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Costs and benefits of adaptations

So far, we have seen that pathogens are microbes with adaptations that allow them to bypass immune barriers. We have also discussed the idea that pathogens cause disease by damaging host cells. In this lesson, we put both these ideas together: a pathogen has adaptations that enable it to infect a host, and cause disease by damaging host cells. Think about this, if a microbe can infect a host permanently without causing a disease, is it a pathogen or is it a commensal?

As we have seen, pathogenicity is a host-microbe interactions and pathogenic bacteria need adaptations to bypass immune defenses to gain access to nutrients, which often leads to host cell damage and disease. In other words, the very tools that are used to bypass host barriers are often the ones that cause disease. This relates to the idea that a microbe can be commensal in one part of the body and pathogenic in another. For example, many species who live in the intestines are perfectly harmless, and even beneficial. But if during a surgery, they get transferred from the gut into other tissues, e.g., the blood, they may start growing there, causing severe disease.

LESSON 4.3 WORKBOOKHow do bacteria adapt to become pathogens? -The adaptation auction

As we have learned before, pathogens have evolved tools that allow them to bypass host defenses. These tools are called adaptations, and include structures, growth rate, and toxic compounds. Pathogens need to be able to invade the host, and stay camouflaged to avoid the immune system if they are to persist in the host. They also must find nutrients to sustain their growth. Today, we will focus on how specific adaptations can cause host damage, and can be used to gain access to nutrients.

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DEFINITIONS OF TERMS

Colonization — permanent inhabiting of the host.

Inflammation — a complex response of immune system,

leading to heat, redness, pain, and swelling aimed to clear infec-

tions.

For a complete list of defined terms, see the Glossary.

1. Some commensal bacteria can adapt and become pathogens.

.a True

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In this lesson, we will build the perfect pathogen for a specific ecological niche in the human body using what we have learned so far in the course. We will do this by weighing the costs and benefits of individual adaptations. Every adaptation we add, will aid the pathogen in surviving in the human body but will also cost the pathogen resources to be produced and maintained.

Gram-positive cell walls

Gram-positive bacteria have a thick cell wall composed mainly of the murein polymer corset that surrounds the bacteria like a chain-link fence. Gram-positive bacteria survive well in environments with high-salt concentrations, such as the skin. These bacteria also have LTA (lipoteichoic acids) on their surface, which can stimulate the immune system, and elicit powerful host cell responses. These responses may cause tissue damage allowing

the bacteria to spread to other locations or may lead to the removal of the infection. In addition, the LTA molecules allow the bacteria to adhere to host cells, aiding colonization of the host.

Gram-negative cell walls

Gram-negative bacteria have a cell wall that contains one-two thin layers of murein, and an additional outer membrane. The membranes are separated by a perisplasmic space that contains enzymes that can inactivate antibiotics. Gram-negative bacteria also contain LPS on their surface, an endotoxin that causes severe inflammation. The presence of LPS can elicit a strong immune response that results in host cell damage. At its most severe, LPS plays a role in septic shock, a potentially fatal state of overinflammation resulting from bacterial infections. As with LTA, the immune response might also use LPS to 'see' and clear the infection.

Figure 1: Gram positive bacteria have a thick cell wall allowing them to survive in high salt environments.

Figure 2: The main components of Gram-negative bacterial cell wall.

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2. Which of the following best describes the role of acid-fast cell walls?

.a enables the bacteria to survive in harsh environments or when nutrients are depleted

.b grow in conditions without oxygen

.c spread quickly from host to host

.d contains large amounts of waxes laced with murein, sugars, and lipids, so they can hide from immune cells and resist its chemical barriers

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Acid-fast cell walls

The cell walls of acid fast bacteria have external layers with waxy properties. These outer layers contain fatty acids, sugars, and lipids helping them to hide from immune cells, and resist the chemical barriers of the immune system. In addition, antibiotics have a hard time getting through the waxes, making these bacteria less susceptible to treatment. But this waxy layer does slows down the flow of nutrients into the cells, which is why acid-fast bacteria like Mycobacterium tuberculosis (the agent that causes TB) — grow very slowly.

Slow replication rates

Bacteria that replicate slowly require fewer nutrients over a given period of time, and pathogens with low replication rates often persist for long periods causing chronic infections. The slow rate of growth also makes these bacteria harder to treat with antibiotics because most antibiotics only work on actively dividing bacteria. Sometimes the immune system will block off these bacteria into structures called granulomas, as we saw with TB, allowing the bacteria survive without damaging the host. Low replication rates also have their downside, however, as it means that bacteria cannot spread as quickly or as easily.

Fast replication rates

High replication rates allow bacteria to spread quickly from host to host, and from tissue to tissue. In contrast with slow growing bacteria, these pathogens are generally susceptible to antibiotics unless they have acquired antibiotic-resistant genes. One downside of high replication rates is that these bacteria require lots of nutrients over a short period of time. Hence, these bacteria generally cause acute disease, which can even kill the host, depriving the bacteria of resources unless they find a new host quickly.

Adhesion pili

If bacteria have no way of attaching and sticking to host cells, they will probably be eliminated from a host pretty quickly. However, many bacteria have external hair-like structures, called pili, that allow them to attach to surfaces. Once bacteria bind to such surfaces, they can start reproducing, and further adhere to the surface and stick close to

Figure 3: Acid-fast bacteria, pink rods, visualized with a proper staining method.

Figure 4: Pili on a bacterial surface.

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3. During starvation, this adaptation allows a bacterium to condense the content of its cytoplasm into ____.

.a exotoxins

.b flagella

.c spores

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each other forming a biofilm. In fact, the dental plaque on your teeth, which you work so hard to control by brushing and flossing, is a biofilm! Cells in a biofilm form a community that works together to protect each other from the immune system. Biofilm infections are harder to treat with antibiotics. Some estimates suggest that biofilm formation plays a role in about 80% of all infections. Biofilm formation is a huge problem for medical devices such as catheters or implants that are inserted into a patient's body. If such devices get contaminated and colonized by bacteria, they will become an internal source of infection that can sometimes be deadly.

Flagella

Flagella make bacteria motile, so they can actively seek out new environments and nutrients. This may lead to spread of infection or colonization of a host if the bacteria travel to previously protected locations. For example, H. pylori uses its flagella to swim away from the stomach lumen (center), where the stomach juices have a low pH, towards the epithelium lining of the stomach, where the pH is closer to neutral. This is a crucial adaptation that H. pylori uses to colonize the harsh stomach environment.

Flagella can also play a direct role in disease through the H antigen, the major protein that builds the flagella. This protein can be recognized by the immune system, leading the clearance of the infection. To counteract this, some bacteria can switch between making different kinds of H antigen in order to hide from the immune system. Spores

Some Gram-positive bacteria can condense their genetic material and the contents of their cytoplasm into spores. This usually happens when nutrients are depleted, allowing the bacteria to survive starvation as well as other harsh environmental conditions such as extreme dryness. Bacillus anthracis is an example of a spore forming bacteria that causes Anthrax. Anthrax sores can wait for idea conditions to germinate for decades!

Figure 5: Biofilm of S. aureus cells (light grey cocci) on a catheter.

Figure 6: H. pylori using its flagella to swim towards more neutral pH.

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4. This adaptation allows bacteria to break down the matrix of surrounding cells to spread more rapidly into deeper tissues. It can cause direct and indirect damage.

.a exotoxins

.b conjugates

.c exoenzymes

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Capsule

Some bacteria have an external layer called a capsule, which is made of complex sugars, surrounding the cell wall. These sugars resemble the sugars on the surface of host cells thus helping the bacteria 'fool' the immune system into 'seeing' the bacteria as self-cells. The capsule can also help bacteria survive very dry environments, and attach to surfaces. Famous examples of capsulated pathogens include Strep. pneumoniae and Neisseria meningitidis.

Replicating extracellularly

Replicating outside cells allows bacteria to quickly migrate to new areas when nutrients become depleted. In addition, these bacteria are often able to survive and spread on inanimate objects. On the downside, bacteria replicating extracellularly are exposed to the immune system and inconsistent environments, and only have access to nutrients that exist outside of host cells.

Replicating intracellularly

Replicating within cells allows bacteria to take nutrients from the host and hide from (evade) immune cells. These bacteria spread by causing host cell lysis. One downside of replicating intracellularly is that the bacteria usually need a host cell to survive, making it more difficult to spread to new areas to access nutrients or to new hosts. Additionally, they may be dependent on the conditions that exist within a particular cell, making them less adaptable to changing environments than extracellular bacteria.

Exotoxins and Endotoxins

Exotoxins are proteins that are secreted into a bacteria's surroundings to aid survival, and to allow bacteria to spread into deeper tissues. Examples of exotoxins are the Shiga, tetanus, botulinum, and cholera toxins. Unlike exotoxins, endotoxins are part of the cell wall and are not secreted. Like exotoxins, they also elicit inflammation, allowing bacteria to spread into deeper tissues. A few examples include LPS in Gram-negative bacteria, and LTA in Gram-positive bacteria. Both exotoxins and endotoxins can cause direct and indirect damage to a host. Please refer to Lessons 4.1 and 4.2 for more information on their modes of action.

Figure 8: Chlamydia clusters of cells (see arrows) inside host cells.

Figure 7: Capsules (see white halos around the dark pink cells) are used as camouflage structures by bacteria to evade the immune system.

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DEFINITIONS OF TERMS

Extracellular matrix — a fine meshwork of proteins outside

cells in a tissue that holds them in place.

For a complete list of defined terms, see the Glossary.

5. Which statement accurately describes endotoxins?

.a it allows bacteria to share genes

.b part of the cell wall that can elicit inflammation and allow bacteria to spread into deeper tissues; can cause direct and indirect damage

.c proteins that are secreted into surroundings to aid survival and allow bacteria to spread into deeper tissues; can cause direct and indirect damage

.d break down the matrix of surrounding cells to spread more rapidly into deeper tissues; can cause direct and indirect damage

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Produces exoenzymes

Exoenzymes are enzymes released by bacteria to perform a number of tasks. Bacterial exoenzymes can be used to break down complex nutrients such as sugar polymers, breakdown host structures or cells to gain access to new locations, counteract the immune response, or wall themselves off from the immune cells. One of the most notorious exoenzyme producing bacteria is Staphylococcus aureus. It produces numerous exoenzymes that perform different functions such as clotting the fibrin in blood plasma to wall off the immune system; enzymes that break down the extracellular matrix surrounding cells to spread more rapidly into deeper tissues, and enzymes that can break down red blood cells, and even host DNA.

Figure 9: S. aureus cells (cocci in the middle) clotting blood proteins and covering themselves with the clots to hide from the immune system.

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Remember to identify your sources

Describe the advantages and disadvantages of being an intracellular pathogen.

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Eating food contaminated with a pathogenic strain of E. coli makes you sick. Your gut contain a very similar strain of E. coli —

why doesn't the version of E. coli in your gut make you sick?

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Provide an explanation for why the populations of E. coli living in our guts have not adapted to make us sick.

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TERMS

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TERM DEFINITION

Antigenic Foreign agents, such as pathogens, that have the ability to provoke a very specific response by the immune system.

Colonization Permanent inhabiting of the host.

Extracellular matrix A fine meshwork of proteins outside cells in a tissue that holds the cells in place.

Inflammation A complex response of the body, orchestrated by the immune system, that aims to protect the body from a foreign intruder.

Mycolic acids Fatty acids found in the cell walls of Mycobacterium sp.