Clinical Microbiology HW#6

Microbiology Animation: Virulence Factors: Exotoxins

1. An exotoxin that has the ability to kill or damage host cells is referred to as a(n)

Cytotoxin

2. Which domain of the A-B toxin binds to cell surface receptors on the host cell?

B domain

3. How are superantigens different from other types of exotoxins?

Superantigens cause an overstimulation of the host immune system.

4. A person who attended a picnic early in the day develops a very high fever and is unresponsive by the evening. This person most likely has been exposed to a(n)

Superantigen

5. A patient who has been hospitalized with uncontrolled muscle spasms has probably been infected with bacteria that secrete a(n)

Neurotoxin

Microbiology Animation: Virulence Factors: Penetrating Host Tissues

1. Certain traits that allow pathogens to create infection and cause disease are termed

Virulence factors

2. Which of the following enzymes breaks down the "glue" that holds cells together?

Hyaluronidase

3. Which of the following virulence factors would be found in Staphylococcus aureus?

Staphylokinase

4. How do fibrinolysins enhance a pathogen's virulence?

They break down fibrin proteins that are involved in clot formation, allowing the cells to penetrate deep into damaged skin.

A Perfect Storm: Overcrowding, Poor Sanitation, and Vibrio cholera

In January 2010, a devastating earthquake struck Haiti about 15 miles west of the capital city of Port-au-Prince. The earthquake killed over 200,000 people and displaced over 1 million from their homes. Many of these people had nowhere to go other than displacement camps and shantytowns, where the sanitary conditions were less than ideal. It was not only private homes that were destroyed; hospitals, communication networks, land and air transport, and other important infrastructure were damaged.

In October 2010, a cholera epidemic was reported in the Artibonite Department (Haitian departments are analogous to states). This was the first cholera epidemic in Haiti in over a century. Within 10 weeks, cholera had spread to all Haitian departments. By the end of the epidemic, more than 470,000 cases had been reported, and more than 6500 people were dead.

Both during and after the epidemic, epidemiologists, doctors, and scientists were working to determine the source of the outbreak and its transmission patterns, identify the causative strains, and care for the infected.

1. The ability of Vibrio cholerae to cause disease depends on a number of factors. Which of the following are requirements for causing disease within a host?

Evasion of host defenses ; adherence to host tissues; gaining access to the host via a portal of entry

Gaining entry to the host is just part of the story. The number of organisms that enter the host is significant; enough bacteria must survive in order to establish the infection and cause disease. One measure of virulence is the ID₅₀ value. It is important to note that this value is determined experimentally and can vary for each pathogen under different conditions.

2. Some studies have indicated that the ID₅₀ for Vibrio cholerae can be as high as 10⁸ organisms. Which of the following most likely explains the requirement for this relatively high ID₅₀?

To establish infection, V. cholerae must survive the host immune response and the acidic environment of the stomach.

**The acidic environment of the stomach is extremely harsh on V. cholerae, and the microbe doesn’t possess particular virulence factors to help it combat this environment. Therefore, the high infective dose is needed to ensure that enough bacteria make it through the acidic environment and into the intestine, where the pH is much higher than that of the stomach. Once in the intestine, V. cholerae is able to begin to establish infection.

One of the virulence factors responsible for disease caused by V. cholerae is cholera toxin. This is an exotoxin produced by V. cholerae under specific environmental conditions found in the intestine.

3. Which of the following are properties of exotoxins?

Exotoxins target specific cellular structures or molecules.

Very small amounts of exotoxin can be lethal.

Exotoxins are protein molecules.

**Cholera toxin attaches to G proteins within host cells. This results in a disruption of signaling pathways in the host cell and, ultimately, in an electrolyte imbalance within the intestine. Water rushes out of cells and into the lumen of the intestine, causing the profuse, watery diarrhea that is associated with cholera.

4. Cholera toxin is an A-B toxin; A-B toxins exert their effects after entering host cells. Label the following figure to indicate the sequence of events leading to the activity of A-B toxins such as cholera toxin.

From top to bottom:

Cholera toxin A subunit

Cholera toxin B subunit

B subunit mediates binding to host cell via interaction with specific cell receptor

A-B toxin enters host cell via endocytosis

A and B subunits separate

B subunit leaves the cell

A subunit alters host cell function

5. The physical symptoms of cholera present only after a specific series of events has taken place. What is the most likely sequence of events in the pathogenesis of V. cholerae?

From left to right:

V. cholerae is ingested via contaminated water.

V. cholerae survives passage through the stomach and enters the intestine.

V. cholerae attaches via pili.

V. cholerae produces cholera toxin.

The host intestinal cells are destroyed, resulting in a profuse, watery diarrhea.

V. cholerae exits the host via the feces.

**You might reasonably think that elimination from the body in feces would not confer an advantage for the bacteria. However, this is quite advantageous for V. cholerae because it enables the pathogen to go on to infect another host. V. cholerae can also survive as an environmental organism, so it will be able to survive even if it is not immediately introduced into another host.

6. Although cholera can be treated with antibiotics, data suggest that antibiotic treatment alone is NOT the most effective therapy. Which of the following statements describes the most likely reason for supplementing antibiotic therapy?

Antibiotic therapy addresses only the growth of V. cholerae; it doesn’t address the extreme dehydration suffered by a person infected with V. cholerae.

**Antibiotics (particularly doxycycline) are commonly included in the treatment of cholera. However, rehydration therapy is considered more essential in the effective treatment of the disease. Rehydration therapy will replace the lost fluids and electrolytes that were lost with the watery diarrhea. This diarrhea is so profuse that patients can lose up to 20 liters of fluid a day! This extreme loss of fluid and electrolytes often has severe consequences, such as shock and death. However, with prompt rehydration treatment, patients can fully recover, even in areas of the world where the disease is endemic.

7. Disease research and epidemiology bring together many different facets to help us better understand disease pathology and spread. Which of the following statements are true?

The interactions that occur between a microbe and host influence the evolution of both.

Bacterial exotoxins can be altered to create toxoids, which can be used to produce protective immunity in a host.

Some pathogens are able to cause disease within a host without penetrating the body.

Chapter 15 Reading Questions

1. In mice, the LD₅₀ for staphylococcal enterotoxin is 1350 ng/kg, and the LD₅₀ for Shiga toxin is 250 ng/kg. Which of the following statements is true?

Shiga toxin is more lethal than staphylococcal enterotoxin.

2. Which of the following statements about lysogenic conversion is true?

Exotoxin production by bacteria is frequently the result of a lysogenic infection.

Chapter 15

1. The ability of some microbes, such as Trypanosoma or Giardia to alter their surface molecules and evade destruction by the hosts antibodies is called

Antigenic variation

2. Antibiotics can lead to septic shock if used to treat

Gram-negative bacterial infections

3. Which organism in the table most easily causes an infection?

Bacterium ID50 E. coli O157:H7 20 Legionella pneumophila 1 Shigella 10 Treponema pallidum 57

Legionella pneumophila

4. Many pathogens use the same portal for entry and exit from the body.

TRUE

5. In A-B exotoxins, the A component binds to the host cell receptor so that the B component can enter the cell.

FALSE

6. Biofilms provide pathogens with an adhesion mechanism and aid in resistance to antimicrobial agents.

TRUE

Microbiology Animation: Phagocytosis: Mechanism

1. What does the plasma membrane of a phagocyte attach to on a microorganism?

Glycoproteins

2. The process by which a phagocyte moves toward a chemical signal at the site of an infection is called

Chemotaxis

3. Which of the following phagocytic processes occurs last in the sequence?

Exocytosis

4. What is the role of opsonins?

They create "handles" that make it easier for the pseudopods of phagocytes to attach to the microbe invader.

5. What is a phagolysosome?

The structure that results from the fusion of a phagosome and a lysosome.

Microbiology Animation: Inflammation: Steps

1. What direct effect do histamines and leukotrienes have on capillaries?

They allow capillary walls to open and become leaky.

2. Diapedesis is

the migration of phagocytes through blood vessels to the site of tissue damage.

3. Why is vasodilation important to tissue repair?

It allows for an increased delivery of oxygen, nutrients, and phagocytes to the site of damage.

4. Pus is comprised of

dead phagocytes.

5. Which of the following can release histamines?

Cells from damaged tissues and the complement pathway

Chapter 16 Reading Questions

1. Activation of C3 results in __________.

All of these:

enhancement of phagocytosis via opsonization

release of histamine and other pro-inflammatory chemicals

formation of a membrane attack complex (MAC), which causes cytolysis of bacteria

2. Which of the following statements about innate immunity is true?

Innate immunity is present at birth.

Chapter 16

1. TLRs attach to all of the following EXCEPT

AMPs

2. A child falls and suffers a deep cut on her leg. The cut went through her skin and she is bleeding. Which of the following defense mechanisms will participate in eliminating contaminating microbes?

phagocytosis in the inflammatory response

3. Which of the following is an effect of opsonization?

increased adherence of phagocytes to microorganisms

4. Neutrophils with defective lysosomes are unable to

produce toxic oxygen products.

5. Several inherited deficiencies in the complement system occur in humans. Which of the following would be the MOST severe?

deficiency of C3