Chapter 15: Microbial Mechanisms of Pathogenicity

Exam 3

What is the 1st line of defense?

The 1st line of defense prevents pathogen entry into the body. This includes skin, mucous membranes, tears, saliva, stomach acid, and normal microbiota, which block microorganisms from entering tissues.

What is the 2nd line of defense?

The 2nd line of defense limits the spread of pathogens after entry. This includes phagocytic white blood cells, inflammation, fever, and antimicrobial substances that work to contain infection.

What is the 3rd line of defense?

The 3rd line of defense identifies, locates, and removes specific pathogens. This involves the adaptive immune response, including B lymphocytes, T lymphocytes, and antibodies.

How do microbial pathogenic traits relate to host defenses?

Microbial pathogenic traits are mechanisms that help microbes overcome host defenses. These traits help pathogens enter the body, evade immune responses, obtain nutrients, spread, and exit to infect another host.

What is the portal of entry?

The portal of entry is the specific route used by a pathogen to enter the host. Common portals include the mucous membranes, skin, and parenteral route (punctures, cuts, bites, injections).

What is penetration or evasion of host defenses?

This is the ability of a pathogen to penetrate tissues and avoid destruction by the immune system. Examples include capsules that resist phagocytosis, enzymes that break tissues, and antigenic variation.

What is meant by damage to the host?

Damage to the host occurs when pathogens destroy cells directly, release toxins, use host nutrients, or trigger harmful inflammation, leading to disease symptoms.

What is the portal of exit?

The portal of exit is the route a pathogen uses to leave the host and spread to another host. Examples include the respiratory tract, gastrointestinal tract, genitourinary tract, blood, and skin lesions.

Why must pathogens enter the host?

Pathogens must enter through a portal of entry to gain access to tissues and begin infection.

Why must pathogens attach to the host?

Pathogens must attach using structures such as adhesins, pili, fimbriae, or surface proteins so they are not removed by mucus flow, urine, saliva, or other defenses.

Why do pathogens need to hide from the immune system?

Hiding helps pathogens avoid phagocytosis, antibodies, and immune cell recognition, allowing them to survive and multiply.

Why do pathogens need to spread and gain access to host resources?

Pathogens spread to obtain nutrients, reproduce, and invade tissues, which can result in tissue damage and disease.

Why must pathogens exit the host?

Pathogens must leave through a portal of exit to be transmitted to a new host and continue the infection cycle.

What is the overall sequence of microbial pathogenicity?

1. Portal of entry 2. Penetration or evasion of host defenses 3. Damage to the host 4. Portal of exit

How do microbes enter a host through a portal of entry?

Through specific routes that allow access into the body, including mucous membranes (respiratory, gastrointestinal, genitourinary, conjunctiva), skin, and the parenteral route.

How would microbes gain access to the body?

By entering through: • respiratory tract (inhalation of droplets/dust) • gastrointestinal tract (food, water, hands) • genitourinary tract (sexual contact) • conjunctiva • skin breaks / wounds • needles, bites, cuts, surgery (parenteral route)

Are all microbes equally pathogenic?

No. Microbes differ in pathogenicity and virulence, so some are more likely to cause disease than others.

How does the number of invading microbes affect disease development?

A higher number of microbes increases the likelihood of infection because host defenses are more likely to be overwhelmed.

How does the type of microorganism affect the likelihood of disease?

Different microorganisms have different levels of virulence, so some require only a few cells while others require a much larger number.

What is ID50?

The infectious dose required to infect 50% of a test population.

What is LD50?

The lethal dose required to kill 50% of a test population.

What does a lower ID50 or LD50 indicate?

Greater virulence because fewer organisms are needed to cause infection or death.

Does the number of invading microbes required to cause disease vary by microorganism?

Yes. The infectious dose depends on the organism and its virulence factors.

Why is adherence important for microbial infection?

Microbes must attach to host cells to colonize, resist removal, and establish infection.

What are adhesins?

Surface molecules (ligands), usually glycoproteins or lipoproteins, that allow microbes to attach to host cells.

What do adhesins bind to on host cells?

Host receptors, usually sugars such as mannose.

Which microbial structures are involved in adherence?

• fimbriae • pili • capsules • flagella

How does microbial cooperation contribute to adherence?

Different microbes work together to attach and colonize surfaces, increasing survival and infection.

What is an example of microbial cooperation in disease?

Streptococcus mutans and Actinomyces working together in dental plaque formation and cavities.

What is a biofilm?

A community of microorganisms attached to a surface and embedded in a protective extracellular matrix.

Why are biofilms important in infection?

They protect microbes from immune defenses and increase resistance to antibiotics.

What are examples of bacterial adherence to host tissues?

• E. coli attaching to urinary tract cells • Streptococcus mutans attaching to teeth • Neisseria gonorrhoeae using pili to attach.

What host defenses limit microbial adherence?

• mucus trapping microbes • cilia moving microbes out • tears and saliva washing surfaces • urine flow flushing microbes • skin shedding • normal microbiota competing for attachment sites • IgA antibodies.

What is a portal of exit?

The route by which a pathogen leaves the host.

What are the major portals of exit for microbes?

• respiratory tract • gastrointestinal tract • genitourinary tract • skin and wounds • blood.

How are portals of exit related to portals of entry?

They are often the same routes used for entry into the body.

What are capsules, and what are they made of?

Capsules are part of the glycocalyx and are typically made of polysaccharides that surround the bacterial cell.

Why is a capsule considered a virulence factor?

A capsule helps bacteria avoid host defenses, especially phagocytosis, allowing the pathogen to survive and establish infection.

What host line of defense and mechanism is avoided by the presence of a capsule?

The capsule helps bacteria evade the second line of defense, specifically phagocytosis by white blood cells.

What are examples of encapsulated bacterial pathogens?

Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, Bacillus anthracis, and Yersinia pestis.

Would the identification of an encapsulated bacterium be a presumptive indication of a pathogenic bacterium?

Not always, because some nonpathogenic bacteria can also produce capsules, but it is often a strong indication of increased virulence.

How does mycolic acid found in acid-fast bacteria contribute to virulence?

Mycolic acid creates a waxy cell wall that helps bacteria resist phagocytosis and survive inside host cells, especially in Mycobacterium tuberculosis.

How does Opa protein found in Neisseria gonorrhoeae contribute to virulence?

Opa proteins promote attachment to host cells and help the bacterium invade epithelial cells, allowing it to avoid some immune defenses.

How does M protein found in Streptococcus pyogenes contribute to virulence?

M protein helps the bacterium resist phagocytosis by interfering with immune recognition and attachment by phagocytes.

What do mycolic acid, Opa protein, and M protein all help bacteria do?

They help bacteria avoid host defenses, especially phagocytosis and immune recognition.

What is the difference between endoenzymes and exoenzymes?

Endoenzymes function inside the bacterial cell, while exoenzymes are secreted outside the cell and act on host tissues.

Which enzymes are most likely to contribute to pathogenicity in the early stages of infection?

Exoenzymes, because they are secreted to help bacteria invade tissues and spread through the host.

What do coagulases do, and how do they contribute to virulence?

Coagulases clot fibrinogen into fibrin, forming a clot around bacteria that helps protect them from phagocytosis.

What do kinases such as streptokinase and staphylokinase do?

They break down fibrin clots, allowing bacteria to spread through tissues.

What does hyaluronidase do, and how does it contribute to virulence?

Hyaluronidase breaks down hyaluronic acid in connective tissue, helping bacteria spread through tissues.

What does collagenase do, and how does it contribute to virulence?

Collagenase breaks down collagen, allowing bacteria to invade muscles and connective tissues.

What do IgA proteases do?

IgA proteases destroy IgA antibodies, helping bacteria evade mucosal immune defenses.

What is antigenic variation?

Antigenic variation is when pathogens change their surface antigens to avoid recognition by the immune system.

What part of the host immune system does antigenic variation counteract?

It counteracts the adaptive immune response, especially antibody recognition.

Why does antigenic variation increase virulence?

It allows bacteria to escape antibodies and immune memory, leading to continued infection.

What are invasins?

Invasins are bacterial surface proteins that allow bacteria to enter host cells by affecting the cytoskeleton.

Which bacteria are capable of penetrating the host cell cytoskeleton using invasins?

Salmonella and E. coli.

What is membrane ruffling?

Membrane ruffling is the rearrangement of the host cell membrane and cytoskeleton that helps engulf bacteria into the cell.

If a bacterium penetrates the host cell cytoskeleton, where is the bacterium located?

It is located inside the host cell.

What part of the host immune system cannot work when bacteria are inside host cells? Why?

Phagocytosis and many circulating immune defenses cannot effectively work because the bacteria are hidden inside host cells.

How do these mechanisms allow bacteria to get in and stay in the host?

They help bacteria avoid immune defenses, invade tissues, enter host cells, and resist destruction, allowing infection to persist.

How do bacteria gain access to nutrients they need?

By obtaining nutrients from the host, especially iron, and by damaging host cells to release nutrients.

What are siderophores?

Siderophores are iron-binding molecules secreted by bacteria that remove iron from host proteins and transport it back into the bacterial cell.

Why are siderophores important for bacterial pathogens?

They allow pathogens to obtain iron, which is essential for growth and metabolism.

How do bacteria cause direct damage to host cells?

They attach to host cells, use host nutrients, multiply, and may cause host cell rupture and tissue damage.

What can happen after host cell rupture from direct damage?

Pathogens are released and can spread to surrounding tissues and infect other cells.

Why are toxins considered a virulence factor?

Because they damage host cells and tissues and contribute directly to disease.

What is toxigenicity?

Toxigenicity is the ability of a microorganism to produce toxins.

How do exotoxins act in relation to the bacterium?

They act outside of the bacterium, so the bacteria do not need to be present for damage to occur.

What are exotoxins made of?

They are proteins and may have enzymatic activity.

Why can exotoxins be long lasting even in low amounts?

Because they are water soluble and are easily transported throughout the body.

Are exotoxins target specific?

Yes, they are specific for particular tissues or organ systems.

What does “neuro-” indicate in an exotoxin name?

It indicates the toxin affects nervous tissue.

What does “entero-” indicate in an exotoxin name?

It indicates the toxin affects the gastrointestinal tract.

What does “cardio-” indicate in an exotoxin name?

It indicates the toxin affects the heart.

What does “leuko-” indicate in an exotoxin name?

It indicates the toxin affects white blood cells.

How else can exotoxins be named?

Other exotoxins are named for the specific bacterium that produces them, such as botulinum toxin and Vibrio enterotoxin.

What are the three major categories of exotoxins?

A-B toxins, membrane-disrupting toxins, and superantigens.

What does the A component of an A-B toxin stand for?

A stands for active and is the portion that disrupts host cell function.

What does the B component of an A-B toxin stand for?

B stands for binding and is the portion that binds to the host cell.

How do A-B toxins damage host cells?

The B portion binds to the host cell, allowing the A portion to enter and disrupt cell function.

How do membrane-disrupting toxins damage host cells?

They damage the plasma membrane, causing cell lysis.

How do superantigens damage the host?

They overstimulate the immune system by causing excessive cytokine release.

Where are endotoxins found?

In the outer membrane of Gram-negative bacteria as part of LPS, specifically Lipid A.

When are endotoxins released?

When the cell wall is compromised or when the bacterial cell dies.

Are endotoxins water soluble, and do they have protein or enzymatic properties?

No, they are not water soluble and do not have protein or enzymatic properties.

What symptoms are associated with endotoxins?

Chills, fever, weakness, aches, shock, and possibly death.

How does Lipid A affect the host immune response?

It stimulates macrophages to release cytokines, which trigger a series of events in the body.

What can Lipid A cause?

Lipid A can cause septic shock and endotoxic shock.

How can Lipid A cause septic shock and endotoxic shock?

By increasing vascular permeability and decreasing blood pressure.

How do plasmids contribute to pathogenicity?

Plasmids may carry genes for virulence factors, and plasmids can be passed to other bacteria.

How can latent virally infected cells contribute to pathogenicity?

They may contain virulence factor genes from a previously virally infected bacterial cell.

What can happen when the virus enters the lytic cycle to exit the host?

The viral genome may pick up virulence genes from the host.

How can virulence genes be passed to other bacteria by viruses?

Viruses can transfer these virulence genes to other bacteria, acting like nature’s vectors.

What does “nature’s vectors” mean?

It means viruses carry virulence genes from one bacterial cell to another.

Clostridium botulinum

• Type: A-B
  

• Name: Neurotoxin
  

• Target: Nervous system / neuromuscular junction
  

• Effect: Stops nerve impulse transmission → results in flaccid paralysis
  

• Disease: Botulism

Clostridium tetani

• Type: A-B
  

• Name: Neurotoxin
  

• Target: Muscle relaxation pathway
  

• Effect: Blocks nerve impulses to muscle relaxation pathway → results in uncontrollable muscle contractions (spastic paralysis)
  

• Disease: Tetanus

Corynebacterium diphtheriae

• Type: A-B
  

• Name: Cytotoxin
  

• Target: Nerve, heart, and kidney cells
  

• Effect: Inhibits protein synthesis → results in cell damage/death
  

• Disease: Diphtheria

Staphylococcus aureus

• Type: A-B
  

• Name: Exfoliative toxin / cytotoxin
  

• Target: Skin cells
  

• Effect: Causes separation of skin layers → results in skin sloughing
  

• Disease: Scalded skin syndrome

Vibrio cholerae

• Type: A-B
  

• Name: Enterotoxin
  

• Target: Intestinal cells
  

• Effect: Secretion of fluids and electrolytes → results in diarrhea
  

• Disease: Cholera