.
The first half of the question asks, why would a bacterium want so many proteins? Numerous bacterial proteins have been implicated to perform essential functions in fairly simple tasks such as cell growth and division. One possibility for the abundance of so many bacterial proteins is to ensure that the executed task is being performed correctly. For example, each protein in the RNA transcription complex performs functions in ensuring proper gene expression (ex. alternative sigma factors recognizing elements in the promoters of stress response genes). The loss of one of these factors could have a significant negative impact on cell survival. Another reason why there are so many bacterial proteins is to ensure that bacterial tasks are executed only when required. For example, induction of the stress response pathways occurs via a signaling cascade event involving numerous proteins and resulting in a change in gene expression. Each of these proteins in the signaling cascade event could function as a checkpoint to ensure that unnecessary changes in gene expression do not occur. A final reason why bacteria have so many proteins may reflect the ability of the bacterium to “fine tune” cellular processes to allow for optimal survival. Having the ability to change a single protein in a protein complex may optimize a bacterial metabolic process thereby enhancing bacterial fitness.
Therefore, the abundance of proteins in bacteria allow the bacteria to control when and how cellular tasks are executed and to ensure that each task is performed optimally.

Celia M. Ebrahimi (Student, Integrative Microbiology course)

[Ilham naili]

When you are a single cell, and the only thing “on your plate” is to be best fitted for survival, control of gene expression is no game!
Some bacteria out there managed to adapt to some of the most amazing environmental conditions, by developing complex pathways for gene regulation, many of which involving profound changes within the cells and thus occurring at a high cost. Additionally, it is noteworthy to mention that some regulation mechanisms, such as sporulation to keep Moselio’s example, can lead to a dramatic decrease of fitness if the cell does not properly time this process. Therefore, bacteria have their interests in developing several ways to sense their environment before making a major switch in its gene regulation. It then seems strategic for the microbes to implement several checkpoints in distinct biochemical pathways, which ensure a more precise control of gene expression. One “stress” signal might be a false alarm; two different stress signals coding for the same message might not be that random anymore.
In my opinion, the establishment of regulation networks within bacterial cells is a smart, cost effective mean to get continuous feedback from the intracellular and extracellular environments, and rapidly adapt to changing conditions that could affect growth and survival of the cells. Microbial cells can’t afford to make the wrong decision, because of its probable lethal outcome.
If I was a bacterium, I would certainly like, before launching a major regulation switch, to verify the trustworthiness of my source of information and back it up with some other signaling pathways. Just in case…

Ilham Naili (Student, Integrative Microbiology course)

[paula patterson]

The reason that comes to the minds of many for why regulate cellular processes would be to save energy. Any action a cell decides to take will expend energy and resources. Whether the cell is replicating or transcribing DNA, translating a protein, or simply degrading cellular components that are no longer needed, energy is being used. The real question is whether or not the energy expended is substantial compared to the total energy supply of the cell. I believe that the energy used up is a small enough fraction of what the cell has at its expense, that regulation is really not about saving energy. Rather I think regulation is necessary in order to adapt and thrive in a variety of environments in order to promote survival. A cell is provided with a number of signals at any given time. It is the prioritization in response to these signals that determines what environment and what conditions the cell will adapt itself to. A prime example of such prioritization is the Lac Operon. A cell benefits the most from the uptake of glucose and without regulation, if glucose and lactose were both around there may be no distinction made between the two sugar energy sources. In order to benefit the most from its environment, a cell should uptake and use the glucose rather than the lactose. Aside from the prioritization of which food source to choose to provide the most benefit, there are more serious consequences of a lack of regulation. In times of starvation, a cell can choose to turn on motility or sporulate. Sporulation is a committed pathway that a cell cannot reverse. If a cell were to enter this pathway at the wrong time it would result in the death of the cell rather than its survival via a spore.
In order to prioritize such cellular events, there must be regulation at every possible level. There must be regulation at the level of transcription so gene transcripts that are not needed for the current environment are not floating around within the cytoplasm. I believe this level could be more lax as making a transcript does not guarantee its translation. Regulation at the level of translation should be stricter as unnecessary proteins acting within the cytoplasm will alter prioritization or slow a switch to a new nutrient or environmental stimulus.
In short, a cell needs a variety of regulatory mechanisms at every level in order to prioritize its activities in order to adapt to its surroundings and prolong its life.

Paula Patterson (Student, Integrative Microbiology course)

[Amin Talebi Bezmin Abadi]

I agree with Judith Schaechter s' remarks .
Bacteria like B.subtilus can survive in many wide-range of environment . It need to have complete and comprehensive features that control by complex gene experssion .
Amin Talebi Bezmin Abadi

Tarbiat Modarres University

[Paul Orwin]

Because I like to be a contrarian; in what sense do they have a lot of regulatory mechanisms? This is similar to what Tim said, but I'm sure no one on this site would underestimate the complexity of microbial lifestyles! If the question is interpreted more narrowly as why have regulation at all levels, instead of just transcriptional or translational, or allosterically, I'd imagine it is more or less the difference between needing to act fast (protein level regulation of motility, for example) vs. acting carefully/judiciously, i.e. the difficult and irreversible(ish) decision to become a spore. Different modes for different choices, and all that. We all know that small isn't simple....

[Shaun Brinsmade]

I agree with Tim - in some cases, the bacteria will execute genetic programs that will take them beyond the point of no return that will give them a disadvantage if prematurely activated (e.g., sporulation, although it can apply I am sure to other processes). Furthermore, multiple layers of regulation allow for a biological "rheostat" to yield precisely the amount of gene expression necessary and suficient to complete the task at hand.

[Tim Denny]

I believe that ALL bacteria employ complex regulatory processes to control their gene expression (we only know about these processes in the few extensively studies bugs). I tell my students this is because bacteria cannot afford to make any mistakes in gene expression that would result in unprofitable expenditure of energy or nonadaptive changes to their environment.

[Judith Schaechter]

to cover all bases? To make sure the job actually gets done?...I'm just guessing.