Those bacteria that call your gut their home are the so-called commensal bacteria. Luckily, they have a special superpower: They can protect us from bacteria that cause infections and make us sick. For this, our commensal gut bacteria developed some extraordinary strategies to defend these pathogens.

So, by nurturing our friendly gut bacteria, you are also strengthening your protection against diseases. Here, we will look at what kind of bacterial wars are going on in your gut and how your gut bacteria defend pathogens and keep you healthy.

Your gut bacteria defend pathogens with toxic molecules

Bacteria have many different means to kill other microbes, competitors or even their own siblings. Often, these bacteria produce molecules that are toxic to their prey, which means they inhibit cellular proteins or machineries. Without these machineries, the prey is then lacking an essential cell function to grow or survive, so that it eventually dies.

Interestingly, gut bacteria produce and deliver many different toxic molecules of various shapes and sizes, functions and even origins.

Gut bacteria produce bacteriocins

Many bacteria produce molecules that are like antibiotics specifically to kill bacteria. These are called bacteriocins.

Some bacteriocins are simple and small molecules, while others can be big and fancy. However, they all have a similar goal: they bind to a specific target in the prey bacterium and prevent that target from working properly.

So, no wonder that many bacteria in our gut microbiome produce bacteriocins that are toxic to pathogenic intruders. Also, we carry a lot of different bacteria in our guts and they all produce different bacteriocins. Hence, incoming pathogens face this huge load of toxic molecules making it really difficult to establish themselves in our intestines.

For example, one bacterium that loves the warmth and lack of oxygen in our gut is the bacterium Ruminococcus gnavus. And this one produces at least two bacteriocins, Ruminococcin A and C, that are toxic against human gut pathogens like Clostridium perfringens.

Other friendly gut bacteria, like Escherichia coli or Blautia producta, also produce bacteriocins that are toxic to pathogens, like Enterococcus faecalis. And some of their bacteriocins can even impact our gut cells by activating and strengthening our immune response.

Gut bacteria produce short chain fatty acids from fibres

Another way to protect against pathogenic gut bacteria is directly related to your diet. When we eat a lot of fibres, which are non-digestible carbohydrates, our friendly gut bacteria break these up. From these fibres, they produce small molecules that are called short-chain fatty acids, which have many positive health benefits for our overall wellbeing.

Interestingly, when we have a lot of these short-chain fatty acids in our intestine, the pH drops. This is already pretty difficult for most pathogenic bacteria, as not many can handle this acidic environment.

Plus, short-chain fatty acids diffuse into pathogenic gut bacteria where the pH drops as well. This can disturb many cellular machineries from functioning properly and not many bacteria have the right tools to defend against this attack, so they’ll die.

Gut bacteria convert bile acids into toxic compounds

To better digest the fats in food, our liver produces bile acids. These molecules bind fatty acids and lipids so that we can take them up better into our bodies.

But some of our friendly gut bacteria can convert these primary bile acids from our liver. For example, one of these bacteria, Clostridium scindens, transforms them into secondary bile acids that can bind the lipids of bacterial membranes.

Like this, secondary bile acids open the membranes of some pathogenic gut bacteria, like Staphylococcus aureus, Bacteroides thetaiotaomicron or Clostridoides difficile. This eventually kills the intruders and keeps our guts pathogen-free.

Killing pathogens with bow and arrow

Yes, also direct bacterial wars are happening in our guts! And they are nasty!

Some bacteria use tiny little bows to shoot deadly arrows into other bacteria. And these arrows can be incredibly toxic so the shot bacterium has barely any chance to survive the attack.

Luckily, our gut bacteria use their bows and arrows to defend against gut pathogens. For example, commensal bacterium Bacteroides fragilis has three different bows and can shoot various arrows. And research showed that this bacterial friend can protect us from bacteria that otherwise cause intestinal diseases.

Interestingly, Bacteroides fragilis is not opposed to hit’n’kill its own toxic bacterial siblings since some members of his family can indeed make us sick. But our friendly Bacteroides fragilis collected many different immunity proteins against its evil siblings so that their toxic arrows cannot harm it. Instead, Bacteroides fragilis keeps shooting and killing until we are safe from the pathogenic sibling.

Keeping nutrients from pathogenic gut bacteria

Another important way how gut bacteria defend pathogens is by keeping nutrients away from them. In all mixed microbial communities, bacteria fight for nutrients, especially for metals like iron, zinc but also sulphur sources.

Luckily, our gut bacteria developed some sneaky ways to steal these metals from gut pathogenic bacteria. By sending out special proteins that bind these metals very tightly, the commensals make sure to keep these metals from the pathogens. And if the pathogenic bacteria don’t have enough of these essential metals, they won’t survive and will eventually die.

Strengthening the mucus layer to block pathogenic gut bacteria

When you think about it, your gut is not part of your body – even though it is inside of you. All the food that we eat, stays within this digestion tube (mouth, oesophagus, stomach, intestines) until it comes out on the other side.

And to protect us from harmful microbes and molecules, we need to have a clear physical barrier from the content of the tube. This barrier is the so-called epithelial layer, which is covered by a slimy mucus on the outside. And this sticky slime helps keep off intruding microbes so that they cannot breach through the epithelial wall and get into our bodies.

Luckily, our helpful gut bacteria help us maintain this slimy defence wall. As bacteria produce SCFAs close to the mucus layer, the epithelial wall produces more slime. And if the slime gets thicker, gut pathogenic bacteria have more difficulties getting into our bodies.

To help the slime grow, some bacteria adapted very well to the conditions within the gut. For example, the friendly gut bacteria Akkermansia muciniphila and Ruminococcus gnavus cut off the very end of the mucus layer and feed themselves with them. This does not harm the mucus itself, but it keeps these bacteria close by. And this in turn triggers the epithelial wall to produce more mucus. So, everyone wins.

How to help your gut bacteria defend pathogens

Now, that you better understand how your gut microbiome defends pathogenic gut bacteria, make sure you support them keeping you healthy. By feeding your gut bacteria the right foods, you will help them be comfortable and happy in your gut. And when the right bacteria grow within you, they will gratefully protect you from nasty intruders!

Another idea for researchers is to use what they have learned to keep you healthy. The idea is to develop probiotics or prebiotics that help us defend against nasty pathogens. For example, you might take pills containing toxins against pathogenic gut bacteria or probiotics with bacteria that can fight off pathogens.

Whatever it may be, you can always help your gut bacteria be happy in your intestines by eating the right things. That means lots of fibre and veggies! ?

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And more and more people become aware that a plant-based diet is not only better for your health, but also for our planet. Hence, the focus on agriculture right now is to become more sustainable to grow enough plant-based food for everyone.

This means that we need to find better ways to support plant growth and protect plants from diseases. Unfortunately, several plants pathogens make plants sick, so they die or do not grow enough crops.

Currently, we use fertilizers and pesticides to protect plants from pathogens. However, these chemicals are bad for the environment long-term as they contaminate the soil and water.

Hence, we need to find ways to protect plants by either getting rid of dangerous intruders or by strengthening the immune systems of plants.

Enter bacteria and their superpowers.

They do both.

What is biocontrol?

Some bacteria that live in or on plants are called biocontrol agents. These organisms are harmless to the plant and have two main functions: They protect the plant from pests and diseases and support its growth and crops.

Some of these organisms additionally strengthen the plant’s immune system or resistance – again to protect the plant from disease and help it grow.

One such biocontrol agent is the bacterium Pseudomonas putida. It grows near the roots of many plants where it produces helpful molecules for the plant.

And plants are clever too as they make sure that only the right types of bacteria grow near them. For this, several plants release specific molecules through their roots that help Pseudomonas putida grow. The bacterium senses these molecules so that they activate the bacterium’s chemotaxis system.

Now, Pseudomonas putida uses its flagellum to swim towards these molecules. This movement ultimately leads the bacterium to the plant that released the molecules.

Pseudomonas putida as a biocontrol agent

Once the bacterium “found” the plant, it settles down near it and starts building biofilms. Within these biofilms, the bacteria are connected with each other and with the plant. Like this, they can easily exchange molecules and information with each other and with the plant and build close relationships.

Pseudomonas putida now produces molecules to help the plant grow. For example, some molecules extend the tips of the roots so that the plant can better take up nutrients from the soil.

Pseudomonas putida also breaks down complex nutrients in the soil that the plant use. This basically feeds the plant the needed nutrients. Other molecules from the bacterium activate the overall immune system of plants so that plant pathogens have a harder time infecting the plant.

Altogether, Pseudomonas putida has similar features as biofertilizers that help plants grow.

How does bacterial biocontrol protect plants against intruders?

Pseudomonas putida can also directly fight off plant pathogens to protect their plant hosts. For this, it uses two strategies: It either holds back essential nutrients from plant pathogens or kills the intruder.

Not sure which strategy is more evil though…

Pseudomonas putida keeps essential nutrients to inhibit plant pathogens

All living organisms need iron to live and grow. And one efficient strategy to prevent other microbes from growing is by stealing iron from them.

Our immune system does it as well: All iron in our body is bound to specific transporters. Like this, no free iron swims in our blood for microbes to use. This defence mechanism is one of the first strategies of our immune systems to keep harmful bacteria from growing inside our bodies.

Similarly, Pseudomonas putida produces many different iron transporters that bind iron very efficiently. Like this, no free iron is present in the soil that other microbes could use.

Yet, this is not all. Pseudomonas putida is quite a naughty one since it can also steal iron-loaded transporters from other bacteria. This not only prevents the other bacteria from using the iron, but it also helps Pseudomonas putida grow.

Pseudomonas putida kills intruding plant pathogens

Lastly, Pseudomonas putida is a real fighter when it comes to protecting its host plant. This bacterium uses a special nanoweapon to kill plant pathogens.

Our bacterial fighter carries a bow and arrow and is not afraid of using them to keep intruders off the plant. Pseudomonas putida actively shoots arrows together with lethal toxins into other bacteria to kill them. Many bacteria use this killer machine, called the type 6 secretion system. But interestingly, Pseudomonas putida seems to have a more efficient killing device than others.

Scientists proved that with a simple experiment. When different plant pathogens were growing inside plant leaves, the leaves got sick. However, when Pseudomonas putida was additionally living in the leaves, the plant leaves did not get sick.

Finally, the scientists let the plant pathogens grow together with a Pseudomonas putida bacterium that could not shoot its bow and arrow. Now, the plant leaves got sick again and the plants suffered from the plant pathogens.

These results show that Pseudomonas putida uses its bow and arrow to actively kill other harmful bacteria to protect plants. Even though the experiment was done in plant leaves, scientists are convinced that something similar happens in the root area of plants.

Bacteria as biocontrol agent to save our planet?

As soon as we better understand how exactly this plant warden protects its host from harmful bacteria, we could use Pseudomonas putida on a large scale. This would improve the health of plants so that they can grow more and better crops.

Hence, such a biocontrol agent would eventually help us have more food available for everyone.

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Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

But what do bacteria and fungi use antibiotics for? Why do they produce them? And what are the advantages of microbes having antibiotics as molecular weapons?

What are antibiotics?

The father of antibiotics, Selman Waksman, first used the word antibiotics for any small molecule made by a microbe that can inhibit the growth of other microbes.

So, microbes – especially bacteria and fungi – use antibiotics to kill other microbes. These other microbes can be bacteria, fungi or bigger organisms. Not viruses though!!!

Why not viruses?

Because antibiotics bind and inhibit cellular machines in living organisms. These molecules often bind to so-called targets. Antibiotic targets can be proteins or enzymes that make for example the cell wall, other proteins or components of the respiration complex.

These proteins are generally essential. So, when antibiotics inhibit the proteins, the cells are missing these essential functions. And without them, they cannot survive and die.

Hence, like other bacterial toxins, antibiotics are lethal.

Interestingly though, bacteria and fungi make antibiotics from simple building blocks. These are present in every cell and can be amino acids, lipids or even sugars.

But instead of using these building blocks for their normal functions, microbes link them together in different ways. With this, they create new – and fancier – molecules that barely resemble the original blocks.

Then, they transport these antibiotics to the outside or send them off in outer membrane vesicles. When the antibiotic hits another microbe, there are two possibilities: either the microbe is resistant to the activity of the antibiotic or it dies from it.

But what about the microbe that produces the antibiotic? Is it resistant to the antibiotic itself?

Why are microbes that produce antibiotics not get killed?

Since antibiotics are meant to KILL other microbes, then why do producing microbes not get killed by their own antibiotics? The answer is self-protection!

Whenever bacteria or fungi produce antibiotics, they always also produce some sort of self-protective means. Just as when bacteria produce other toxins, they always need to make sure they are not killed by their own weapons.

These self-protectors usually keep the antibiotic in an inactive state. For example, they completely surround the antibiotic molecule so that it cannot bind to its usual target within the cell. Another strategy is to add a small molecule to the antibiotic – again to keep it from binding to its target.

Then, when the microbe is ready to transport the antibiotic outside of the cell, it takes the self-protection off the antibiotic. This releases only the toxic part – the antibiotic itself – into the surrounding.

Note, however, that these self-protection mechanisms are not antibiotic resistance mechanisms. Self-protection mechanisms are meant to inactive antibiotics only temporarily. Hence, these mechanisms are reversible. The antibiotic can still become active and thus toxic.

Resistance mechanisms, on the other hand, are meant to inactive antibiotics permanently. Hence, these mechanisms are irreversible. Since this usually completely destroys the antibiotic, it cannot become active anymore.

But what triggers microbes and especially bacteria to produce antibiotics? How do antibiotics help the producing cell in their daily circumstances?

Why do bacteria produce antibiotics?

To answer this question, we need to look at where the bacteria live that make antibiotics. And two-thirds of the known antibiotics are made by bacteria from the Actinobacteria family. Within this family, Streptomyces is the best-known member that produces half of all known antibiotics.

Another example is bacteria from the Myxococcus family. So, where do Streptomyces and Myxococcus bacteria live? Interestingly, these bacteria call the soil their home.

And in the soil, they often confront lots of friends and foes. And they need to constantly fight for their own survival.

Myxococcus is known as a wolf-pack predator because it kills its prey in massive attacks. Colonies of Myxococcous roll over their prey, secrete antibiotics and thus kill them and feed on them.

Streptomyces, on the other hand, uses its antibiotics a bit more civil.

To move in the environment, Streptomyces bacteria grow as long filaments throughout the soil. They build long chains and branch out into the soil as multicellular organisms. These branches are filled with Streptomyces cells but also spores so that the bacteria can extend to new places.

When the bacteria hit a period of bad weather or don’t find much food, they release their spores as a survival strategy. Plus, they start releasing nutrients for the spores. But these nutrients also attract other organisms like bacteria.

Hence, at the same time, Streptomyces produces a huge amount of antibiotics to fend off these putative food-stealers. Like this, Streptomyces makes sure their spores are safe and can survive in their new homes for a while.

How do antibiotics produced by bacteria help others?

Like Streptomyces, lots of bacteria use antibiotics to fight off predators. This assures their own survival and that of their species.

Yet, more and more research finds that bacteria not only kill other species with antibiotics so they can survive. The killing also benefits their hosts.

For example, the bacterium Janthinobacterium lividum lives on frogs where it produces the antibiotic violacein. This antibiotic kills fungi so that the bacterium protects the frog from deadly fungal infections.

Also, a bacterium that lives in our noses is the harmless Staphylococcus lugdunensis. This bacterium produces the antibiotic lugdunin. That inhibits the harmful Staphylococcus aureus from settling down in our noses. Now, scientists look into how we could use the harmless Staphylococcus lugdunensis to protect us from infections.

Another example of microbes that produce antibiotics to help others is the three-member association of ants, Streptomyces and a fungus. Several species of ants grow fungi for food. They feed their fungi with fresh plants and let them grow in special underground gardens.

To not contaminate these fungal gardens, ants carry symbiotic Streptomyces that produce antibiotics. Like this, the antibiotics kill other microbes and keep the fungal gardens free of harmful intruders. As a thank you, the ants feed the Streptomyces and give them a place to live.

About antibiotic-producing microbes

So, just as we use antibiotics to kill harmful bacteria and fungi, antibiotic-producing microbes do the same. They want to fight off predators and assure their own survival.

When you think about it: we use their own killer weapons against them. Poor microbes!

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Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

And looking at these bacterial siblings can help researchers understand the basic mechanisms of the bacterial world.

For example, some bacterial families contain both pathogenic and non-pathogenic bacteria. Pathogenic bacteria are those, that have weapons to infect us and make us sick.

On the contrary, non-pathogenic bacteria are harmless to us since they do not have these weapons.

But to fight off the dangerous bacteria, we still need to better understand what turns a harmless bacterium into a nasty one. Thus, researchers are trying to learn more about the differences between pathogenic and non-pathogenic bacteria.

So, what is better than looking at bacterial siblings that are both pathogenic and non-pathogenic. They often carry the same or similar genes. And yet, they have different weapons and some of these harm us while others don’t.

One interesting example of a bacterial family with diverse siblings is Vibrio cholerae.

Vibrio cholerae and its good and bad bacterial siblings

Bacteria from the Vibrio cholerae family live on zooplankton and shellfish in brackish waters. Every once in a while, we come into contact with such a bacterium when we eat seafood or drink contaminated water. And unfortunately, some siblings of the Vibrio cholerae family can cause very dangerous and even life-threatening diarrhoea. These are the pathogenic siblings.

But interestingly, not all bacterial siblings can infect our gastrointestinal tract. These non-pathogenic siblings do not have the right tools to infect and harm us.

Therefore, researchers have been curious about what distinguishes these pathogenic and non-pathogenic siblings.

All these siblings – pathogenic or non-pathogenic – have one killer machine in common. They use a bow to fire toxic arrows into prey cells. And these cells can be bacteria, amoebae or even human cells.

Yet, within the Vibrio cholera family, not every sibling has the same set of arrows and cannot fight the same target. Hence, researchers assumed that these different sets of arrows would give the siblings the skills to become a pathogen or not.

Vibrio cholerae siblings fight off amoebae with bow and arrow

Researchers looked at five siblings from the Vibrio cholerae family and their fighting behaviour. Let’s call these siblings Pan, Ariel, Bobby, Chris and Danny.

These five bacterial siblings all have the same bows. Yet, they have different arrows that give them different fighting powers.

So, the five siblings use these arrows to defend themselves against enemies in the environment, other bacteria or even their own siblings. Some of these enemies are even bigger microorganisms like amoebae.

These amoebae are like human immune cells. They hunt and eat bacteria in similar ways.

Hence, some Vibrio cholerae siblings use their bows and arrows to protect themselves from amoebae. For example, the siblings Chris and Danny have arrows that they fire into the amoebae. These arrows have toxic bullets attached to them so that they can kill the amoebae.

Ariel and Bobby have the same kind of arrows, but these do not carry the toxic bullets. Since Ariel and Bobby cannot kill amoebae, researchers suggested that only Chris and Danny use their toxic arrows to protect themselves from amoebae.

In comparison, Pan has the same arrow and the same toxic bullets. But Pan’s bow is not active. It only gets activated under certain circumstances. Hence, when Pan faces an amoeba, it gets eaten even though it has the weapon to defend itself. Poor Pan.

Vibrio cholerae siblings kill bacterial opponents with bow and arrow

Next, their different arrows also help our bacterial siblings when facing bacterial enemies. All siblings react and defend themselves in different ways.

Since Pan’s bow is inactive, it cannot fight off bacterial enemies. Even though it has many strong arrows. It just does not fire them.

The other siblings, however, know how to use their bows and arrows. And since their arrows deliver different toxic bullets, they kill with different efficiencies.

It becomes more interesting when these siblings fight each other. In these family fights, the toxic bullets make the difference.

For example, the four siblings Ariel, Bobby, Chris and Danny can all kill off Pan easily. This is because Pan does not have an active bow, so it would not fire any arrows. Pan does not stand a chance against its siblings.

Ariel has very toxic bullets. And it does not hesitate to fire them into its siblings to kill them.

Not Bobby. Bobby struggles with fighting off other bacteria as well as its siblings. Hence, researchers suggest that Bobby’s arrows and bullets are less toxic and thus less efficient to kill.

These types of experiments help researchers understand how bacterial siblings are immune to each other’s attacks. And it gives them some clues about what makes a toxic truly efficient.

Different powers give bacteria different advantages

Just as your special skills give you great opportunities or advantages in life, bacteria use their fighting powers to survive and thrive. They learned how to defend themselves against enemies of all kinds and families. And some of them seem to have more or less efficient ways to achieve this.

So, by learning about the defence mechanisms of bacteria, we might be able to find new and better ways to fight off the nasty bacteria ourselves. Let’s hope that one day we can fight them with their own weapons.

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Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

They need food, more space and are just annoyed by intruding competitors.

So, when they decide to bring out the big (tiny) killer machines, they aim to hurt their opponents badly.

One of these killer weapons is the so-called type 6 secretion system. It looks like a crossbow that sits within a bacterial cell waiting to fire lethal arrows.

And these arrows are the real deal in this killer weapon. They punch holes into the membrane of the opposing microbes and carry lethal toxins into the cell.

Here, we will focus on these arrows and how they work.

Bacteria fire lethal spikes to kill

This type 6 secretion system crossbow is made up of two parts. One part – the base – stays within the firing bacterium. You can understand this as a stem inside the bacterium.

On top of this stem sits the second part – the arrow. This arrow is ready to be fired and will actually leave the bacterium. It consists of three parts, that you can also see in the picture below:

Such an arrow has a long thin spike (red) that is connected to the stem (black). Onto this spike, different toxins (purple) are glued and hang around the arrow. On the top of the spike, the arrow has a pointy tip (pink) that pokes the membrane of the prey bacterium.

So, when bacteria shoot these type 6 secretion system arrows into other bacteria, they shoot all these different parts: the tips, the spikes and the toxins. And the toxins are what ultimately kill the prey bacteria.

Now, bacteria actually have several different proteins for these parts of the arrow lying around in their cells. And for long, it was not clear how bacteria decide how to assemble such an arrow. So, different studies looked at these different parts and how they interact with each other to better understand how bacteria build their lethal arrows.

Let’s start at the top.

A master hat protein decides for the assembly of the arrow

The protein at the very end of the arrow is called the PAAR protein. It is very sharp and has the shape of a hat. The bacterium uses this pointy end to punch a hole into the prey bacterium’s membrane.

Our bacterium of interest, Pseudomonas aeruginosa, contains seven of these hat PAAR proteins and ten different spike proteins. Generally, one PAAR protein sits on the top of one arrow spike while the spike is actually made of three VgrG proteins. So, one study looked at which of these pointy PAAR proteins belongs to which arrow spike.

To do this, researchers made different versions of the same bacterium – so-called mutants. These did not have certain hat proteins anymore so they could not kill their opponents that efficiently anymore. Also, these bacteria were unable to fire their arrows in the first place.

With these experiments, the researchers could then identify the different hat-spike pairs in Pseudomonas aeruginosa. They also learned that the PAAR protein actually determines which arrow the bacterium will fire next.

Lethal toxins stick to the spike protein

Next, the spike proteins are incredibly important since they carry the different toxins into the prey cell. And for a toxin to stick to a spike, they both have specific patches. And these patches are unique for each spike-toxin pair.

Researchers showed this by swapping the patches for the toxins between different spike proteins. They looked at the spikes G4b and G5 in the bacterium Pseudomonas aeruginosa. Usually, the G4b spike has a patch for the toxin A and the G5 spike has a patch for the toxin B.

So, Pseudomonas aeruginosa uses spike G4b to kill with toxin A and if it feels like killing with toxin B, it shoots spike G5.

The researchers then interchanged those patches. Now the G4b spike had the patch for toxin B and the G5 spike the patch for toxin A. And they showed that G4b could not fire toxin A anymore and G5 could not fire toxin B anymore.

Instead, Pseudomonas aeruginosa now fired toxin B with the G4b spike and toxin A with the G5 spike.

This helped the scientists better understand how bacteria shoot their toxins out of the cell. Another study then looked at how this patch works and how exactly the toxin is glued to the type 6 secretion system spike.

Bacteria can (sometimes!) fire spikes with random stuff

Other studies then look at whether bacteria could use random toxins and glue them to the type 6 secretion system spikes. This idea might give us tools to shoot whatever we want with this killer machine. However, in practice, it is a bit tricky.

So, researchers tried different versions of this concept in the bacterium Pseudomonas aeruginosa.

First, they took a toxin from the same bacterium but from a different part to the arrow. Instead, they glued this toxin to the spike of the bacterium and looked at whether it would fire an arrow with this toxin. Indeed, the bacterium could now shoot this new arrow into other bacteria, even though it was not as efficiently.

In a second try, they tried to patch a toxin from a different bacterium to the spike in Pseudomonas aeruginosa. This new arrow was not able to shoot that toxin into other bacteria. So, there are some limitations about how the spikes and their patches work to make toxins stick.

Understanding bacteria and their spikes for new strategies

This bacterial nanoweapon is an incredibly handy tool for bacteria. They can deliver lethal proteins into almost any organism. If we managed to understand this weapon better, we might be able to modify it and deliver whatever we want with this.

We might be able to transport therapeutics, drugs or even anti-cancerous agents. But until we’re there, still quite a bit of research is needed.

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Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

They have killer weapons to deliver lethal toxins into other microbes.

And by killing their surrounding competitors, they make space for themselves.

Like this, they conquer new places and environments wherever they go.

But some bacteria are even more sneaky than that. They don’t kill bacteria directly. Rather, they destroy the houses that bacteria live in.

This leaves the prey exposed to the harsh environment. And the attacker can claim the now available space.

Where do these kinds of battles happen? According to researchers, they might even happen in or on our bodies.

Let’s have a look at how bacteria fight by destroying each other’s houses.

Bacteria build biofilm houses

Just like us, when bacteria feel comfortable in a place, they start building houses to settle down. They grow within these houses, multiply, invite their neighbours and become social.

A happy life.

One bacterium that is a master in biofilm house building is the Escherichia coli UPEC. This pathogenic bacterium can grow in the urinary tracts of people and cause nasty bladder infections.

In bladders or on catheters, UPEC can also build biofilms. Here, it wraps itself into a thick layer of slime to protect itself from the surrounding. In this biofilm house, no molecules, like antibiotics, or other bacteria can harm UPEC.

It seems to be protected from almost any attack.

Almost.

Bacteria fight microscopic battles

Now, researchers found that even UPEC has bacterial competitors. These live in similar places like UPEC, so they already know each other.

That’s why UPEC’s opponents came up with a special strategy to make UPEC miserable. They learned to destroy UPEC’s biofilm houses. This is meant to weaken UPEC so that other antibacterial factors now have an effect.

What does that mean?

The UPEC bacterium is pretty nasty for us since we need high doses of antibiotics to get rid of it. And we know that taking antibiotics is not a good thing. So, researchers are looking for new weapons to fight this bacterium.

The idea is that if we understand how other bacteria fight UPEC, we could learn from them. Maybe we could work out similar ways to fight UPEC.

Bacteria fight by destroying biofilms

Researchers found that some bacteria produce compounds that stop UPEC from producing biofilm. One of these attackers is Salmonella enterica Typhimurium. This bacterium even developed a strategy to exclude UPEC from its own biofilm house.

Researchers showed that Salmonella produces a toxic sugar that inhibits UPEC from forming a biofilm. Like this, Salmonella directly stops UPEC from colonising new spaces.

Another bacterium, Lactobacillus acidophilus, produces a similar sugar. Researchers showed that this toxin also stops UPEC from building a biofilm.

However, it is still not clear how these sugars exactly work to inhibit biofilm production.

Bacteria fight by producing biofilm

The researchers also found that Salmonella and UPEC did not grow well together. Separated from each other, they were happy. Together, they were just fighting.

But something else was interesting: In a mixed biofilm, Salmonella managed to outgrow UPEC. It was growing faster and produced a lot more biofilm than UPEC.

This could mean that Salmonella tries to suffocate UPEC with biofilm. The researchers thought that the Salmonella bacteria grow on top of the biofilm, where they have more oxygen. Like this, the UPEC bacteria would be buried by all this biofilm slime and get less oxygen and eventually die.

Surely not a nice way to go!

What can we learn from these bacterial battles?

This study told us a lot about how bacteria live together and fight each other. Researchers are constantly looking for new ways to kill those bacteria that we cannot fight with antibiotics anymore. Based on this, we can even use bacteria as biocontrol agents to fight other pathogenic bacteria.

For example, Salmonella produces a compound that stops UPEC from forming biofilms. If we better understand how this toxin works, we might have a new method to inhibit bacteria from colonising surfaces in hospitals.

Also, UPEC and Salmonella are pathogenic bacteria and they can survive in wastewater even after cleaning. This is a major health issue. Hence, finding new ways to fight these bacteria will help us live healthier and safer.

This study was a small step in the grand fight against superbug bacteria. But those small steps are often the most important ones.

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Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

One of these killer weapons is the so-called type 6 secretion system.

Bacteria use this nanoweapon like a crossbow to shoot toxic arrows into their foes.

And these arrows consist of extremely sharp tips, long spikes and lethal toxins.

So, when a bacterium shoots such an arrow into another bacterium, it also shoots these toxins.

However, it is still not well understood how bacteria glue these toxins to the type 6 secretion system spike.

And how do bacteria protect themselves from the lethal activity of the toxin?

A new study tried to answer exactly these questions.

The known toxins of the type 6 secretion system nanoweapon

This study focused on the pathogen Escherichia coli. This bacterium defends itself with a crossbow and a special arrow. The spike of that arrow carries a so-called lipase toxin. This toxin dissolves the membrane of its prey to kill it.

But the researchers were curious about how this lipase toxin sticks to its spike. So, the researchers looked at the spike of the arrow and found that it has a little extension. And this extension seems to work like a patch to stick to the toxin.

Other bacteria have similar patches on their type 6 secretion system spikes. And in these bacteria, the patches are necessary for the toxin to stick to the spike.

The new study found that the toxin remains inactive when it sticks to the spike protein. Nicolas Flaugnatti, the author of the study, says, that: “This data was, in my opinion, one of the most exciting of this story”. It seems that the bacterium produces the spike protein and the toxin together. But at the same time, the bacterium protects itself from the toxin’s activity.

So, after the bacterium fired the spike into the prey bacterium, the toxin needs to fall off the spike to be active. For this, Nicolas considers this scenario: maybe the spike-toxin complex hijacks a protein from the prey. This could break apart the toxin-spike complex and activate the toxin.

What does the type 6 secretion system spike look like?

Next, the researchers wanted to understand how the spike inhibits the activity of the toxin. For this, they needed to know what the type 6 secretion system spike with the toxin looks like. To see the spike, they used a special form of microscopy.

And they found that the spike complex kind of looked like a jester hat. This could mean that the spike binds three toxins and delivers all three in one firing event.

This was very exciting for everyone involved in this study. Yet, it did not explain the toxin inhibition. So, Nicolas and his colleagues asked other labs with better microscopy techniques for help. Together, they visualised the smallest details of the spike, so that now they have a high-resolution structure of it.

A structure, which the whole field was waiting for.

While the structure for the spike was already known from other bacteria, it was the first time that someone “saw” the toxin. They found that the toxin has an elongated structure and that three toxins bind around one spike.

From this, the researchers understand how exactly this toxin binds to the type 6 secretion system spike.

Great stuff.

And they saw that the spike seems to shield the toxin. Like this, it cannot bind to the membrane and break it apart.

So, this is how the bacterium protects itself from the toxin. Otherwise, the toxin would dissolve the bacterium’s own membrane.

Why do we need to know the structure of the type 6 secretion system spike?

Researchers already consider the type 6 secretion system nanoweapon a promising tool to transport proteins. However, to actually use this delivery device, we need to understand exactly how the toxin sticks to the spike.

Other studies already tried to glue other toxins to the type 6 secretion system spike. However, so far, they only knew of one of these interaction patches. It seems that having just one of these patches is not enough for a toxin to stick to its spike.

Now, that we know more details about these patches, it would be possible to engineer proteins with the right patches to stick to the spike. One possible application would be to produce probiotic bacteria that fire arrows with particular toxins to kill pathogens. 

Another idea would be to block the patches between spike and toxin. For this, it is necessary to know the structure of the type 6 secretion system spike to design specific inhibitors. Then, the bacterium would shoot blank bullets instead of toxic arrows.

Inactivating this weapon could even prevent the colonization of undesirable bacteria.

Great science makes for a great story 

Researchers learn more and more about this fascinating killer machine. While my own time studying this nanoweapon is over, I still love to follow all the news around it. 

Now that we know the structure of a toxin-loaded spike, so many questions are answered.

Problems that I could not solve, finally make sense. 

I found inner peace.

The post Understanding the type 6 secretion system spike of a bacterial killer machine appeared first on Bacterialworld.
Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

Yes, bubbles!

No, bacteria don’t just produce bubbles and try to hit another microbe with them. They are more sneaky. Bacteria fill these bubbles with antibiotics. And antibiotics are toxic and kill microbes.

So, when these toxic bubbles hit other bacteria, they will suffer.

Let’s look at where these bubbles come from and why bacteria decide to fill them with antibiotics.

Bacteria and their membrane(s)

Bacteria come in one of two kinds. They can have one or two cell membranes.

If a bacterium has one cell membrane, it is called Gram-positive. If it has two cell membranes, an inner and an outer membrane, it belongs to the Gram-negative bacteria. 

The outer and inner membranes of Gram-negative bacteria are slightly different. Interestingly, the inner membrane of Gram-negative bacteria is the same as the cell membrane of Gram-positive bacteria. But in Gram-positive bacteria, that membrane has a lot of additional stuff to make it thicker.

Because Gram-negative bacteria have two membranes, their outer membranes can form “blebs”. These blebs, also called vesicles, eventually form round spheres – or bubbles – and detach from the membrane which is how they are released into the environment.

Bacteria and their outer membrane bubbles

As you can see, these bubbles are made from the outer membrane of Gram-negative bacteria. This is why they are called outer membrane vesicles. These are basically a double layer of lipids in the form of a sphere with stuff inside. 

Within these bubbles, bacteria pack anything that they want to get rid of. This can be cell junk and can come from cell machines that don’t work anymore. Bacteria can get rid of that stuff by throwing it out.

About Chromobacterium violaceum

One bacterium that produces these outer membrane vesicles is Chromobacterium violaceum. And this one has a special reason to produce bubbles: it uses them to kill other bacteria.

Chromobacterium violaceum produces the antibiotic violacein. Violacein is a purple molecule and turns Chromobacterium colonies into purple dots. 

Since violacein is an antibiotic, it kills other bacteria. However, this antibiotic only kills Gram-positive bacteria, those with only one cell membrane.

The problem with violacein is, that it is a very hydrophobic molecule. This means that it is insoluble in water. Hence, researchers were interested to find out how Chromobacterium transports violacein through water to other bacteria. 

Chromobacterium violaceum bacteria produce toxic bubbles

So, researchers had a look at Chromobacterium cells. They saw that these bacteria produce bubbles from their outer membrane. And they do indeed look like spikey bubbles as in the picture below.

The researchers then purified the vesicles and added them to Staphylococcus aureus, a Gram-positive bacterium. The vesicles killed Staphylococcus aureus, hence the researchers thought that the violacein would be inside these vesicles.

Then they grew a Chromobacterium mutant that did not produce any violacein. But this mutant still produced outer membrane vesicles. Surprisingly, the vesicles from this mutant did not kill Staphylococcus aureus. 

From this, the researchers concluded that Chromobacterium transports the violacein within the bubbles.

This meant that the researchers found new functions for outer membrane vesicles. Hence, bacteria use them

a) to solubilise a hydrophobic molecule

b) to transport a hydrophobic and toxic molecule towards other bacteria

c) as bacterial weapons

Now, this concept gives researchers interesting possibilities to apply outer membrane vesicles.

Maybe, one day we will find a way to fill these bubbles with therapeutic molecules and send them towards tumour cells or we just found a new way to deliver antimicrobial substances in general.

For sure, scientists will come up with some cool new ideas to use outer membrane vesicles in the clinic, but as always, that requires a lot more research ?

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Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

They might be crossbows and arrows, lethal sticks or chemical molecules. All these weapons are different means for bacteria to deliver toxins – or their bullets – into their prey.

But these toxic bullets are what finally kills the prey. And these molecules can act completely different within the prey cell.

So, here we want to look into what exactly bacterial toxins are and what they do once they reach the other cell.

What are bacterial toxins?

Here, we will focus on toxins that harm bacteria or other microbes. Bacteria also produce toxins that they deliver into human cells and yes, sometimes these have similar activities. However, we will not include these here.

Another note to consider: As we said, these toxins are meant to kill bacteria. Hence, the producing bacterium needs to be safe from the toxin as well. So, whenever a bacterium produces a toxin, it also produces a so-called immunity or anti-toxin. This is a protein that binds to the toxin and neutralizes it. Like this, the toxin is inactive and no danger to the producing cell.

So, what sort of compound is a toxin actually.

Most toxins are proteins with enzymatic activities. In general, enzymes catalyse biological reactions using two substrates and fuse them together or break them apart. 

However, enzymatic activities of toxins often break up components that are essential for life. And if this essential component is not present anymore, the cell cannot survive. So, like this, toxins are what ultimately kill prey cells.

Currently, researchers know of a few classes of bacterial toxins. Yet, they keep finding more and more.

Bacteria deliver different classes of toxins

Nucleases

DNA is “the molecule of life”. Hence, it makes perfect sense that destroying this essential molecule kills a prey bacterium. Indeed, the most potent toxins are nucleases that break up DNA inside a bacterium. If there is no DNA inside a bacterial cell, the cell cannot produce any proteins and enzymes to stay alive.

To make proteins out of DNA, another step is essential: the production of RNA out of DNA. RNA and DNA are both nucleic acids (which is why these toxins are called nucleases), but RNA is the transcript for the cell machinery to produce proteins. Hence, some nucleases do not break up DNA, but they specifically chew up the RNA in a bacterial cell.

The outcome is basically the same; the bacterium cannot produce any protein and will eventually die. So, nucleases destroy the roots of every living cell.

Bacteria deliver nuclease toxins to destroy the DNA or RNA of the prey and stop it from producing proteins.

Cell-envelope degrading toxins

The cell envelope is what keeps all the components within the bacterial cell together, gives a bacterium its shape and protects a cell from the surrounding. Just as your skin keeps your whole body together and protects it from the outside. This makes the bacterial cell envelope another easy target to destroy a bacterium.

Depending on whether a bacterium belongs to the Gram-positive or Gram-negative category, it has one or two layers of the cell envelope. Gram-positive bacteria usually have one thick and rigid cell wall, while Gram-negative bacteria have two cell membranes between, the-called periplasm. Within the periplasm is some kind of loose mesh that holds the inner and outer membrane together. 

Researchers found lots of toxins that can break up any of these layers. Some toxins can specifically chew up the thick and rigid cell walls of Gram-positive bacteria. Other toxins aim at one of the two membranes of Gram-negative bacteria or the mesh component in the periplasm.

In each case, the toxin has an enzymatic activity, that breaks up the molecule of which the layer is made.

So, some bacteria deliver toxins to chew up layers of the bacterial envelope. 

Pore-forming toxins

Pore-forming toxins actually do not have enzymatic activity. Instead, they have the unique ability to form holes in a bacterial cell envelope. When a bacterium has holes in its cell envelope, the cell content leaks to the outside. Also, the liquid from the environment can stream into the cell and eventually burst the prey cell. 

Thus, some toxins make holes in the bacterial cell envelope so that the bacterium loses its shape and protection.

Cell-function inhibitors

These kinds of toxins are the most versatile since many ways exist to inhibit the functioning of a cell. We will focus only on a few toxins here. But keep in mind that for some toxins, researchers still don’t completely understand how they work. 

Most of these toxins have one thing in common: They break up or inhibit an essential molecule within the bacterial cell. As such, a lack of this molecule stops the bacterium from functioning or growing. 

For example, to produce proteins, every cell needs ATP. This is the molecule in which cells store energy. Researchers just recently found one toxin that destroys ATP molecules within a prey cell. This makes it impossible for the prey to produce any more proteins. And we already know how his story ends.

Other toxins break down essential cofactors. Cofactors are vitamins, which every cell requires for example for cellular respiration. If a cell cannot perform cellular respiration, it does not produce ATP. And if a cell does not have any ATP? You know it ? !

Some bacteria deliver toxins to break up essential molecules in the prey and stop it from growing.

Bacteria deliver toxins for a good kill

You see the pattern here, right?

Whenever bacteria deliver toxins into prey bacteria, they want to hurt them real bad. This means, that a toxin generally targets any of the essential components of the prey bacterium to make sure there is no chance of survival. 

So, even though we talk a lot about the weapons that bacteria use to kill their prey, it is ultimately the toxins that kill!

The post The bacterial armoury appeared first on Bacterialworld.
Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

Especially for the killing process, bacteria have a full arsenal of killer weapons at their disposal.

They can start a chemical war, burn their foes, roll over them or punch holes into them with a bow and arrow.

But each of these decisions comes with a price; they cost energy and resources.

Especially activating and shooting killer bows and arrows is incredibly costly for a bacterium.

So, before bacteria decide to kill, they need to take their whole environment into account.

Here, we will look at when bacteria activate and engage their nanoweapon, the type 6 secretion system.

A bacterial weapon to kill when needed

Bacteria have this incredibly efficient killer T6SS weapon that looks like a crossbow with arrows. They shoot these arrows together with toxins into their foes to kill them and get rid of them.

However, you can probably imagine that bacteria can’t just fire these arrows randomly all the time. Producing the machine as well as the arrows costs a lot of energy. Hence, bacteria need to make sure they only produce and fire this weapon when it is required. Or that they gain something out the kill – like when they protect their hosts from intruders. So, they need to decide well.

Two recent studies (here and here) looked at four different bacterial species from the Vibrio genus. They focused on these bacteria because they all have very similar bacterial nanoweapons but seem to use them differently.

Also, some bacteria from the Vibrio genus can cause diseases in us or marine animals. Hence, research focuses on these bacteria to better understand them.

Two proteins control the killer weapon

Generally, bacteria from the Vibrio genus use two proteins to control when to produce their T6SS weapons. We will call these two controllers protein X and protein Y.

Interestingly, in these species, protein Y also controls the motility of the bacterial cell. So, this protein regulates how active the bacterial rotor, the flagellum, is. If it’s rotating very fast, the bacterium can swim forward. If the rotor is quiet, the bacterium stands still.

On the other hand, protein X controls an activity called competence. Bacterial competence means that the bacterium produces a special machine on the cell surface. This machine picks up free DNA from the environment. Once a bacterium takes up external DNA, it can stitch the new DNA into its own DNA. Now, this bacterium has new “powers” depending on what the new DNA is for.

These two studies looked at the links between the two controller proteins and the killing machine. And what they found, helps us better understand the bacterial lifestyle and decision-making.

Bacteria decide to kill and steal DNA

One main focus of research is on the bacterium Vibrio cholerae. This pathogen lives on seafood and can cause extremely dangerous diarrhoea in us. This is why it is important for researchers to better understand how this bacterium lives and survives in water and in the environment.

In Vibrio cholerae, both proteins X and Y control the T6SS weapon. As soon as Vibrio cholerae killed a neighbouring bacterium, protein X activates the competence machine. Now, the bacterium can take up the DNA of the dead bacterium and integrate it into its own.

With this behaviour, Vibrio cholerae not only kills competitors but also evolves. After getting rid of a foe, it gets new DNA and thus new superpowers for challenging conditions.

However, sometimes Vibrio cholerae realises it does not have a chance against its competitor. In this case, protein Y activates motility and the bacterium can swim away and escape the predator.

Bacteria decide: should I kill or should I go?

Then, both studies looked at whether the control of the T6SS weapon works similarly in other Vibrio species. They looked at these bacterial species:

• Vibrio parahaemolyticus, which causes diarrhoea and lives in seafood
• Vibrio fischeri, a squid symbiont
• Vibrio alginolyticus, another seafood-poisoning cause

All of these bacteria live in marine environments and can live in fish or seafood. Since they all cause some form of diarrhoea, researchers try to understand these bacteria better to inhibit the diarrhoea-causing mechanisms.

Both Vibrio parahaemolyticus and Vibrio alginolyticus have two T6SS weapons while Vibrio fischeri only has one. Interestingly, they are all active at different temperatures, so bacteria already control their killing activity depending on how warm or cold it is.

Also, proteins X and Y control each T6SS weapon completely differently in each bacterium. There is no pattern. None.

So, why would very similar proteins have completely different impacts on the T6SS weapons in different bacteria?

And does this mean bacteria decide differently about whether to kill or not?

There is currently no clear answer to this. So, my guess would be that it depends on the killing power of the T6SS weapon. Some T6SS weapons can kill other bacteria. Then it makes sense to activate the competence machinery at the same time. Like this, the attacker bacterium can also take up the dead bacterium’s DNA. 

However, other T6SS weapons are supposed to kill higher species, like fungi or amoeba. But a bacterium could not use the DNA of such a species. In this situation, the competence machinery is not needed. Rather, motility would be more appropriate to escape this dangerous situation.

It remains mysterious around this T6SS killer machine and how bacteria decide to kill. Or not.

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Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world