So, when we take antibiotics because of a bacterial infection, billions of bacteria are suddenly attacked by antibiotics.

They struggle to repair damage, maintain their structures and continue essential functions just to stay alive.

This ultimately weakens or kills the cells.

And as you can imagine, this is pure stress for the bacteria.

One that we take advantage of.

This article series takes you on a journey through the microscopic war between bacteria and antibiotics. Across five articles, we will explore how antibiotics attack bacteria, how bacteria overcome them, become resistant and how evolution pushes bacteria to survive the antibiotic war.

In this first part of the series, we explore how different classes of antibiotics work, while focusing on the most commonly used antibiotics. Once you understand these mechanisms, you will better understand how and why bacteria fight back, evolve and develop resistance.

Antibiotics attacking bacterial cells by stopping cell division

Bacteria have a rigid cell wall made of peptidoglycan to maintain their shape and internal pressure and to protect them from the environment. Without the ability to build or repair the cell wall, bacteria become fragile and burst easily.

This vulnerability is precisely what antibiotics from the β-lactam family exploit. You have probably heard of penicillin, one of the most well-known members of this class. Other similar antibiotics are amoxicillin and cephalosporins.

How these antibiotics work is pretty simple but devastating to bacterial cells: they block the so-called penicillin-binding proteins. These enzymes sit in the cell wall where they are responsible for building and cross-linking it.

So, when a bacterium gets hit by a β-lactam antibiotic, it loses the ability to divide. Basically, every time it tries to divide, it will burst like a water balloon.

Antibiotics sabotaging bacteria’s genetic machinery

Every bacterial cell carries instructions for life in its DNA, the molecule that stores genetic information. Before dividing, bacteria copy their DNA and then share it with their daughter cells.

Bacteria also make RNA, the molecule that executes the instructions stored in DNA. RNA comes in different types with distinct roles, but it is fundamentally needed to make proteins from DNA.

Some antibiotics exploit this vulnerability by inhibiting one of the cell’s information-processing machineries. This fundamentally interferes with DNA or RNA synthesis. If a bacterium can’t produce DNA or RNA, it can’t divide or maintain its genetic integrity, leading to cell death.

The antibiotic class fluoroquinolones inhibits DNA production. For example, ciprofloxacin freezes the enzymes that help bacteria copy their DNA. When DNA replication stalls, bacteria cannot divide. They accumulate damage and eventually die.

In comparison, rifamycins inhibit RNA synthesis. These antibiotics bind to the RNA polymerase, the enzyme that produces RNA from DNA. They thereby block the first step in protein production.

It’s like cutting electricity to an entire factory; without RNA, the cell cannot produce proteins, halting metabolism and growth. This is highly stressful to bacteria and can quickly kill them.

Antibiotics blocking protein production: The ribosome hijackers

Other antibiotics directly inhibit the protein production step: To build proteins, bacteria produce a temporary working copy of those DNA instructions, the so-called messenger RNA or mRNA.

This molecule travels to the ribosome, which reads the mRNA and makes proteins from it. Since proteins are essential for metabolism, movement, growth and cell division, no cell can function without them.

Some antibiotics, like tetracycline, take advantage of this protein production vulnerability. By interfering with ribosomes, these antibiotics prevent them from producing proteins and eventually the bacterial cells from functioning.

Interestingly, not all protein-production inhibitors kill bacteria in the same way. Some antibiotics are bacteriostatic, which means they freeze growth without immediately killing the cell. The bacteria cannot make new proteins, so they can’t divide or repair themselves. Instead, the existing proteins remain active for a while, allowing the cell to survive in a weakened state.

Others, like aminoglycosides, are bactericidal. Instead of simply blocking ribosomes, they cause the ribosome to make mistakes and produce misfolded proteins. These faulty proteins build up inside the cell and damage essential structures, overwhelming the bacterium, so it eventually dies.

Antibiotics disrupting metabolic pathways

Lastly, some antibiotics target essential metabolic pathways that bacteria need to survive. For example, folate is an essential vitamin that all organisms need to grow and reproduce, and most bacteria have proteins to make their own folate. So, when antibiotics block these folate-producing proteins, the bacterium will eventually run out of folate and lose the ability to grow.

How different antibiotics kill bacteria

As we’ve seen in this post, antibiotics can impact bacteria in many different ways. But they all have the same goal: do the biggest damage possible. Antibiotics can damage a bacterium’s DNA, its protein production machinery, metabolic pathways or the cell envelope.

This damage is essentially stress for the bacterium: they must repair the damage or adapt their metabolisms to it. If they cannot cope with the damage or the stress, they’ll die. And remember, this was basically the antibiotic’s goal from the beginning.

But be aware: this stress can be both lethal and a driving force for bacterial evolution. As they learn to cope with the antibiotic and the stress, they become resistant. And in future articles, we will explore these bacterial learning processes and how they help make bacteria resistant to antibiotics.

The post How Antibiotics Kill: The Weapons We Use Against Bacteria appeared first on Bacterialworld.
Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

The complement system is the first line of immunity defence

As part of the innate immunity, the so-called complement system consists of several proteins. These get activated sequentially and function together to finally destroy any pathogen.

To recognise harmful bacteria, complement proteins have special receptors. These bind to specific proteins on the surface of the bacteria, so-called pathogen-associated molecular patterns, or PAMPs for short.

Imagine the bacterial PAMP as a key that perfectly fits into the groove of an immune receptor lock. The binding between these two proteins activates the immune system and triggers mechanisms that aim to clear out the pathogen.

The enzymatic lock & key hypothesis.

The immune system recognising different bacteria

Bacteria come in two main types: Gram-positive and Gram-negative bacteria. Depending on which type a bacterium is, it has different PAMPs. Luckily, your immune system has evolved to identify both of these structures.

Gram-positive bacteria are surrounded by a rigid layer, the so-called peptidoglycan cell wall. Within this layer of carbohydrates and proteins are the modified carbohydrates teichoic acid and lipoteichoic acid. These are the PAMPs, that your immune system recognises and binds to.

The Gram-positive bacterial cell surface. Created with BioRender.com.

On the other hand, Gram-negative bacteria contain an additional capsule layer on top of the peptidoglycan wall. This layer is made up of another type of carbohydrate, the lipopolysaccharide, which is the PAMP of Gram-negative bacteria. So, even though Gram-negative bacteria also contain a peptidoglycan cell wall, it is covered by the capsule and thus inaccessible to the immune system.

The Gram-negative bacterial cell surface. Created with BioRender.com.

How does the complement system work

Imagine a harmful bacterium managed to sneak into your body. To prevent any intruder from causing damage, the sensor proteins of the complement system are constantly patrolling the bloodstream, hunting for malicious beings that aim to harm the body.

As soon as a sensor protein recognises and binds to a bacterial PAMP with its lock, it alerts the complement system. The sensor protein begins to produce a key enzyme called C3 convertase.

A complement sensor protein binds to a bacterial PAMP. Created with BioRender.com.

Within your blood, there are lots of small complements called C3. And the main function of the C3 convertase is to break down this C3 into small C3a and large C3b fragments. This is the most important step in complement activation and from here everything else happens.

C3 convertase production and its subsequent action. Created with BioRender.com.

Now, the bloodstream is flooded with C3b fragments which bind to the bacterium’s surface. As more C3 proteins are broken down, more C3b large fragments are produced and more bind and coat the bacterium. This process is called opsonisation.

Illustration of opsonisation by C3b. Created with BioRender.com.

The immune system gets rid of bacterial intruders

The C3b-covered bacterium now acts as a location device for phagocytes. These arrive and bind to the C3b fragment very tightly. This keeps the bacterium locked and prevents it from moving around.

Now begins the process of phagocytosis, whereby arm-like structures extend around the bacterium, eventually engulfing, ingesting and destroying it. The infection is finally cleared.

Phagocytosis of a bacterial pathogen.

In some cases, however, phagocytes do not arrive fast enough to the site where the C3b-covered bacterium hangs around. In this case, other complement proteins, such as C5 and C6, begin to spontaneously assemble around C3b and form the so-called membrane attack complex (Figure 6). This complex punctures a hole into the cell surface, which looks like a gunshot wound, causing the bacterium’s innards to spill out and dissolve.

Formation of the membrane attack complex via the self-assembly of complements. Created with BioRender.com.

How does the complement system differentiate between commensal and pathogenic bacteria?

You are probably aware that in your body also live many friendly bacteria, the so-called commensal ones. And you do not want to get rid of these helpful bacteria. Hence, the immune and complement systems have adapted several strategies to keep your friendly bacteria and focus their killing power on harmful intruders.

For example, commensal bacteria reside only in certain areas of your body like the gastrointestinal tract. They do not float around in the blood. Your immune system is aware of this. Hence, the complement system in the gastrointestinal tract is modified and does not attack these commensal bacteria. Instead, their recognition skills focus on harmful intruders.

Also, commensal bacteria contain additional molecules on their surfaces to hide their PAMPs from the complement system. This prevents the complement system from getting activated.

The complement system as the first immune fighters

As you’ve seen, the complement system works tirelessly, day and night, patrolling your bloodstream to ensure that no harmful bacterium gets too comfortable inside. With its sensor proteins, it identifies these pathogens and activates the immune army to clear out any infection.

Hence, the complement system is the crucial first line of defence of our immune system. By recognizing and targeting harmful bacteria and sparing beneficial commensal bacteria, it ensures that your body remains healthy and free from infection.

The post How your immune system battles harmful bacteria every day appeared first on Bacterialworld.
Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

Yes, also plants have a lot of delicious and nutritious food for bacteria.

And just as bacteria can be good or bad for us and our bodies, bacteria can be good or bad for plants. Some bacteria help plants grow while other bacteria harm plants. These are the so-called plant-pathogenic bacteria.

These plant-pathogenic bacteria can infect plant leaves, roots or fruit. You might have seen weird spots on plant leaves or on crops or opened a spoiled piece of fruit.

You can imagine that some bacteria developed some really smart ways to live in or on our bodies. Similarly, some bacteria found methods to live and thrive in and on plants and protect themselves from their immune attacks.

This means that plant-pathogenic bacteria learned to recognise that they landed on plants, enter them and cause diseases to use the plant’s nutrients. But before any of that happens, let’s have a look at where plant-pathogenic bacteria come from.

How do bacteria land on plants?

Bacteria are everywhere around us. They live on almost any surface – be it alive or not – but also in the air we breathe.

And some bacteria even live in clouds or on sand dust. Hence, through rain or sand storms, these bacteria are transported to new areas and arrive on new soils.

Other bacteria use animals or little bugs to get transported. When the transporting animal comes into contact with plants, it can brush off the hitchhiking bacteria.

When a bacterium comes into contact with a plant leaf, it uses special adhesion proteins to link to the plant surface. These proteins bind specifically to proteins on the plant.

After this happened, some plant-pathogenic bacteria like Xanthomonas form biofilms. These work like slimy houses that surround the bacteria and protect them from weather, sunshine or drought.

So, for now, the bacteria are safe inside their biofilm houses. In there, they can grow and reproduce and get ready for their big attacks.

How do bacteria know when they arrived on plants?

Before launching an attack to infect a plant, the bacterium needs to know that it actually IS on a plant. And for that, some bacteria learned to speak the language of plants.

Yes, also plants send out words to tell themselves and other plants what is going. These words are chemical molecules. And some bacteria developed special antennae or receptors on their surfaces to bind these molecules.

This means bacteria can listen to and understand what plants say. And this tells bacteria that they actually arrived on a plant.

However, one bacterium cannot launch a plant-destroying attack by itself. It needs to know that it has support from its sibling bacteria. And for that, bacteria also talk to each other.

So, bacteria also send out words in the form of chemicals. And they listen to their own words so that they know that they are not alone. Now, they can start their attacks to make their way into the plant.

But plants also know how to protect themselves: Plants can interfere with bacterial chatter. For that, plants produce chemicals that bind these bacterial words. Now, bacteria cannot talk to each other anymore and think they are on their own, so an attack is probably not worth it.

And then there is the plant microbiome that protects the plant from bad things like harmful bacteria. However, plant-pathogenic bacteria learned to fight off the plant protection shields.

How do plant-pathogenic bacteria make their way into plants?

Even though plants have special protection mechanisms to keep bacteria from entering, plant-pathogenic bacteria found clever ways around them. Just as pathogenic bacteria can fight off our immune defences and end up making us sick.

As one way to protect against pathogenic bacteria, plants cover their surfaces with a waxy layer. This is a physical barrier for bacteria while it also prevents the water inside the plant from evaporating.

However, the bacterium Pseudomonas syringae developed its very own bacterial superpower to circumvent this barrier: This plant pathogen produces ice crystals even above freezing temperatures.

These ice crystals harm the waxy layer, cut open the plant envelope and cause the so-called frost injury. With such an injury, the plant loses water and the bacteria can enter the plant through the open wound.

Other plant pathogens move specifically towards the stomata on the surface of plants. These are the gates that let gases like carbon dioxide enter the plant. And interestingly, these bacteria produce certain chemicals that keep these gates open so that the bacteria can enter the plant.

Once the bacteria are inside the plant, they can start their attacks. For this, they use special bacterial weapons that transport toxins into the plant. These toxins then disrupt the plant from functioning properly and make them sick.

So, just as pathogenic bacteria learned to bind to and enter our human bodies, plant-pathogenic bacteria developed mechanisms to specifically enter plant organs. Hence, one goal of researchers is to understand how bacteria achieve this. The idea is to create plants that are resistant to plant-pathogenic bacteria.

The post How plant-pathogenic bacteria understand plant language and make them sick appeared first on Bacterialworld.
Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

However, some bacteria found a way to become invisible in front of the immune cell army. They put on an invisibility cloak so that they can sneak into the human body without being seen. This invisibility cloak is a so-called bacterial capsule. And pathogenic bacteria use capsules to trick the immune system to infect our bodies.

Here, we will explore what bacterial capsules are and how bacteria use them to overcome our immune systems.

About bacteria with capsules

Bacteria that produce capsules are generally pathogens. These are bacteria that can infect us, cause disease and make us sick. And bacterial pathogens use capsules for the infection process. Without capsules, pathogenic bacteria would be eaten and killed by our immune cells.

Bacteria with capsules are for example Klebsiella pneumoniae, Mycobacterium tuberculosis, Haemophilus influenzae, pathogenic and uro-pathogenic Escherichia coli, Neisseria meningitidis and Porphyromonas gingivalis.

Many people carry Klebsiella pneumoniae in their gastrointestinal tract or nose without having any symptoms. However, in some people, this bacterium can enter the blood circulation and cause infections like pneumonia, sepsis, urinary tract infections, bacteremia or meningitis.

The pathogen Mycobacterium tuberculosis causes the devastating disease tuberculosis with almost 1.4 million deaths every year. Haemophilus influenzae infections lead to sinusitis and uro-pathogenic Escherichia coli causes urinary tract infection. Another awful pathogen is Neisseria meningitidis. This bacterium infects the membrane around our brain and leads to the disease meningitis. Lastly, Porphyromonas gingivalis is an oral pathogen that infects and destroys the tissue around our teeth. You might know this disease as periodontitis.

This list of pathogenic bacteria might sound a bit frightening. But it is to highlight the one feature they all have in common: These bacteria use their capsules to enter our bodies and cause these diseases.

So, let’s have a look at what this capsule actually is.

What are bacterial capsules

The bacterial capsule is a thick layer of a sugar-water mix that surrounds the bacterial cell.

The capsule layer consists of long chains of sugar molecules that are attached to the bacterial cell surface. These sugar molecules have different lengths, lots of branches and different attachments. The sugar chains absorb water molecules so that a gooey slime develops. Researchers can even see this under the microscope.

Interestingly, different bacteria can produce chemically identical capsules. But the same bacteria can also produce different capsules. In this case, bacteria add little attachments to the outer tip of their sugar branches. Now, this bacterium “looks” completely different from the outside.

Generally, antibodies bind to these sugars, which is why we call these sugars antigens. However, when bacteria change their sugar tips, they also change their antigens. Hence, another antibody is needed to recognise this new antigen – even though it might still be the same sugar. In this case, we call the bacterium with the new sugar antigen a serotype.

For example, researchers found 80 different antigens and thus serotypes in Escherichia coli based on their capsule sugars. And for Streptococcus pneumoniae, they even identified 93 serotypes.

Now, you might ask yourself what is the function of capsules in bacteria?

Bacterial capsules are invisibility cloaks

A bacterial capsule works like an invisibility cloak. As soon as a bacterium enters the dark halls of our human bodies, it puts on the cloak. Now it won’t be seen by the immune guardians. Like this, bacterial pathogens follow the model of “the best defence for a pathogen is a good defence”.

The players of our immune system recognise and bind to specific molecules on the surface of bacteria. This activates the immune system and attracts more phagocytes. These immune cells eat intruding pathogens and destroy them. Like this, our immune army is always ready to fight the bad guys.

However, the bacterial capsule hides these surface molecules that our immune system usually recognises. Like this, our immune players cannot bind these sugar-coated pathogens. This keeps the immune army deactivated. Now, bacteria can escape the immune system, sneak into our bodies and cause infections.

Our immune system can also fight intruding bacteria by producing antimicrobials. Yet, the sugar capsule of some bacteria can absorb these small molecules and make them useless. Hence, the bacterial capsule acts as a protective layer against immune attacks.

Neisseria meningitidis even has a “capsule-switch”. Once activated, it can cover itself with another sugar layer that looks completely different from the outside. The immune players need to learn again to recognise this new layer, which takes time. Hence, with this “hyper-encapsulation”, Neisseria meningitidis can escape the immune system again.

Overcoming bacterial capsules

Because bacterial capsules are at the outer surface of a bacterium, researchers want to use these components as targets for vaccines. However, since bacteria can change their capsular components, these targets are not very reliable. So, researchers are working on developing vaccines that recognise different serotypes.

For example, a vaccine that recognised different antigens of the capsule in Klebsiella pneumoniae was developed and reached clinical trials. However, the high costs of such an efficient vaccine made this project difficult.

Another approach is to better understand how pathogenic bacteria regulate their “capsule-switch”. If we can prevent bacteria from putting on another cloak, we can help our immune system do its job and kill intruding bacteria. Hence, researchers are looking for ways to achieve this.

Bacterial invisibility cloaks – another way for bacteria to survive

You might now think how nasty bacteria are for using such a capsule to escape our immune system and infect us. However, for bacteria, this is another survival mechanism. If they do not put on their invisibility cloak, the immune system will eat and kill them. So, some bacteria developed this mechanism to overcome their foes.

And I think it is a pretty smart way to survive.

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

Many of our organs have a slimy mucus which is supposed to stop bacteria from entering the human body. But some bacteria developed mechanisms to swim through this gel-like mucus faster than others.

And these bacteria are usually the ones that make us super sick.

Meet the bacterial race swimmer Campylobacter jejuni

The pathogenic bacterium Campylobacter jejuni for example causes food-poisoning and watery diarrhoea. And this pathogen can swim through gel-like slimes, like the mucus in our bodies. Other bacteria are slowed down by this slime, but not Campylobacter jejuni. It even swims faster when it hits slime!

Why is that?

Well, that is exactly what researchers were trying to find out.

Two flagella for one movement

Campylobacter jejuni looks pretty cool. It has a helical shape and one flagellum on each side of the cell. Flagella are like fine hair that grow out of the bacterium. 

Closer to the membrane of the bacterium, the flagellum becomes a so-called hook. This hook is connected to a little motor inside the bacterium. And this motor rotates, which then rotates the hook and thus the flagellum. Now, the flagellum works as helical propeller and this movement pushes the bacterium forward so that it swims.

Since Campylobacteria jejuni has two flagella of different length, researchers were curious about how this bacterium would move. Two motors would constantly push the bacterium in the opposite direction. Plus, they saw previously that this bacterium can swim faster than other bacteria in slime. But they had no idea how these two flagella would work together. 

Wrapped in flagella

To see the flagella under the microscope, they changed them slightly. Like this, they could stain the flagella and see them as yellow fluorescent tails under the microscope.

They saw that in watery liquids, half of the bacteria had both their flagella spread to both sides and they were swimming slowly. This you can see on the left side in this video. The other half had one flagellum rotating as a tail at the back and the other flagellum was wrapped around the bacterial cell.

In gels (in the video on the right) almost all the bacteria (>95%) had one of their flagella wrapped around their cells. Plus, these cells swam faster and more directed. Mind-blowing!

Two motors are better than one

So, the researchers wanted to know why Campylobacter jejuni wraps the flagellum at the front around its cell and how that helps the bacterium to swim faster. They created two mutants of this bacterium: One bacterium did not have a front-flagellum and the other did not have a tail-flagellum. 

And they looked at how these mutants swam in comparison to the bacterium that has two flagella. In the video below, you can see the bacterium with two flagella on the left, the bacterium with the tail-flagellum in the middle and the bacterium with the front-flagellum on the right.

And as you can see, the bacteria in the middle had their tail-flagellum propelling. This pushes the bacterium forward so that it swims. Bacteria with the front-flagellum still swam. And the researchers confirmed that this front-flagellum is still rotating. It works as if it drills the bacterium forward.

So, when bacteria have two flagella, it has double the power; and the pushing and drilling together makes this bacterium super fast.

Changing direction

Next, the group was interested to see how Campylobacter jejuni changes its swimming direction. Luckily, they managed to film one bacteria at the moment when it decided to swim towards the other side.

In this video, you can see that first the front-flagellum changes the direction of its rotation. Like this, it is getting unwrapped from the bacterium.

Then, the tail-flagellum also changes its direction of rotation and the bacterium halts its movement. This looks as if the bacterium tumbles trying to get to the new direction.

Next, the former tail-flagellum wraps around the bacterium and becomes the front-flagellum.

And the former front-flagellum becomes the tail-flagellum and rotates to push the bacterium towards the opposite direction.

Two flagella to get to the perfect location

Researchers already knew that other bacteria also wrap their flagella around their cells. But often this happens in trapped places so that the bacterium tries to protect its flagellum. However, Campylobacter jejuni with its two flagella developed some efficient mechanisms to infect the human body. 

• Its helical shape helps the bacterium to drill through slimy mucus

• A rotating front-flagellum pulls the bacterium actively forward helping with the drilling movement of the bacterium

• The tail-flagellum rotates to propel the bacterium forward

• By quickly changing its swimming direction, Campylobacter jejuni can escape from confined spaces or maybe even immune cells in the human body

I’m always amazed by what bacteria come up with to escape dangerous situations…

So, now that we better understand how this pathogen moves in our bodies, we better understand how it infects us. This knowledge will now help to fight this pathogen. Let’s hope that it will help us get rid of such nasty food-poisoning-causing bacteria. 

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

What does stress mean for bacteria?

For humans, stress can come from juggling work, family, exercise, entertainment, and whatever else life throws at us (like a world-wide pandemic!). Bacteria also can get stressed; however, they experience and react to stress differently than us. Salmonella enterica is a great example of a bacterium that has many ways to deal with different stress in its life.

You’ve probably heard of Salmonella enterica because it can cause food poisoning. While there are many different strains of this bacterium, I’ll only be discussing the ones that lead to food poisoning and I’ll refer to it as Salmonella in this post. Unfortunately, there are about 1.3 million food poisoning infections a year from Salmonella.

About the pathogen Salmonella

Salmonella naturally lives in the guts of chickens, so handling chickens or eating undercooked or raw eggs could put you at risk of getting sick. That’s why you’re not supposed to eat raw cookie dough (even though it’s so good). Good hand hygiene and cooking meat and foods thoroughly reduce the risk of getting sick.

However, if by any chance a Salmonella bacterium makes its way into our bodies, it travels to the small intestine. Here, it will start to reproduce, leading to diarrhea and stomach cramps associated with food poisoning.

But if you think about it, it has to be challenging for Salmonella to live in all those different environments, from chicken guts to the inside of eggs to human stomachs and intestines. Each of these environments has a different temperature, pH, and different nutrients. And the change of just one of these conditions is “stress” for the bacterium. That’s where having the ability to deal with stress comes in handy for Salmonella.

Let’s look at each of these challenges for Salmonella bacteria and how they deal with stress.

How Salmonella handles temperature stress

Salmonella likes to grow in the warm environments of chicken and human guts.

And like humans, bacteria also react to being too cold. This can happen when Salmonella lives in a chicken egg and a chicken lays this egg. All of a sudden, Salmonella lives in outside temperatures. But instead of bundling up with some hot cocoa and a blanket, Salmonella makes proteins to protect itself.

When bacteria are too cold, the genetic information (DNA, RNA) stiffens and adopts a shape that’s hard for the cell to use. This is why the cell makes special proteins that protect the shape of DNA at colder temperatures.

Thus, the cell ‘blankets’ its genetic information to protect it and use it properly.

How Salmonella copes with acid stress

After coping with changing temperatures, Salmonella continues its journey to the human intestine. We consume Salmonella bacteria through contaminated food (like that raw cookie dough). Then they make their way down to the human stomach.

But our stomachs are very acidic. This is to help us break down food and kill pathogens. In acidic environments, proteins start to misfold and get destroyed, making them useless to the cell.

However, Salmonella and other pathogens know how to cope with this acidic attack. They produce so-called chaperones. These are special proteins that protect other proteins from misfolding. This keeps all other proteins active and thus the cell alive.

How Salmonella saves energy when food is limited

Now that Salmonella has survived the highly acidic stomach, it enters the intestines where it can find food and grow. Lots of bacteria live in our guts and all compete for the same amount of food.

For cells to grow, they need energy that comes from food. When food sources are limited, Salmonella cells will conserve energy by ‘turning off’ proteins that consume energy.

But why not just get rid of that protein if the cell does not need it anymore? The problem is, making proteins takes energy. If the cell needs the protein it just trashed in the future, the cell must invest more energy into making that protein again. By turning the protein off, the protein is not destroyed and can be used again later when conditions are better.

It is similar to changing from a green light to a red light at a traffic light. The red light halts cars from moving at specific times but does not destroy the car. Once traffic conditions favor that direction, the traffic light turns green and the cars can respond quickly and move through the intersection.

Similarly, Salmonella turns off its proteins in such a way that it can later remove the modification and restore the activity of the protein. Like this, Salmonella can respond quickly and turn on the protein when food becomes available. Once more food becomes available, Salmonella settles into the gut by eating, growing, and reproducing.

Unfortunately, as Salmonella gets comfortable in its new home, we become uncomfortable with fever, stomach aches, and diarrhoea. Now that sounds stressful!

Salmonella knows how to deal with stress

All these mechanisms of stress management allow Salmonella to thrive in a wide variety of environments. From chickens to humans, the road to pathogenesis is wrought with stressful situations. And lucky for Salmonella, it knows just how to deal with each of these situations of stress.

The ability to respond to stressful situations is common to bacteria, and each bacterium possesses its own set of proteins and pathways to handle stress and even aid in bacterial virulence.

So just like us, bacteria have to handle a lot of stress in their lives. But the more we learn about how pathogens like Salmonella deal with stress, the better we can fight them!

Take away messages from this week’s article

• Bacteria encounter many stresses in the environment
• They have various pathways to respond to different types of stress
• The ability to deal with varied environments and stress allows pathogens like Salmonella greater virulence and resilience

The post How does Salmonella deal with stress – a bacterial journey through the human body appeared first on Bacterialworld.
Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

This includes bacteria and human cells.

Why is that?

Because iron has essential functions in the metabolism of every living cell.

The problem is, that free iron is actually toxic.

So, each organism binds iron to a special vehicle.

And bacteria were smart enough and developed strategies to steal those vehicles from other organisms.

Want to find out how and why?

Read on.

The iron in our blood

In the human body, we have many different iron-carrying vehicles. Most of the iron in our body is stored in a special molecule called haem. Haem has a ring structure with the iron (Fe) bound in the middle

It looks more or less like in this picture.

Haem is part of a protein called haemoglobin. And haemoglobin lives in the membranes of each of our red blood cells.

The iron inside the haem inside the haemoglobin is the one that binds oxygen and carries it to all our cells.

Interestingly, when haem is bound to oxygen, it turns red. And because the haem is red, our blood is red. Without the oxygen, the haem complex is blue-red.

Bacteria stealing iron

So, our body stores most of the iron within these haem molecules. And many pathogenic bacteria developed strategies to survive within the body by stealing our haem and thus our iron.

To do this, they produce special transporters that sit in the membrane of the bacterium. This transporter looks like a barrel, like the blue one in the figure below. This barrel tightly binds haem and transports it through the membrane into the bacterium.

After bacteria imported the haem, they degrade the haem molecule to set the iron free and use the iron in their metabolism.

3 ways to steal our iron

A new study just found that my beloved bacterium of interest, Pseudomonas aeruginosa, actually contains three of these transporters. And all of these import iron into the cell. In this study, the researchers tried to understand why this bacterium would need three of these haem systems. Interestingly, they all seemed to have the same function – to find and import haem and thus iron.

The first thing they saw was that the bacterium produces any of these transporters only when it lives in a surrounding where there is little iron available. If a bacterium finds lots of iron, it takes it up easily without the need of these specialised transporters that cost a lot of energy.

Next, the researchers grew the bacteria with either no haem, a little haem or lots of it, while always keeping the iron low. Now they wanted to test under which conditions the bacteria would produce any of these three transporters.

When the cells grew with no or only a little haem, the bacteria produced one of the three systems, the so called Phu system. By producing this system even in the absence of haem, the bacteria prepare themselves for when haem comes along. Then they can immediately take it up and use it.

However, the Phu system did not work very efficiently when the bacteria grew with lots of haem. In this case, the bacteria produced the other two systems. These are the Hxu and the Has systems.

Why so many?

The Hxu and the Has systems are special transporter systems. And these are very similar to those that we discussed in the article “Bring in the iron”.

They contain the same barrel that you can see above. But the transporters are also involved in information sensing and messaging. This means that they not only take up the haem. These transporters also tell the bacterium that there is haem on the outside.

Like this, the bacterium knows that it is inside a host, as the human body. Because nowhere else would a bacterium find haem and especially in this amount.

Now that the bacterium knows that it is inside a host, it can produce all the heavy machinery to invade the host or make it sick.

Bacteria are always ready to find iron

But why does the bacterium need two of these haem transporting systems? Likely, as a safety net in case, one of them fails.

The researchers indeed found that the two systems can replace each other if one of them was missing. So with this, the bacterium makes sure that in any case the haem will be taken up and the iron used.

Now, the next step for the researchers will be to try to find drugs that can inhibit any of these transporters. This would cut off the messaging process and the bacterium would not know that it is currently inside a host. Then, it would not activate its heavy machinery to make us sick.

In all, this study told us a lot about how bacteria learn about their surrounding and showed us a new alternative to fighting these nasty bugs!

Take away from this week:

• Bacteria learn about the presence of haem in their surroundings to know they found a host
• Bacteria can use our haem to extract iron for their metabolic processes
• These transporters represent promising targets for anti-microbial drugs

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

During my last dentist sessions, I realised I barely know anything about the microbes that call my mouth their home. Those microbes and bacteria that live between my teeth and eat the same food that I eat.

Unfortunately, some of these bacteria can also cause a nasty disease that you might know as caries. And caries can lead to tooth decay and, eventually, cavities. Something, we all want to avoid.

However, as you will see below, it is not the bacteria that MAKE the holes themselves and cause caries. Rather, they fasten the process which you can prevent with good mouth hygiene.

So, let’s have a look at the microbes that live in your mouth and between your teeth and what they do there. We will then explore how some bacteria cause caries and cavities and why brushing your teeth is so important.

What your teeth are made of

Because the teeth in your mouth have to chew and shred all your food, they are made of very strong material. It’s actually the strongest material in your whole body.

This is why your body makes sure to keep your teeth healthy and strong. For example, the upper layer of your teeth – the so-called enamel – is made of pretty resilient calcium complexes. And this white and shiny layer constantly renews and mineralises on top of your enamel all the time.

Yet, at an acidic pH, the demineralisation process starts and removes calcium from your teeth. And when too much calcium leaves your teeth, the protective layer is broken. This is when holes form and thus caries and tooth decay.

So, you want to avoid getting the pH acidic in your mouth for too long. And this you can do by choosing the food you eat.

For example, acidic fruit like apples, oranges, and lemons can make the pH in your mouth acidic. Another problem can be sugary food. The microbes in your mouth can break apart the sugars in the food by microbial fermentation. From the sugars, they produce acids, which means the pH in your mouth becomes acidic.

However, your mouth doesn’t just let the pH drop easily. The saliva on top of your teeth means to buffer the pH in your mouth. Like this, it tries to keep the pH always at a constant level to prevent the demineralisation process.

About the bacteria living in your mouth

But the saliva in your mouth has another very important function. It keeps the teeth healthy and free from pathogenic bacteria. Some components of the saliva actively kill those bacteria that cause caries or prevent them from sticking to your teeth. Plus, saliva is constantly flowing through your mouth, which washes off most bacteria.

But we also have bacteria in our mouths that help us and even prevent diseases.

Some bacteria save you from caries

Some of the friendly microbes in our mouths live here and actually help us. These so-called commensal bacteria have special components – known as adhesins.

The adhesins bind to the proteins in the saliva, so that the bacteria can attach to the saliva and thus to the tooth. Here, they form a biofilm, which is a so-called plaque. This bacterial biofilm you can feel on your teeth in the morning just after waking up.

Within these biofilms, the friendly bacteria protect us from harmful pathogenic bacteria. For example, they actively kill intruding pathogens and produce toxins to keep them out of your mouth.

Plus, those commensal bacteria protect you from caries since they inhibit the demineralisation process of the enamel. For this, they produce special components that neutralise the pH and support the mineralisation process.

Other bacteria in your mouth can be nasty

And then we have pathogenic bacteria that are the sneaky ones and that can cause caries and tooth decay.

These bacteria have similar adhesins to bind to saliva and stick to your teeth. However, some of these bacteria can also bind to commensal bacteria, like the pathogen Streptococcus mutans. This one likes to stick to Candida albicans which is a member of our commensal mouth microbiota.

Other pathogenic bacteria can specifically bind to sugar molecules or use them as building blocks to increase the biofilm on your teeth. Like this, they create mixed biofilms of different bacteria.

And within this bacterial biofilm, bacterial wars are breaking out! The commensal bacteria fight the intruders to protect us. The invaders try to get rid of the friendly bacteria to make themselves a new home.

And unfortunately, pathogens have strong weapons. They can produce strong acids from sugars which make our mouths very acidic. And our friendly bacteria don’t like such an acidic environment as they have a hard time handling it. So, this acidic environment eventually kills the commensal bacteria so that the pathogens have the dental biofilm just for themselves.

Now, we call this biofilm cariogenic and this is the onset of tooth decay.

How some bacteria cause caries on your teeth

Within such a cariogenic biofilm, the pathogenic bacteria keep the pH acidic. This prevents the commensal bacteria from growing. But as we have seen above, acidity triggers the demineralisation process of the tooth enamel. And this eventually leads to holes or cavities in the tooth.

So, it is NOT the bacteria themselves that “eat” the tooth and cause caries! Caries comes from the acidic environment that these bacteria create.

Just as a bacterial biofilm protects the commensal bacteria from the surrounding, this cariogenic biofilm protects the pathogenic bacteria. They also just want to survive (but please not in our mouth!).

The cariogenic biofilm also keeps the pH acidic so that sugar molecules can better diffuse into the biofilm and the bacteria have enough food. This provides the pathogens with more sugar so that they can keep making acids. Unfortunately, the saliva and its protecting components cannot enter the biofilm.

Help your friendly bacteria protect you from caries

Basically, caries disease is a shift of our mouth microbiota from commensal bacteria to pathogenic bacteria. With more pathogenic bacteria on your tooth, the pH becomes more and more acidic around that area of the cariogenic biofilm. Hence, this triggers the demineralisation process in that area of the tooth, which can result in those nasty cavities everyone is so afraid of.

Now, that we better understand how bacteria cause caries and tooth decay, maybe it is easier to refrain from those sugary foods after hours. And if you can’t help it, make sure to brush your teeth to get rid of the sugar leftovers. This will prevent those nasty pathogens from settling down in your mouth and causing disease.

The post How bacteria cause caries on your teeth appeared first on Bacterialworld.
Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

However, to get into a human body, a bacterium needs to have certain mechanisms to stick to it and then to enter it.

Plus, the intruding bacteria need to overcome the defence mechanisms of the host itself. These defences can be our friendly bacteria that fight pathogenic bacteria or the immune system that sends off fighters. Also, our own microbiome works like a block against incoming new microbes.

And yet, some pathogenic bacteria developed some clever ways to stick to a host and infect it. Here, we will look at the different steps of how bacteria attach to a host and infect it.

Bacteria stick to a host

For a bacterium to infect a host cell, it first need to understand that it is actually close to one. For this, bacteria have so-called pili, which look like thin hairs sticking out of them.

These pili have special little patches at their ends. And when such a patch finds the right cell type, it can stick to it. Like this, certain bacteria can only stick to a specific host cells.

For example, the uropathogenic bacterium Escherichia coli can infect our bladders. This means that this bacterium has special patches at its pilus that specifically stick to cells in our urogenital tract.

Now, that the bacterium knows that it is close to a host cell, it shortens the pilus. This movement pulls the bacterium close to the cell itself.

The next step for the bacterium is to connect tightly to the host cell.

Bacteria connect to a host

To attach tightly to a host, pathogenic bacteria have little hooks called adhesins. These proteins can bind to specific components on the surface of the host cell.

So, after a bacterium pulled itself close to a cell, the adhesin binds to the cell more tightly. Also, not every bacterium has the right adhesin to binds to every host cell. Again, for this binding mechanism to work, they need specific adhesins for specific cells.

From this tight binding, the bacterium can easily enter the host cell. Once inside, it fires off its weapons like the T3SS or the T6SS. In the end, these weapons are what make the cell sick.

How a host fights off invading bacteria

Obviously, our body doesn’t want to get sick. Hence, it will not allow bacteria to easily invade us. This is why we have many different strategies to protect us from foreign microbes, toxic molecules or anything that could be harmful for us.

Here, we will look at a few mechanisms that our body uses to get rid of pathogenic bacteria.

Washing bacteria off

To avoid that bacteria come and attach to our cells, our body uses shear stress. This means that there is a constant flow of either air or blood to wash off all bacteria from the cells, so they don’t get (too) attached.

For example, in our nose we have little hairs which move with every inhale and exhale. These moving hairs are trying to wipe off incoming bacteria.

And don’t forget our very own microbiota. The good bacteria on our body also help us fight off incoming bad bacteria.

Fighting off bacteria

Our body developed a whole army that is trained to recognise and fight foreign microbes and bacteria. This is the immune system that consists of many different players that work together in incredibly complex mechanisms with the goal to protect us.

And some of these players are specifically trained to fight off incoming pathogenic bacteria.

For example, macrophages swim around our body always on the lookout for invading bacteria. There is this amazing video in which a macrophage chases a single bacterium and guess who wins?

However, many pathogenic bacteria found ways to escape these host immune cells. They have so-called flagella which they use to swim away from the immune cell.

How bacteria get too attached to a host

Here, we had a quick glimpse into the life of a pathogenic bacteria and how they infect a host. By better understanding how bacteria connect to hosts, we can develop more practical treatments to inhibit this mechanism. This would eventually keep bacteria from sticking to host cells and infecting them. In general, that would keep us free of disease and infections.

If you want to learn more about any of these steps here, please leave a comment in the boxes below. We will explore those topics in upcoming blog stories. We are looking forward to your ideas!

The post How bacteria get (too) attached appeared first on Bacterialworld.
Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world

For many, we know that certain bacteria can cause disease but exactly how they are able to infect their targets often remains a mystery.

One such system, responsible for promoting bacterial infection, is known as the type III secretion system (T3SS). This system looks and acts like a tiny biological needle!

The T3SS is part of a larger collection of secretion systems. Bacteria use secretion systems to move compounds around, to fight against other bacteria or to infect their hosts. The T3SS does that last job, it is used to infect higher organisms like humans or plant cells

The T3SS is a microscopic needle-like structure. It sticks out from the surface of the bacteria by around 50 nanometres (so very small!). The needle doesn’t just hang around all the time though. It is a moving system which can extend or retract as necessary.

The rest of the needle structure is buried within the cell membrane, which is like a bacteria’s skin.

The T3SS body is made of several different sized rings. Like the needle, the rest of the secretion system also moves and changes a lot. The entire system has lots of regulation where bacteria can turn their systems on or off.

The end of the needle, the translocon, can “pierce” the target host cells. These target host cells are usually from higher organisms such as plants and animals (including us humans).

By piercing the target cell, a stable link between the host and the bacterium has now formed.

The bacteria deliver effector proteins into their target. These effector proteins:

• Give rise to characteristic disease symptoms
• Minimise any immune response
• Establish bacterial infection

I guess you could say they get stuff done!

The bacteria physically pump these effector proteins using energy. This process is powered by a tiny biological motor. This motor is called an ATPase, a structure which produces energy. This ATPase motor is located right at the bottom of the system, and spins rapidly just like a tiny biological wind turbine.

The effector proteins are brought to the base of the secretion system. Effector proteins are drawn up the through the T3SS rings, out through the needle and into the target host cell.

The T3SS requires a lot of precious energy and resources to assemble and operate. Bacteria with better control over the system, can allocate resources more efficiently and only when necessary. This is an evolutionary advantage; they have a higher chance of survival and growth.

Depending on the bacterial species, full infection of a target can be achieved in just a few minutes or hours when using the type III secretion system.

Not all bacteria have this system but those which do, will often use it as their primary method for establishing infection.

An example of a bacterial species which does make use of the T3SS for infection is Pseudomonas aeruginosa. This is a common bacterium picked up in hospitals. It can become aggressively resistant to antibiotics and costs a lot of money for health care providers around the globe.

Researchers (like me) are trying to understand this system in more detail so that we can better arm ourselves against the fight against these bugs and against antibiotic resistance.

Perhaps we will hear more about this intricate and complex system in the near future. It is fast becoming a possible target for antibiotic drug design. Also, perhaps I’ll find out enough about these type III secretion systems to be able to fill a thesis with data and crown myself Dr. Danny Ward.

I’m specifically trying to understand type III secretion system regulation. A tiny molecule known as CdG (or cyclic-di-GMP in full) can bind to the T3SS and change a bacterium’s ability to infect. We don’t know how or why this works. I’m on a mission to find out more about this!

Why is this important, I hear you cry?

Not only will it expand our knowledge of the natural world, which you never know where that might lead, but it will also build a better foundation for developing control agents to stop bacteria with T3SS.

If we can spray a solution which will get the CdG to do all the hard work for us and stop the bacteria infecting, then we will have hit the jackpot!

I still have 2 more years still to go with the PhD, so time will tell as to exactly what I find!

Take away from this week’s article

• Some bacteria use tiny biological needles known as type III secretion systems (T3SS)
  to infect their target hosts
• These needle-like structures deliver effector proteins in to target cells which
  promote infection
• This system is driven by an ATPase which acts like a small, yet powerful biological
  motor.

The post Tiny Biological Needles: How Some Bacteria Are Able to Infect Their Targets appeared first on Bacterialworld.
Bacterialworld - A blog about bacteria: from scientific studies to vivid stories about the fascinating bacterial world