Showing posts with label bacteria. Show all posts
Showing posts with label bacteria. Show all posts

Thursday, November 2, 2017

Extremophiles Are Key, Or Archaea

Biology concepts – archaea, bacteria, domains of life, hydrothermal vent ecosystem, chemosynthesis

What is a bigger mistake – to overestimate or to underestimate? If you overestimate someone, you may be disappointed with the result. If you underestimate, you may never realize what they are capable of accomplishing. What is more, your underestimation may cause you to miss incredible things already taking place.


Underestimate the power and importance of
wee small things at your peril. The atom holds
extreme amounts of energy, and we depend on
the tiniest of prokaryotes for our survival on Earth.
It would be a mistake to underestimate the grit and power of some of nature’s smallest organisms. We could talk about this for months, but why don’t we stick to the discussion of prokaryotes and their ability to get along without conventional organelles that we began last week.

We can go farther in praise of the prokaryote by looking at how some of them manage to live in the most inhospitable environments; places that would kill us in seconds, or at least we hope they would. These are the “extremophiles;” the name makes them sound like Saturday morning cartoon superheroes.  For example, Thermococcus gammatolerans is the most radiation tolerant organism on Earth. It can laugh at gamma radiation levels 100x higher than other resistant organisms, even though it lives at the bottom of the sea.

As a result of the molecular biology revolution, many of the extremophiles are now called Archaea (Greek for “ancient”) or archaeabacteria, a completely group of organisms. Archaea are older than bacteria, and but they have some similarities to bacteria. Archaea are generally smaller than bacteria, but the cell wall of most archaea looks just like that of Gram+ bacteria. This is a thicker cell wall than that of Gram- bacteria, and takes up the Gram stain, hence the name Gram+.


The archaea cell wall is thick, and is contiguous with the cell membrane, 
like that of Gram+ bacteria. Gram- bacteria have thinner walls and 
they have a periplasmic space between the wall and the membrane.
Just looking at archaea and bacteria through a microscope makes it hard to tell the difference between these two distant relatives. It is at the molecular level that most of their differences become apparent. The way that archaea make RNAs is more eukaryotic than bacterial and while they both have cell walls, the lipids that make up archaeal membranes are quite different. Archaea lipids are hydrocarbon based, not fatty acid based like those of eukaryotes and bacteria. Also, archaeal cell walls lack the peptidoglycan that is characteristic of bacterial cell walls. Peptidoglycan synthesis is a common target of antibiotics, like penicillins, cephalosporines, and vancomycin.

This last difference might work out O.K. for us as humans. Not a single disease can be attributed to an archaea – yet. This is a big exception. Every other group of organisms on Earth has at least some members that can do humans harm, even if only inadvertently. Fungi, protozoa, bacteria, even plants can all cause us harm. One study says it is unlikely that we have just missed disease-causing archaea. About 0.38% of bacterial species cause disease, so if diversity in archaea is similar to that in bacteria, we should have found about 20 disease causing archaea by now.

Gum disease (periodontitis) has an outside chance of having an archaeal cause, but the evidence is sketchy. In a couple of studies, the presence of archaea in the mouth has correlated with gum disease; if archaea were present, then there was disease. Also, higher archaea number correlated to more severe disease. But archaea were only present in 1/3 of all cases of periodontitis – this is not good evidence to say archaea are the cause of periodontitis. This is the closest we have come to finding an archaeon with an anti-human bent.

Some archaea are thermophiles (heat loving); they don’t just like it hot, some require it really hot. Many thermophiles live in near undersea hydrothermal vents, where heat from the Earth’s mantle and core escapes into the ocean; basically ocean volcanoes.


The hydrothermal vent is an ecosystem that one
would be hard pressed to call home. Varies from 700˚C
to 4˚C, it is acidic, toxic, and radioactive. Yet many unique
prokaryotic and eukaryotic organisms live nowhere else.
To each his own.
Near a thermal vent, the temperature can reach 400-410˚C (700-720˚F) . The water doesn’t boil because of the great pressure exerted on it by all the water above it. No eukaryotic organism can survive at these temperatures, but thermophiles like T. gammatolerans do just fine. The hydrothermal vents pour out high levels of gamma type ionizing radiation from deep in the Earth, so it is handy that this archaeon is a multi-extremophile.

Only a few feet away from the vent the temperature of the ocean bottom will remain near freezing, about 4.5˚C. Other archaea (and some true bacteria) thrive in this cold environment. Called psychrophiles, cold tolerant archaea have cell walls that resist stiffening in water that is even below freezing temperature, and can fill there cytoplasm with anti-freeze proteins (AFPs; they create a difference between a solution melting point and its freezing point, called thermal hysteresis).

Between these two extreme environments, you can find quasi-conventional animals. As the hydrothermal vent water gives up its heat to the surrounding ocean, it creates an area that holds a temperature of about 10-15˚C. Many interesting animals have been found in this area, including the yeti crab and tube worms. Data from January 2012 describes a pure white octopus found at a depth of 2,394 meters. At this depth there is no light, so the octopus has no need for the elaborate camouflage mechanisms of color and texture. This octopod may represent a new species, but other white, vent-dwelling octopuses have been described previously, just not this far south.


This is the yeti crab (Kiwa hirsute). It is white because it lives
in the dark. It is furry because……..well, it makes the name
appropriate. Actually, the setae (hairs) contain bacteria that
may act to detoxify the water from the hydrothermal vents
where it lives. And it isn’t really a crab either, but I’m not
going to tell it so.
Ultimately, even these animals depend on the archaea for survival. No photosynthetic producers can survive at these depths, so the food chain starts with the chemosynthesizing prokaryotes, particularly those that use hydrogen sulfide to produce energy. Hydrogen sulfide is a major constituent in the hydrothermal vent output…. and would kill us quickly by binding to the enzymes in our mitochondria that perform ATP synthesis.

Some animals, like snails, eat the chemosynthesizing prokaryotes directly, while others predate the snails, etc. On the other hand, tube worms (Riftia pachyptila) get their energy directly from thermophilic proteobacterium that live inside the worm in a symbiotic relationship.

Other archaea live in high salt environments, like in the Dead Sea or the Great Salt Lake. They must be lonely, because given the high salinity, they are the only things living there (Water, Water Everywhere, But….). On the grosser end of the scale, some archaea thrive in human sewage plants, working well in environments without oxygen and high nitrogen contents.

Archaea have also been found in natural asphalt lakes, like near the La Brea region of Trinidad and Tobago. With toxic gases, high temperature, and practically no water at all, it was surprising that scientists found so many different kinds of prokaryotes, including several types of archaea. These 2010 findings suggest that life on other planets might not necessarily depend on water – that would be one heck of an exception!

But not all archaea are extremophiles, and they turn out to be much more common than we had thought. This isn’t just a numbers game, it turns out that we have been underestimating their effects on our lives all along. For instance, nitrogen fixation is crucial for crop production. A 2006 study by Schleper et al. in Norway suggests that there are many more ammonia oxidizing archaea in the soil than there are nitrogen fixing bacteria.


Archaea are responsible for much of the primary production that 
occurs in the soil and in the water. Just the methanogenic 
archaea alone are responsible for nearly 2% of all the carbohydrates
produced on Earth. Archaea contribute to the primary production 
of every ecosytem.
Further, current evidence suggests that archaea may represent 25-84% of all primary production (creation of carbohydrates and other organic compounds from inorganic carbon sources, whether by photosynthesis or chemosynthesis) in the upper layers of seawater. Primary production is the beginning of every food chain, so ultimately all of our food depends on archaea as well. To bad that we have been underestimating our dependence on these oldest of life forms. Who knows what our effects our life choices have been having on them all these years.

On the other hand, not all extremophiles are archaea either. Thermus aquaticus is a bacterium that lives in hot sulfur springs and geysers. It is a chemosynthesizing bacterium that has become important in molecular biology. Since its enzymes can tolerate high temperatures, it is useful for replicating DNA sequences in the lab using the polymerase chain reaction. One step in this reaction requires high temperature and would kill most other enzymes. 

Amazingly, this PCR technology and T. aquaticus polymerase has been crucial for helping us see how important the archaea have been in our evolution. In 1977, scientists Carl Woese and George Fox began DNA sequencing of some the extremophiles. They recognized that archaea were very different from eubacteria. The two groups must have diverged long long ago.


The three domains of life are shown here. The length of line shows 
the evolutionary distance between domains. You can see that 
Archaea are more like us than are the bacteria. You can’t tell from 
this chart, but Archaea are older too. They are the roots
of our family tree.
It turns out that Archaea are as closely related to eukaryotes as they are to eubacteria. This stood science on its ear. Up to this point, scientists had been arguing as to whether there were four, or five, or six kingdoms. Now they had to impose a higher classification which superseded all the kingdoms.

Woese’s evidence has led us define to the three domains of life. One domain is the eukaroytes, all the cells with a nucleus (with exceptions, but we can talk about those later), with linear chromosomes instead of one circular piece of DNA (again with exceptions), and with organelles. The second domain is the archaea and the third domain is the bacteria. Six kingdoms follow from these domains; archaea, bacteria, protista, fungi, plantae, and animalia.

Archaea, bacteria, and eukaryotes; we have shown that they are all different, and yet they all developed from some single precursor cell. Next time we will see if our discussion to this point gives us a roadmap to get from that ancient first cell to us.


Rogers, A., Tyler, P., Connelly, D., Copley, J., James, R., Larter, R., Linse, K., Mills, R., Garabato, A., Pancost, R., Pearce, D., Polunin, N., German, C., Shank, T., Boersch-Supan, P., Alker, B., Aquilina, A., Bennett, S., Clarke, A., Dinley, R., Graham, A., Green, D., Hawkes, J., Hepburn, L., Hilario, A., Huvenne, V., Marsh, L., Ramirez-Llodra, E., Reid, W., Roterman, C., Sweeting, C., Thatje, S., & Zwirglmaier, K. (2012). The Discovery of New Deep-Sea Hydrothermal Vent Communities in the Southern Ocean and Implications for Biogeography PLoS Biology, 10 (1) DOI: 10.1371/journal.pbio.1001234

For more information and classroom activities on archaea, hydrothermal vents, chemosynthesis, and domain/kingdoms, see:

Archaea and extremophile bacteria –

Hydrothermal vents –

Chemosynthesis –

Domains/kingdoms -

Thursday, October 26, 2017

Simple Ain’t So Simple Anymore

Biology Concepts – prokaryotes, simplicity, complexity, organelles, microcompartments


Not everything new is better; new doesn’t
necessarily mean improved. Remember the
“New” Coke debacle?
Newer is better, right? Everything old is simple and plain. Back in the good old days, you had to read a book, but today you can browse the internet and pick from 8000 songs while you drive to the superstore to pick up a Kindle. Today is faster. Better. More complex?

How about living in 1800. Could you catch and kill your dinner with a trap of your own making, followed by gutting and dressing it on the back porch of a house you built with your own hands, while you try to keep your entire family from being eaten or dying from an infected scratch?  Now whose world seems complex!

This same belief has been applied to forms of life. Bacteria are old and simple; we are new and complex. Plants and animals can do millions of things that bacteria can’t, because they are so simple and primitive and we are so high tech, biologically speaking.

But it is a mistake to call bacteria simple or primitive. They may not have all the bells and whistles that eukaryotic (eu - true and karyo = nucleus) cells have, but they have survived much longer than other life forms, and they outnumber us by billions. There are more bacteria in a handful of rich soil than people who have ever lived on Earth. So don’t confuse complexity with success.

A cursory look at bacteria would suggest that they are indeed simple. They are bags of chemicals, without the complex organelles that mark eukaryotic cells. Plus, they're small; the whole organism is just one cell. They have just one chromosome and fewer genes than eukaryotic cells. It would be easy to see them as simple.

Even at the biochemical level prokaryotes (pro = primitive) appear simple compared to eukaryotic cells. Our more modern cells aren’t satisfied with just making more proteins, they also modify many of these proteins, adding carbohydrates, acetyl groups, phosphate groups, sulfur groups, etc. These post-translational modifications (after peptides are translated from mRNA messages) are crucial for different functions and for interactions with messengers and DNA.


Histones are protein complexes that help DNA to coil up into tight 
configurations. But DNA it is tightly packaged, it is hard for 
individual genes to be transcribed and made into protein. Histone 
acetyltransferases are enzymes that add acetyl groups to the histones 
and open DNA to be read. Histone deacteylases do the 
opposite, they add acetyl groups and cause the DNA 
to tightly coil.
The exception here is that less than a decade ago scientists found that many prokaryotes also do some kinds of post-translational modifications, includingphosphorylation and acetylation. Acetylation, the addition of a -COCH3 group to a molecule, is important in eukaryotic cells for several reasons, not the least of which is in determining which DNA is open to be replicated or transcribed (copied to mRNA).

Data from 2004 was the first to show that prokaryotes can carry out phosphorylation (addition of PO3 groups) to proteins. What is more, acetylation and phosphorylation are reversible modifications, so an additional layer of complexity is added. Prokaryotic proteins have one function when modified and another when not modified, just like modification of eukaryotic proteins. Sounds like prokaryotes have more going on than we thought.

Prokaryotes are the real success stories of life on Earth. They can do things some things eukaryotes can’t do (more on this next time). Even more amazing, every deficit we have said they have - they can’t do this, they don’t have those – can be seen as a reason they are more amazing.

Prokaryotes are single celled organisms, so they have less specialization. But this means that the cell has to carry out every function that the organism needs. Could your fat cells produce antibodies and kill off protozoan invaders? I think not. We also poke fun at prokaryotes because they don’t have organelles; but this means they have to find a way to do all their chemistry in one big open environment, much more difficult .……….or maybe not.

That classic rule of biology, "eukaryotic cells have organelles and prokaryotic cells don’t," may not be completely true. This would be a big exception.  Evidence shows that many kinds of prokaryotes do have local environments, called microcompartments. We have all been living a lie!

The most studied of the microcompartments is the carboxysome. This hollow shell, first described as far back as 1956, holds enzymes (RuBisCo, see When Amazing Isn’t Enough) that many prokaryotes use for carbon fixation. Photosynthesis is the most obvious type of carbon fixation, where carbon in a gas form (CO2) is converted to carbon in an organic, solid form (carbohydrates).


Carboxysomes as seen by electron microscopy. They really
do look geometric. The faces and corners are specific groups
of proteins, and hold the enzymes inside the microcompartment.
There are minute pores where the proteins come together
to let reagents and products move in and out of the carboxysome.
RuBisCo is a fairly inefficient enzyme, so sequestering it with its substrate inside a microcompartment works to increase the production of energy. Doesn’t this sound a lot like one of the key reasons for the development of organelles – the bringing together of reagents for increased efficiency of reactions?

But it is not just photosynthetic bacteria (cyanobacteria) that use carboxysomes. Many other autotrophic bacteria (auto = own and troph = food) use carboxysomes to fix carbon during chemosynthesis. Chemoautotrophs, for instance, are organisms that use chemical energy rather than sunlight energy to fix carbon.

In many prokaryotes, the oxidation of hydrogen sulfide or ammonia (a nitrogen containing compound) provides the energy for producing organic carbon; Thiomargarita namibinesis from our posts on giant bacteria uses sulfur for chemosynthesis. But there are also organisms that use the energy from the production of methane to drive carbon fixation. You have undoubtedly had experience with intestinal prokaryotes that produce methane gas (methanogens) – don’t try to say you haven’t.

The carboxysome (as a model of many microcompartments) is not a membrane bound bag as organelles are in eukaryotes. Carboxysomes are more like soccer balls made of protein, but in this case they hold a rigid polyhedral form and don’t get bicycle kicked into a prokaryotic net by Pele.

Each face of the shell is made up of a two dimensional polymer of protein hexagons. However, as architects will tell you, this is a difficult shape to close using only hexagons, even with 10,000 of them, like the typical carboxysome has. Soccer balls and the dome at the Epcot Center use strategically placed pentagonal faces that allow for the turning of the hexagonal faces and a closing of the compartment (see cartoon above).


These are cartoons showing the structure of a
carbon fullerene (right) and a carbon nanotube
(left). Each green sphere represents a carbon atom.
These structures are very strong, like for making
bicycle helmets. They may also become useful for
things like space elevators, nanoelectrical circuits,
and solid lubricants.
We have used this hexagonal and pentagonal combination for decades, but it was identified in bacteria less than five years ago. This arrangement is also seen in viral protein coats, as well as in carbon fullerenes, which are superstable carbon nanostructures described in 1985 and named for the inventor of the geodesic dome, Buckminster Fuller.

Could this be the exception – nature stealing an idea from humans? Probably not, I’m guessing Dr. Fuller independently happened upon the same solution that nature had worked out millions of years ago – but it took a heck of an intellect to recognize a good thing.

It might be lucky for us that Fuller’s domes had us looking for this combination in other areas. Carboxysomes are present in up to 25% prokaryotic pathogens (disease causing organisms), and current research is aiming to disrupt the formation of the hexagonal/pentagonal compartments as a way to kill, or at least slow down, the microbes. So many prokaryotic pathogens are developing resistance to traditional antibiotics that a new approach will be heartily welcomed.

There are other microcompartments besides the carboxysome. The bacterium Clostridium kluyveri is proposed to have a metabolosome compartment for the conversion of ethanol into carbohydrates. Furthermore, Salmonella enterica, is capable of producing two different metabolosomes; one for propane-1,2-diol and one for ethanolamine, for conversion of these substrates into energy-containing carbon sources.

The evidence of these additional microcompartments makes one wonder just how many different species of protein shelled microcompartments there may be. To investigate this question, a group from UCLA recently published a study using comparative genomics (comparing genes of similar and dissimilar organisms to find groups of genes of similar function) to point out possible enzyme pathways that may be sequestered in microcompartments.

Their late 2012 study suggests that new types of microcompartments for different types of propanediol metabolism, and the identification of microcompartments in organisms for which they were previously unknown, like mycobacteria. The genomic evidence also suggests new types of protein shells, differing compartments being used for differing variants of enzyme function.

It is in these final examples that we see a more concrete purpose for the microcompartment. During the metabolism of alcohol, propane-1,2-diol, or ethanolamine, a compound called acetaldehyde is formed. This is a toxic product that needs to be converted to acetic acid in rapid order to avoid toxicity to the cell. By isolating the acetaldehyde in the metabolosome, S. enterica improves its own living conditions. This is also important to us humans.


This is not a before and after picture for an embarrassing
karaoke incident. This is a demonstration of the facial
flushing reaction when a person has an ALDH2 mutation, and 
can’t metabolize alcohol efficiently.
Many Asians and Ashkenazi Jews have a mutation of the acetaldehyde dehydrogenase (ALDH2) gene that produces the enzyme that rids the body of acetaldehyde after the consumption of alcohol. The mutation produces a poorly functioning enzyme, so acetaldehyde builds up in their systems and causes a facial flushing reaction. If both ALDH2 genes (one from mom, one from dad) are mutated, the person gets violently ill from consuming ethanol. As you might imagine, populations in which this mutation is prevalent have very low rates of alcoholism.

So we have the exception that prokaryotes are not really without organelles; theirs just look different. Could you guess that the exception goes the other way too? Well, it does. The nucleus of eukaryotic cells works with microcompartments that allow certain things in and out, but keep your DNA inside the nucleus.

The pores of the nucleus (Cells Are Great Multitaskers) are complex openings made up of many proteins. Why? Nuclei could just use receptors to allows certain things in or out, similar to the system used by the cell plasma membrane. But evolution went with a more complex solution.


The vault complex is made of 78 identical protein chains.
One chain is shown in white. Together, they form a
microcompartment that is crucial for our nucleus function.
There is a protein microcompartment called a vault complex that works with the pore complex. This is a highly regulated way of moving RNAs and ribosomes (made in the nucleolus which is inside the nucleus) out of the nucleus, while keeping your DNA inside. I don’t think it is a hard concept to grasp that you cells are happier when your DNA stays inside the nucleus; do you keep your valuables on your front lawn?

Next time we will see how the nucleus, its pore complex, and its microcompartment carriers helped us make the jump from prokaryote to eukaryote. The nucleus is a later evolutionary development, but it still uses a prokaryotic system. This is clue that helps us investigate our cellular family tree. 





Jorda, J., Lopez, D., Wheatley, N., & Yeates, T. (2012). Using comparative genomics to uncover new kinds of protein-based metabolic organelles in bacteria Protein Science DOI: 10.1002/pro.2196




For more information or classroom activities on bacterial microcomponents, post-translational modification of proteins, alcohol metabolism, or the vault complex, see:

Bacterial microcomponents –

Protein post-translational modification –

Alcohol metabolism –

Nuclear vault complex –
http://en.wikipedia.org/wiki/Vault_%28organelle%29

Wednesday, June 22, 2016

Antibiotics Are Going Viral

Biology concepts – bacterial immunity, bacteriophage, antibiotics

There are recognized characteristics that all living organisms 
share. However, they are not black and white; take a look at 
these characteristics and think about fire. Fire grows, 
consumes energy, gives off energy, metabolizes, reproduces. 
So if fire can be fit into some of these, maybe an argument
can be made for viruses?

Many scientists do not consider viruses a form of life, but that doesn’t mean the idea is universal. Even virologists can’t agree. Viruses do blur the lines between life and non-life, and it gives us something to debate when parties get quiet. It makes for a great debate in Biology classes too, if you don't have a party to go to.

For many, it comes down to this - viruses don’t react to changes in their environment, grow, or metabolize, so they can’t be alive. They lack all these characteristics because these processes take energy, and viruses themselves don’t make or consume energy. This is a big sticking point for anyone trying to make an argument for including viruses as life.

But they seem to do O.K. at making their way in the world, and are becoming quite the model for immune stimulation. A 2011 study at the Emory Vaccine Center used virus-sized nanoparticles to try to induce life-long immunity as natural viruses do. It is hypothesized that virus particles bind to several different types of innate immune receptors (called Toll-like receptors, TLRs) and this diverse stimulation by one antigen is responsible for longer immunity.

The nanoparticles were composed of a synthetic polymer particle complexed with two stimulators. One is similar to a part of the bacterial cell wall, and the other mimics viral mRNA. The particles also stimulated several different TLRs in mice, and it is hoped they will do similar in humans.  Nice to see we can take advantage of viruses, since they take advantage of us so often. Important to our topic today, viruses can even take advantage of bacteria.

What a great image of a T2 bacteriophage. What
look like layers are …. layers. Each is a protein and
what is more, they self assemble! The head carries
the nucleic acid, the legs attach to the bacterium, and
the shaft creates the hole and injects the nucleic acid.

Since bacteria are prokaryotes, it would be right to assume that the viruses that infect them look and act differently than the viruses that infect eukaryotic cells. They even have a different name – bacteriophages (backtron = small rod, and phage = to feed on). Infection of a bacterium by a virus may seem a trivial event - we have our own problems to deal with. But there are several ways in which this infection affects animals.

Bacteriophages insert their nucleic acid into the bacteria from the outside; the virus doesn’t enter the cell. Similar to the bacteriocin delivery system recently discovered in bacteria, bacteriophage also use a spike system to punch a hole in the target cell. Scientists in Switzerland, Russia, and Indiana collaborated in 2011 to show that the bacteriophage spike has a single iron atom at the tip, and it punches, not drills, a hole in the target bacterium.

Once inside, the nucleic acid can have different fates. In many cases, the phage DNA is inserted into the bacterial chromosome and stays there for a while, not harming anyone, but also not making new virus particles. This is called lysogeny. Lysogens (cells infected with lysogenic phage) will then pass on the prophage (the phage nucleic acid that is integrated) on to their daughter cells.

Other bacteriophages don’t have the patience to just hang out in the bacterial genome; they take over the cell, make many copies of themselves and then destroy the bacterium by lysing it (breaking it open). These are the lytic bacteriophages.

You might recognize that lysogenic phage DNA, just sitting there in the chromosome, would die out with the cell (or daughter), so they must have another side to themselves. These phages can be lysogenic if the environment suits them, or lytic if they have the right signals, and they can switch from lysogenic to lytic if the environment changes, so they are called temperate bacteriophage. Do I have to point out that they can’t go the other direction (lytic to lysogenic); how could you insert yourself into the bacterial genome if you have already caused bacterial destruction?!

There are 19 recognized bacteriophage types (probably
more now). They have different kinds of head proteins, and
some are filamentous. Cystovirus (cytovirus) is the only
virus with RNA for a nucleic acid instead of DNA. Tectivirus
is the only phage that infects both archaea and bacteria.

There are currently 19 different classes of bacteriophage that infect bacteria and archaea. That’s a bunch of different ways that a bacterium would have to defend itself, but it can. Bacteria have several different ways to prevent bacteriophage infection. In some cases, the bacteria will produce cell wall molecules to prevent phage binding or nucleic acid injection.

In other cases, the bacteria will identify its own nucleic acid, usually by adding methyl groups to DNA. In some cases, the bacteria will methylate its own DNA, and then cut up (called restriction, this is where the restriction enzymes used in molecular biology come from) any DNA that isn't methylated. In other cases, the bacteria will methylate the incoming viral DNA and target all methylated DNA for restriction.   

Recent evidence show that bacteria even have a version of adaptive immunity. The CRISPR system takes spacer DNA (short repeats outside genes) from the bacteriophage and places them in specific CRISPR spots in its own chromosome. These serve as a memory in case that bacteriophage is encountered again. If it is, the appropriate spacer can be turned in to a piece of RNA that will target the phage DNA for destruction (called RNAi, the “i” stands for interfering, the process for another discussion).

Finally, bacteria can oppose phage by giving up. Like the apoptosis in our cells or the plant hypersensitive reaction we have discussed, bacteria can kill themselves in order to prevent themselves from becoming virus factories. In the case of bacteriophage-infected bacteria, the process is called high frequency of lysogeny. This system prevents the bacterium from carrying the prophage and passing it on to daughter cells by having the cell die before it replicates.

So bacteria infected by phage can defend themselves, but in some cases, they don’t need to. In fact, it may help them out. Consider a lysogenic phage of one type and lytic phage of another type. Which would a bacterium consider living with – certainly not the lytic phage. But many viruses, including phage have mechanisms to prevent superinfection (infection with a second virus); phage of one type cannot survive in a bacterium infected with a phage of another type. If the lysogenic phage got there first, it could actually protect the bacterium from a death by a lytic phage.

Cholera toxin is carried by the CTX bacteriophage.
The phage needs TCP, a type IV pillus to infect the
V. cholerae. Once the bacterium is growing on the
intestinal surface, the phage is activated, reproduces,
infects other bacteria, and the cholera toxin is
produced. So to cause disease, the bacteria must
undergo horizontal gene transfer to gain the pillus,
and be infected by the CTX phage.

We may chuckle at the idea of bacteria getting infected – in many cases it serves them right – but it can also affect us. Certain bacteriophages possess DNA that can make an infected bacterium even better at causing humans distress. The cholera toxin of Vibrio cholerae is carried by the CTX bacteriophage, and the diphtheria toxin gene of Cornybacterium diphtheriae is also transferred from bacterium to bacterium by a phage.

But phage may also be turned from the dark side and used to help mankind. In the spirit of our recent discussions on when it is beneficial to be infected, how about letting your doctor infect you with bacteriophage to kill off your bacterial infection?

It is no secret that antibiotic resistance is becoming a large problem in medicine. If we know that viruses can infect bacteria, why don’t we use them as a type of antibiotic? This may very well be a good idea, but it isn’t a new one.

Before the advent of penicillin and other traditional antibiotics, bacteriophages were used to treat bacterial infections in the Soviet Union and Eastern Europe. However, the 1920-30's trials were not without their flaws, mostly because scientists didn’t have a good idea of how phages worked. For many years the West remained behind, because Soviet research was not widely distributed.

To kill bacteria, lytic phages would be the tools of choice. But there is a downside, we use bacteria to stay alive. You wouldn’t want to kill of your gut flora, you need them to digest food and absorb vitamins. So, bacteriophage must be delivered to the site of the infection only, replicate there but not travel, and kill only the target bacteria. This is a tall order, but trials are in progress for bacteriophage as antibiotics against drug resistant Staphylococcus and others. Bacteriophages are even being tested in bacterially-infected plants.

The SOS system is one way a bacterium can repair
DNA damage. The damage stimulates RecA protein
function. This is an important protein. It works in
many forms of DNA repair, as well as being responsible
for homologous recombination. The SOS repair genes
are controlled by RecA degrading the protein that
represses their production. They go on to fix the DNA
problem.

On another front, research at MIT and Boston University from 2010 suggests that it may be possible to inhibit bacterial antibiotic resistance mechanisms, and once again making the resistant bacteria susceptible to conventional antibiotics. In this case, bacteriophage were engineered to target the bacterial DNA repair system in the target cells. The SOS system (see picture to right) is induced when bacteria are treated with antibiotics, but the bacteriophage-treated cells were more susceptible to the antibiotic. This could prevent resistance from developing, but may also be useful in strains that have developed some other antibiotic resistance mechanism.

Another potential bacteriophage aid to humanity has nothing to do with disease. May 2012 work from the University of California has made use of the mechanical energy of the bacteriophage inside bacteria, turning it into electrical energy (piezoelectricity, piezo = to press or squeeze). While this is a very small amount of power per cell, it is hoped that this may soon be harnessed to run your smart phone and iPad.

Next week we will start a series on heat in Biology.



Browning, C., Shneider, M., Bowman, V., Schwarzer, D., & Leiman, P. (2012). Phage Pierces the Host Cell Membrane with the Iron-Loaded Spike Structure, 20 (2), 326-339 DOI: 10.1016/j.str.2011.12.009

Lu, T., & Collins, J. (2009). Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy Proceedings of the National Academy of Sciences, 106 (12), 4629-4634 DOI: 10.1073/pnas.0800442106

 
For more information or classroom activities, see:

Bacteriophage –

phage therapy –
http://www.popsci.com/science/article/2011-04/bleaching-threatens-coral-phage-therapy-could-prevent-ghost-coral