Bacterial Pathogenesis MCB 103/PMB 103: MIDTERM 2 | answered latest spring 26 - University of California, Berkeley.

Midterm 2 Bacterial Pathogenesis Spring 2026: March 19th Professors Dan Portnoy and Russell Vance (MCB103, PMB103) On each page, CAPITALIZE your name in the upper right-hand corner. Write your SID# on the top of this page. Please circle one: MCB103 PMB103 Questions 1-8 TRUE/FALSE: Fill in the box completely for your answers. If you change your answer, put a clear X through the box. (16 points) 1. Which is TRUE of Corynebacterium diphtheriae? (2 points) T F ◻ a. Gram-positive obligate aerobe b. Binds to intestinal cells and elaborates a toxin c. Disease caused by superantigen d. Vaccine consists of toxoid 2. Which is TRUE of Gram-positive cocci? (2 points) T F ◻ a. Low G+C content b. Reside extracellularly c. Motile d. Often part of normal microbiota 3. Which of the following are present only in Gram positive cell wall (2 points) T F ◻ a. Lipoproteins b. Lipid A c. LPXTG proteins d. Peptidoglycan 4. Which is TRUE of Streptococcus pneumoniae? (2 points) T F ◻ a. One serotype causes most human infections b. Salt tolerant c. Antibody to capsule provides protective immunity d. Responsible for millions of annual fatalities 5. Which is TRUE of Bordetella pertussis? (2 points) T F ◻ a. Gram-negative obligate anaerobe b. Grows in alveolar macrophages c. Disease symptoms stop after bacteria are cleared d. Non-motile 6. Which is TRUE of Vibrio cholerae? (2 points) T F ◻ a. Motile b. Causes inflammatory diarrhea c. Obligate pathogen d. Antibodies to Cholera toxin confer long-lasting immunity 7. Which is TRUE of Yersinia pestis? (2 points) T F ◻ a. A single bacterium can kill a mouse b. 99% DNA homology with Yersinia pseudotuberculosis c. Produces a superantigen d. Currently responsible for thousands of annual U.S. deaths 8. Which is TRUE of type III secretion (2 points) T F ◻ a. Present in Gram-positive and Gram-negative bacteria (excluding flagella) b. Mediates secretion of toxins c. Effectors are highly conserved d. Type III apparatus is highly conserved 9. Fill in all of the blanks (18 points) Disease Match from micrographs below (1pt) Name of toxin(1pt) Biochemical mode of toxin action, including target(2pt) Blocked by bafilomycin (Yes or No) (.5pt) Diphtheria Cholera Anthrax Food poisoning A B C D 3 Name (CAPITALIZE):__________________________ 10. You want to evaluate the role of Anthrax lethal toxin in the pathogenesis of Bacillus anthracis infection, but find that some mice are sensitive to the lethal action of the toxin while others are not (7 points) a. What is the cellular basis for sensitivity to killing by the toxin? (2 points) b. Toxin-resistant mice are more susceptible to wild-type anthrax spores than to infection with spores of an anthrax mutant lacking lethal toxin. Explain. (3 points). c. Anthrax spores are highly infectious in humans; predict if you think humans are sensitive or resistant to the toxin? Explain. (2 points) 11. Diphtheria toxin (DT) and Pseudomonas toxin (PT) have the identical enzymatic activity. However, DT acts on human cells but not mouse cells while PT acts on mouse cells but not human cells. Provide a reasonable explanation. How might you use this information to study the pathogenesis of Diphtheria in mice? (4 points) 4 Name (CAPITALIZE):__________________________ 12. Staphylococcus aureus forms golden colonies that is due to the production of a pigment called Staphyloxanthin, as illustrated in the Figure. Transposon mutants in a gene, called crtM, results in loss of golden pigment and virulence in a mouse abscess model, but virulence is restored in mice lacking gp91Phox (6 points) a. What was the hypothesis proposed in class for the role of Staphyloxanthin. (1 point) b. How can you test your hypothesis in mouse cells? (2 points) c. How can you test your hypothesis in human cells (be specific about the source of the human cells)? (2 points) 13. Natural infection with Vibrio cholerae results in the development of long-lived protective immunity (8 points) a. What is the basis of immunity (include the protective antigen in your answer)? (2 points) b. Provide an explanation why a live vaccine strain that lacks Toxin Co-regulated pili (TCP) does not provide effective immunity. (2 points) c. A live vaccine strain lacking cholera toxin A-subunit still caused mild diarrhea. Provide an explanation and how you would use this information to construct a live, safe, and effective oral vaccine. (4 points) 14. In Bordetella pertussis and B. bronchiseptica, BvgA and BvgS are essential for virulence and colonization respectively. (6 points) a. What are BvgA and BvgS? (2 points) b. What is their role in pathogenesis? (2 points) c. What is their role for B. bronchiseptica outside of the host? (2 points) 15. The vaccine for pertussis was changed from a whole bacterial vaccine to a subunit vaccine. During clinical trials, the subunit vaccine was equally protective to the whole bacteria vaccine. Yet, the incidence of whooping cough caused by Bordetella pertussis has increased during the past decade. Assuming that the reason is not lack of vaccination or efficacy of the vaccine to prevent disease, suggest two reasons (one bug-centric and one host-centric) that might explain the increase in pertussis and indicate how you would test each hypothesis (8 points) Host centric: Bacteria-centric: 16. Many bacterial pathogens, such as Yersinia enterocolitica, enter cells that are not normally phagocytic, a phenomenon termed, “invasion.” (10 points) a. Why is the term “invasion,” misleading and what would be a better term? (2 points). b. In a paper discussed in class, the molecular basis of Y. pseudotuberculosis invasion was discovered by simply cloning genes from Y. pseudotuberculosis into a plasmid and transforming E. coli followed by selecting for E. coli strains that were invasive. Invasion was mediated by a single protein. State three reasons why this approach was likely to be unsuccessful for other pathogens. (3 points). 6 Name (CAPITALIZE):__________________________ c. Y. pseudotuberculosis Invasin mutants are defective for invasion of cultured cells and highly defective invading the Peyer’s patches and mesenteric lymph node in the small intestine or orally infected mice. Surprisingly the LD50 and time to death of Invasin mutants is the same as wild-type bacteria. Propose a hypothesis to explain this discrepancy and provide an experiment to test your hypothesis (4 points). 17. Pathogenic strains of Yersinia exhibit calcium dependent growth requirement at 37 ºC. Mutants that are calcium-independent are avirulent and arise at a frequency of approximately 1/1000. Addition of the wild-type strain to macrophages causes the cells to round up, while strains infected with the calcium-independent mutant remain firmly attached to the dish (See Figure). (5 points) a. What is the molecular basis for loss of calcium dependency? (1 point) b. You suspect that the cell rounding is due to a toxin. How would you test this? (1 points) c. Your data from “b.” indicate that that there is no toxin. Based on what you know from class, what would be the effect of the inhibitors below on cell rounding, during infection with Yersinia. For each, indicate how the drug works and choose yes (Y, the cells will round) or no (N, the cells will not round). (3 points)  Y  N 1. Bafilomycin: `  Y  N 2. Gentamicin:  Y  N 3. Cytochalasin D: Questions 18-24 MULTIPLE CHOICE: Fill in the box for the single best answer (2 points ea) (14 points) 18. Which of the following activities is not used by Yersinia effectors to inhibit phagocytosis?  a. protease  b. zipper  c. GAP  d. phosphatase  e. all of the above activities are used by Yersinia effectors to inhibit phagocytosis 19. Which two Yersinia effectors target Rho family GTPases?  a. RhoA and Cdc42  b. YopH and YopM  c. type III and type IV  d. GEF and GAP  e. YopE and YopT 20. Why doesn’t wild-type Yersinia activate the Pyrin inflammasome?  a. it inhibits RhoA  b. it secretes YopE and YopT  c. it secretes YopM  d. it directly inhibits Caspase-1 enzymatic activity  e. it modifies its LPS 21. Which of the following mice would be most likely to survive?  a. wild-type mice infected with wild-type Yersinia  b. wild-type mice infected with ∆yopM mutant Yersinia  c. Pyrin-deficient mice infected with wild-type Yersinia  d. Pyrin-deficient mice infected with ∆yopM mutant Yersinia  e. IL-1 receptor-deficient mice infected with wild-type Yersinia 22.Which of the following types of LPS would most likely fail to activate TLR4?  a. LPS from Yersinia grown at 37°C  b. E. coli LPS  c. LPS from Yersinia grown at 25°C  d. LPS from Yersinia expressing E. coli LpxL  e. Hexa-acylated LPS 23. What does the LpxL enzyme do?  a. inactivates TLR4  b. renders Yersinia avirulent by disrupting the outer membrane  c. modifies the O-antigen of LPS  d. adds acyl chains to LPS  e. prevents Yersinia transmission by fleas 8 Name (CAPITALIZE):__________________________ 24. Why do mice previously infected with the Yersinia pestis pLpxL strain survive a subsequent challenge with wild-type Yersinia pestis?  a. transmission from the flea is blocked  b. because they make a protective immune response  c. because they carry a familial mediterranean fever (FMF) mutation  d. because the Yersinia LPS is modified to be non-stimulatory  e. because Yersinia fails to produce type III secreted effector proteins