Wednesday, June 29, 2016

Why Can’t We Just Go With the Flow? – The High Cost of Heating

Biology concepts – endothermy, ectothermy, poikilothermy, thermoregulation

So you are lying in bed, cold and hungry, contemplating living like a monk just so you can have more time to live like a monk (see this post on increasing life span via reduced core temperature and caloric restriction). Your temperature is going down after bedtime and coming back up in the early morning. This implies that you can control and maintain a constant temperature - pretty impressive. But don’t get a big head, most mammals can do it, even your pet hamster.

The hypothalamus is located in the lower center of the
brain. Different parts are involved in sensing and
regulating temperature, but also for blood pressure,
circadian rhythms, and feeling full after eating.
To be able to control your temperature (thermoregulate), you must know what your temperature is in the first place. Mammals have sensors in their skin and organs which relay information about temperature to the hypothalamus of the brain. The neural sensors in skin (peripheral thermoreceptors) sense the temperature just under the surface. This can be quite different from the core temperature. Central thermoreceptors sense the temperature in the brain, bladder and muscles. Your hypothalamus sets your skin thermostat at about 72˚C, so you still feel hot when the ambient temperature is >75˚F even though your core temperature averages 98.6˚F (37˚C).

Heat is constantly being generated by your metabolism (The breaking down and building up of molecules in your cells). Burning ATP to produce work also produces heat as a byproduct, and this goes a long way to keeping our temperature around 98.6˚F. Generating internal heat to maintain a body temperature is called endothermy (endo = within, therm = heat). Mammals are endotherms, and we hold a constant temperature, so we are also homeotherms (homeo= same). However, we have seen that constant temperature is a relative term, since our circadian rhythm cycles our core temperature up and down as the day goes on.

This is an infrared image of the human body.
Temperatures increase from blue to green to
yellow to orange to red. The head is often one
of the warmer parts of the body since the brain
uses so much energy, while the testicles are
housed outside the body to keep them cooler. 
image source:
In addition, holding a constant temperature doesn’t mean that all parts of the organism are the same temperature. Just like your skin is cooler than your core body temperature, parts of your internal body can be warmer than your average core temperature. During intense exercise, your muscle temperature can go to 107˚F or higher! On the other hand, sperm is damaged by high temperature, so the testicles are usually housed in an external pouch in order to keep their temperature one or two degrees below body temperature.

The higher than average temperature is O.K. for a short while or in a small part of the body, but if it involves too much volume or stays high for too long, then your core temperature can rise to dangerous levels (104˚F). On the other hand, having too low a temperature in any part of the human body can be dangerous. If ice crystals form in the cell, the jagged edges will cut the cell to ribbons and kill it; this is frostbite.

Your body thermoregulates to maintain a healthy temperature range. It finds ways to dissipate heat when the core temperature rises, such as sweating in humans, panting in dogs, or pushing more blood through the large ears of rabbits. If your core temperature is too low, you can generate heat by shivering (small muscle spasms that mean more ATP burned and more heat). Chattering teeth is just a spasm in the buccinator muscles of your jaw. These are pretty big muscles (bigger on some people I know) and can produce enough heat to keep your head warm.

Some endotherms are exquisitely adept at regulating the temperature in different parts of their body, and can save lots of energy through this differential regulation. Ground squirrels in hibernation reduce their abdominal temperature to match ambient temperature down to 0˚C, and some birds can hold a body temperature just one degree above freezing all night. These types of animals are referred to as endothermic poikilotherms (poikilo = varied).

Lizards are ectotherms, so they have temperatures near
ambient. In this image, the ambient temperature was
76.1 ˚F, so the lizard remains near that temperature.
However, the human hand is much warmer, as it has an
internal source of heat.
We are biased toward believing that all animals control their body temperature just because we do, but the vast majority of animals are ectotherms (ecto = outside). They get most of their heat from the environment, and this works for them.

Ectotherms like reptiles and insects will have low activity when it is cool, but absorbing heat by sunning themselves will speed them on their daily errands. This is because the rates of most cellular activities increase with temperature right up to the point of boiling, but low temperatures slow them down greatly. So most animals need an external source of heat to allow them to hunt, protect themselves, or seek shelter.

Some ectotherms, like moths and bees, can have their wing muscles go into spasms in order to generate enough heat for them to take off.  If they can raise their temperature in any way (sunning or spasming), they are called ectothermic poikilotherms, although some might call moths and bees partial endotherms, since the source of heat is internal. On the other hand, a few ectotherms like some fish, always have the same temperature as their environment no matter their activity or needs. These animals are referred to as ectothermic homeotherms.

There are many more ectotherms than endotherms in the world because it is a successful strategy for saving energy. It is extremely costly to maintain a high metabolic rate and a constant internal temperature, like running your furnace all winter to stay comfortable – we all know how expensive that can be. An adult human (endotherm) needs 1300-1800 kCal/day to maintain its temperature and activity, while a crocodile (ectotherm) of the same size requires only 60 kCal! Fewer calories needed means less energy expended hunting or foraging which makes surviving times easier when less food is available.

Even though they may be called cold-blooded, don’t assume that ectotherms are always cold.  Rimicaris exoculata, an ectothermic shrimp that lives next to hydrothermal vents (undersea volcanoes that spew superheated water), is happy with an internal temperature of 350˚C (662˚F). The water doesn’t boil because it is under so much pressure (for every 33 feet of water, the pressure doubles); otherwise they would be shrimp toast.

On the left is a deep-sea hydrothermal chimney called a black smoker. The temperature in the hot water column is near 700˚F. The right side image is the vent shrimp, Rimicaris exoculata. The bright spots are the dorsal eyespots and are rich in rhodopsin. They glow like cat’s eyes when light is shone on them. In the deep ocean, there is no light, so the
shrimp don’t glow normally.

Also don’t assume that ectotherms are looking for a way to warm up. Some fish are perfectly comfortable in antarctic waters at (-2˚C to -4˚C; the ocean water doesn’t freeze because the salt disrupts crystal formation). For example, Dissostichus mawsoni fish have proteins that help important molecules resist cold damage (heat shock proteins) and to stay functional at low temperatures (chaperonins). 

The left image shows Dissostichus mawsoni, the Antarctic toothfish,
swimming under an ice sheet. Up close, we can see the teeth, and
that he isn’t going to win any beauty contests.

D. mawsoni  also has an antifreeze protein in its blood that binds to ice crystals and keeps the fish from freezing solid. Now that’s cold-blooded. These notothenioid (notothen = “from the south” in Greek) fish are successful enough in this environment to make up 90% of the fish biomass in the Antarctic.

Unfortunately, the terms warm-blooded and cold-blooded have become popular for all organisms. This is wrong on so many levels. We think of snakes as cold-blooded, but on a hot sunny day, the internal temperature of a snake will be much higher than that of a mammal. And we already talked about birds, endotherms of the highest order, that can allow the temperature of their feet to come within a degree of freezing. Now, which is warm-blooded and which is cold blooded?

And where do these terms leave plants? They don’t have blood – so they can’t be cold-blooded or warm-blooded – but they are ectotherms. Some plants are even poikilotherms- they can generate some heat at certain points in their life cycle. They can’t maintain or regulate it, so they are still ectotherms, but let’s not be prejudiced against them by calling them cold-blooded.

Low and behold, there are exceptions to the rules of body temperature – wouldn’t you know it.  There is a plant that can maintain a constant temperature by producing heat – even if it is only for two days a year. And there is a mammal that seems to think ectothermy is the way to go. We’ll talk about these rule-breakers starting next time.

Shillito B, Le Bris N, Hourdez S, Ravaux J, Cottin D, Caprais JC, Jollivet D, & Gaill F (2006). Temperature resistance studies on the deep-sea vent shrimp Mirocaris fortunata. The Journal of experimental biology, 209 (Pt 5), 945-55 PMID: 16481583

Kiss AJ, Mirarefi AY, Ramakrishnan S, Zukoski CF, Devries AL, & Cheng CH (2004). Cold-stable eye lens crystallins of the Antarctic nototheniid toothfish Dissostichus mawsoni Norman. The Journal of experimental biology, 207 (Pt 26), 4633-49 PMID: 15579559

For more information, classroom activities, or laboratories on endothermy, ectothermy, or thermoregulation:

thermoregulation –

endothermy –

ectothermy –

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

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 –

Wednesday, June 15, 2016

Tricky Little Buggers

Biology concepts – immune defense, antibiotic resistance

Naim Süleymanoğlu is better known as Pocket
Hercules (4' 10"). He was born in Bulgaria, but is
of Turkish descent. He competed and retired
several times, and won gold medals from 1983
to 1998. He is one of the first competitors to
lift more than 2.5x his own body weight.

There was a small Turkish weightlifter a few years back whose nickname was “Pocket Hercules.” He won gold medals in three separate Olympics and was the one the best examples of big things in little packages. Last week we talked about the immune systems of vertebrates, invertebrates and plants, now let’s talk about the defenses of the smallest organisms – bacteria are the Pocket Hercules of biology.

Do bacteria have defense mechanisms? You bet – they get attacked all the time.  For bacteria that stray into or purposefully target animal or plant hosts, the perils are many and varied. Antimicrobial peptides try to burst them, antibodies try to bind them up and point them out to killer cells. Macrophages and other phagocytic cells try to eat them or wall them off from the other host cells. Organisms will even sacrifice their own cells just to make sure they kill the bacteria. It’s a jungle out there.

We don’t have the time nor the room to go into the thousands of ways that bacteria protect themselves from plant, invertebrate, and vertebrate immune attack, but we can give a few examples, like deception. Mimicry is when a bacterial antigen looks much like one of our molecules, so that the body is either fooled into not attacking, or tempers its attack.

Other bacteria change their clothes to remain hidden. Just when an immune system sees it and starts the attack, Neisseria gonorrhoeae changes its surface molecules and becomes invisible again. On the other hand, Yersinia pestis remains invisible by living inside macrophages.

Some bacteria stunt our antibody response. The best way to keep from being attacked is to not allow the host to recognize and identify you. The bacteria that cause TB inhibit our immune system from producing specific antibodies. 
Some bacteria vary the antigens they show on
their surface in order to evade the immune system.
In this bacterium, the dark areas are stained for
one particular surface antigen. You can see that
some of the cells have none of that protein, some
have only that surface protein, and some have
discrete areas where that protein is expressed.

The defense is a good offense, so some bacteria attack. Pseudomonas strains kill the phagocytic cells that would try to eat them by releasing chemicals called aggressins. Staphylococcus aureus just confuses the phagocytes, producing toxins that stop their movement or make them move erratically.

These are but a few of the many bacterial defenses against our immune system. But they have evolved defenses against other threats as well, like our attempts to kill them with antibiotics.

We talked earlier about multidrug efflux pumps in bacteria that pump out the antibiotics with which we try to kill them. This is related to the stories in the media about antibiotic resistance in bacterial pathogens, but classic antibiotic resistance genes are often plasmid based defenses, as we have discussed. Recently, an additional defense against antibiotics has been recognized.

It seems most bacteria produce hydrogen sulfide (H2S, smells like rotten eggs), which was previously thought to be only a metabolic byproduct. A late 2011 study shows that H2S is part of an integrated defense system used by almost all bacteria. The gas works to prevent oxidative damage. This is not unheard of since a few bacteria produce nitric oxide to do the same thing, but it is being recognized now that oxidative stress induction is a big part of how many antibiotics work. When the H2S system was turned off in several pathogens, they became much more sensitive to antibiotics. Maybe this a lesson we can exploit in the future.

In addition to our attempts to kill them, the universe itself is a tough place to survive if you are a bacterium. They may end up in bright sunlight for long periods of time, or hurtling through space on a rocket or meteor. Bacteria have ways to protect themselves here as well. Ultraviolet radiation from the sun is a mutagen (causes mutations in DNA), but it also can break down cellular molecules to release oxygen radicals, like hydrogen peroxide or superoxide.

It has been known since the 1950’s that pyruvate and catalase, as well as the newly discovered H2S discussed above, do some work in protecting the cell against oxidative damage, but a 2009 study described a whole new mechanism. It seems that E. coli has two proteins that seek out, identify, and repair oxygen radical-mediated damage to sulphur-containing cysteine amino acids within proteins.

Cysteine is the most reactive of the 20 common amino acids, which means that it are often located in the functional site of enzymes (where the enzyme reacts with the substrate). However, this reactivity also makes cysteine vulnerable to reaction with radicals, especially oxygen radicals, after which it becomes modified and non-functional.

Disulphide bonds are formed between adjacent cysteines on the 
same peptide, far apart cysteines on the same peptides, 
or between cysteines on different peptides. When 
you (not me) get a permanent wave for your hair, the 
disulphide bonds are broken or rearranged by a reducing agent. 
To prevent this radical-mediated damage, cysteines often occur in pairs, where links between the sulphurs of the two cysteines help to prevent oxidation (called disulfide bonds, they also serve to link peptides together and give proteins their proper form). A 2008 study showed that this mechanism provides unusual oxidative stability to a cysteine-containing enzyme of the bacterium, Desulfovibrio africanus.

But there are exceptions; lone cysteines do occur, and these are the cysteines most vulnerable to oxidative damage. The DsbG and DsbC proteins of E. coli patrol the cytoplasm looking for oxidized cysteines to fix.

Here is how ingenious the system is – oxidizing a cysteine may or may not unfold the protein, so DSbG is charged and can interact with the still-folded proteins to correct the cysteine problem, but DsbC is uncharged, so it works better with proteins that have been unfolded. Amazing - and bacteria developed it all on their own – well, with the help of the evolutionary pressure of things trying to kill them.

I mentioned that radiation is also a DNA mutagen. The mutagenic properties of radiation affect bacteria just like they affect us; it is just that some bacteria can protect themselves better once their DNA is damaged. Follow me closely here - by using protein repair and protection systems, bacteria like E. coli, with its DsbG and C enzymes, can keep protein functions going when other organisms would break down and die. Some of these protein functions include DNA repair after mutagenesis. So - some bacteria don’t survive radiation because they protect their DNA better, they survive because they repair the damage better.
This is an overlap of different types of images of a
radiodurans bacterium. The circles of blue green and
pink show high concentrations of manganese, while
red is iron. The manganese is clustered around the
DNA and works to repair it after radiation damage.

Other bacteria have a different mechanism to maintain protein function. According to a 2010 study, a shield of manganese metal atoms and phosphates was found in D. radiodurans. It had been long known that manganese was present in very high levels in bacteria that are most resistant to radiation, but its function was unknown.

The recent study shows that these manganese complexes work together to protect proteins from radiation damage, but not DNA. The key for this system is to keep proteins functioning, which can then repair any radiation damage to the DNA. This mechanism allows D. radiodurans to withstand prolonged radiation that is 1000x stronger than that which would kill a human.

So, bacteria have defenses against immune and environmental attacks. Does anything else attack bacteria? How about other bacteria - it’s dog eat dog out there, competition for resources is brutal. Many bacteria have poisons (bacteriocins) that inhibit or kill bacteria that are distantly related (because related types of bacteria are likely to be in the same places looking for the same food). 

One type of bacteriocin are the lantibiotics. These protein toxins contain a nonstandard amino acid, called lanthionine. We mentioned above that cysteines are very reactive; lanthionine is a modified circular (polycylic) cysteine that gives the toxin its reactivity. And because it is cyclic, it is much less vulnerable to oxidative damage itself – funny how bacteria seem to cover their bases so well.

This is so cool. Bacteria that are engineered to produce
light were injected into rats. The rat in the middle was
also given a bacterium producing a bacteriocin to the
light producing bacteria. The whole rat bodies were
imaged while they were still alive to see if the bacteria
were alive and reproducing. Live animal imaging is a
great tool that is becoming more popular. Image by S.
C. Corr and P. G. Casey.
Lantibiotics come in two types, they either form pores in Gram+ bacterial cell walls or inhibit the cell wall formation. Because they attack only specific types of bacteria, lantibiotics are useful in cheese-making; they allow some bacteria to grow and ripen the cheese, while killing those that would cause the cheese to spoil. One type B lantibiotic just came through its phase I clinical trial in July 2012 with flying colors (phase I trials are meant only to test safety, not effectiveness).

A recent discovery illustrates just how bacteriocins are delivered to the target organism. It seems that bacteria can build a spike and a spike launching system anywhere on their cell membrane. The spike is spring loaded in a tube just 80 atoms long, and is fired at the target cell. Then the bacteriocin is released at the end of the spike to do its damage.

The release of toxin was already known, called a type IV secretion system, but the CalTech study that identified the spring-loaded spike as the delivery system is very new. Once fired, the whole system is broken down, ready to be rebuilt somewhere else in the cell. Amazing. (click for video)

Of course, for every punch there is an evolutionary counterpunch, so there are bacteriocin resistance mechanisms as well. Nisin, a bacteriocin active against strains of listeria, is approved as a food preservative. But listeria can spontaneously develop resistance to nisin. It appears that some strains change their membrane chemistry in order to render nisin ineffective. Therefore resistance could be a problem if we pursue the use of bacteriocins as antibiotics; we might end up back in the same situation that we're in now.

Regardless of this possible downside, scientists have found a way to bring bacteriocins into the battle against antibiotic resistance. An E. coli has been engineered to contain the gene for pyocin, a bacteriocin that kills strains of Pseudomonas bacteria. E.coli and Pseudomonas are not closely related, so E. coli would not naturally possess this toxin, scientists added the gene to the E. coli.

This is schematic of the engineered bacteria to kill Pseudomonas.
P. aeruginosa make chemicals when their numbers reach a
certain density. These trigger pyocin production in the E. coli,
but also triggers the production of the protein that lyses the
E. coli. When lysed, the pyocin attacks the P. aeruginosa.
When the engineered bacteria encounters Pseudomonas, it does two things; it produces the pyocin toxin to kill the target cell, and the engineered E. coli commits suicide. No release system has been engineered into the E. coli, so the only way they get the pyocin to the target is to have the E. coli produce a lysin that destroys its own cell membrane.

This suicide accomplishes two things, it releases the pyocin to kill the target, and it prevents the engineered E. coli from hanging around forever, possibly trading genes with other bacteria or causing havoc in some unforeseen way.

So it looks like bacteria have it made. They can resist immune system attacks, some can resist environmental onslaughts, they even have ways to protect themselves against competition and threats from other bacteria. No wonder they have always been the predominate life form on Earth. But bacteria do have foes of considerable power – veritable “Micro-Hercules” – we will meet them after Thanksgiving.

Let’s take a couple weeks to talk about the biology of turkeys and the so-called “tryptophan nap.”

Basler, M., Pilhofer, M., Henderson, G., Jensen, G., & Mekalanos, J. (2012). Type VI secretion requires a dynamic contractile phage tail-like structure Nature, 483 (7388), 182-186 DOI: 10.1038/nature10846

Saeidi, N., Wong, C., Lo, T., Nguyen, H., Ling, H., Leong, S., Poh, C., & Chang, M. (2011). Engineering microbes to sense and eradicate Pseudomonas aeruginosa, a human pathogen Molecular Systems Biology, 7 DOI: 10.1038/msb.2011.55

For more information or classroom activities, see:

Bacterial defenses–

Bacteriocins –
see Pubmed ( for more information on these defenses.