Block E - Urinary Tract Infections Flashcards
1
Q
Which of the following best describes the structure of the HPV virion?
A) Enveloped icosahedron, 72 capsomers, RNA genome
B) Non-enveloped icosahedron, 72 capsomers, circular dsDNA genome
C) Helical capsid with linear DNA
D) Non-enveloped icosahedron, linear ssRNA genome
A
B
2
Q
What is the function of HPV early proteins E6 and E7 in oncogenesis?
A) E6 stabilizes p53; E7 inhibits EGFR
B) E6 degrades Rb; E7 activates telomerase
C) E6 degrades p53; E7 inactivates Rb
D) E6 activates immune evasion; E7 promotes virion assembly
A
C
3
Q
Which viral feature is essential for HPV replication in the basal layer of the epithelium?
A) Late gene expression via promoter P742
B) High levels of telomerase
C) Early gene expression via promoter P97 and E1/E2 activity
D) Capsid protein expression and assembly
A
C
4
Q
Which of the following best explains why HPV vaccines are non-infectious?
A) They contain inactivated viral DNA
B) They use live attenuated virus strains
C) They contain L1 protein-based VLPs with no viral genetic material
D) They are based on chemically synthesized RNA
A
C
5
Q
Which mechanism most directly contributes to E6 and E7 overexpression in cervical cancer?
A) Alternative splicing of E6/E7 mRNA
B) Mutation in host tumor suppressor genes
C) Disruption of E2 due to viral genome integration
D) Activation of viral capsid gene promoters
A
C
6
Q
Which HPV types are responsible for the majority of cervical cancers?
A) HPV-6 and HPV-11
B) HPV-31 and HPV-45
C) HPV-16 and HPV-18
D) HPV-1 and HPV-2
A
C
7
Q
Which diagnostic method is most appropriate for confirming the presence of cervical intraepithelial neoplasia (CIN)?
A) Papanicolaou test (Pap test)
B) HPV serology
C) Colposcopy with biopsy
D) HPV DNA PCR
A
C
8
Q
Which HPV protein is most directly responsible for telomerase upregulation?
A) L1
B) E2
C) E6
D) E7
A
C
9
Q
Which of the following is a characteristic of the HPV genome?
A) Linear ssRNA with early and late regions
B) Circular dsDNA ~8kb with a single transcription strand
C) Segmented RNA genome with multiple promoters
D) Non-coding RNA genome with no capsid proteins
A
B
10
Q
What is the recommended HPV vaccination schedule in the UK as of 2024?
A) Three doses over one year
B) Two doses in year 8, one year apart
C) Single dose in year 8 following JCVI guidance
D) Four doses over two years
A
C
11
Q
Which HPV gene is responsible for viral genome replication and helicase activity?
A) E2
B) E1
C) L2
D) E6
A
B
12
Q
Which of the following statements about HPV transmission is TRUE?
A) HPV is transmitted via respiratory droplets
B) HPV requires blood-to-blood contact
C) HPV is epitheliotropic and transmitted via direct contact
D) HPV is transmitted through contaminated food
A
C
13
Q
What cellular receptor is most likely involved in HPV binding to host epithelial cells?
A) CD4
B) ACE2
C) Heparan sulfate proteoglycans (HSPGs)
D) Integrins
A
C
14
Q
What is the role of the L2 protein in the HPV life cycle?
A) Binds and inactivates Rb
B) Initiates DNA replication
C) Assists genome trafficking to the nucleus
D) Forms the viral capsid shell
A
C
15
Q
Which best describes the composition of the L1-based VLP HPV vaccines?
A) Live attenuated virus containing all HPV genes
B) Recombinant L1 protein assembled into virus-like particles
C) Heat-inactivated whole virus
D) Synthetic RNA encapsulated in lipid nanoparticles
A
B
16
Q
What is the role of the E2 protein in regulating HPV oncogene expression?
A
E2 represses transcription of E6 and E7; its disruption during integration leads to oncogene overexpression.
17
Q
Why does HPV specifically infect basal epithelial cells rather than superficial ones?
A
Basal cells are mitotically active, allowing the virus to access host replication machinery.
18
Q
Describe how the integration of HPV DNA into the host genome contributes to carcinogenesis.
A
Integration often disrupts E2, removing its repression on E6/E7, which promotes uncontrolled cell proliferation.
19
Q
Why is the L1 protein used in HPV vaccines instead of the full virus?
A
L1 forms virus-like particles that are non-infectious but immunogenic, ensuring safety while inducing immunity.
20
Q
How do HPV-16 and HPV-18 contribute differently to cancer compared to HPV-6 and HPV-11?
A
HPV-16/18 are high-risk oncogenic strains, while HPV-6/11 cause benign lesions like genital warts.
21
Q
Explain the significance of CIN3 in the progression to cervical cancer.
A
CIN3 involves full-thickness epithelial dysplasia and has the highest risk of progression to invasive carcinoma.
22
Q
What is the role of host cell differentiation in the HPV replication cycle?
A
HPV relies on epithelial cell differentiation for late gene expression and virion assembly in upper layers.
23
Q
Why is the HPV vaccine still recommended for people who are already sexually active?
A
It can protect against HPV types the person hasn’t yet encountered, providing partial but important protection.
24
Q
Describe one diagnostic method for detecting HPV and its clinical utility.
A
HPV DNA PCR detects high-risk HPV types and is used in cervical screening to assess cancer risk.
25
How does E6 promote telomerase activity and what is its significance in immortalization?
E6 upregulates hTERT, maintaining telomere length and enabling cells to divide indefinitely.
26
A woman has an abnormal Pap smear (suggestive of CIN2), but her HPV DNA test is negative. What are two possible reasons for this discrepancy, and what should be the next step in management?
Possible reasons: false-negative HPV test, lesion caused by a non-detected HPV type. Management: colposcopy with biopsy for confirmation.
27
A parent is concerned about the safety of the HPV vaccine and asks whether it can cause infection. How would you explain the structure of the vaccine and why it cannot cause HPV infection?
The vaccine uses virus-like particles (VLPs) made of L1 protein, without any viral DNA, so it cannot replicate or cause infection.
28
A patient has tested positive for HPV-16 three times over two years. What risk does this pose, and what is the clinical implication of persistent infection with a high-risk strain?
Persistent HPV-16 infection increases the risk of high-grade CIN and cervical cancer; close monitoring and colposcopy are recommended.
29
A biopsy shows koilocytosis and dysplastic basal cells consistent with CIN1. What does this indicate about the stage of HPV infection, and how should this patient be followed up?
CIN1 suggests early-stage HPV-induced dysplasia; most cases regress spontaneously. Follow-up in 12 months with repeat screening is appropriate.
30
A girl received one HPV vaccine dose, but new UK guidance recommends one dose. Is a second dose still needed?
No; under updated JCVI guidelines, a single dose is sufficient for immunocompetent adolescents. No further doses are required.
31
Which of the following best explains the dual binding behavior of FimH in UPEC?
A) FimH switches between S-bound and A-bound states to resist immune responses
B) FimH alternates conformations to enable movement and strong adherence under shear stress
C) FimH only binds to uroplakin during infection onset
D) FimH is inactive during high shear stress to evade host defenses
B
32
In the context of catheter-associated UTIs, what is the primary role of fibrinogen?
A) Fibrinogen facilitates neutrophil recruitment
B) Fibrinogen neutralizes bacterial adhesins
C) Fibrinogen provides a binding substrate for UPEC adhesins, promoting biofilm formation
D) Fibrinogen forms a protective layer preventing UPEC colonization
C
33
Why do certain UPEC strains like HM7 retain virulence despite encoding fewer siderophore systems?
A) They produce excessive host-derived iron
B) They use alternative iron sources like ferric citrate via a dedicated transport system
C) They rely on the host microbiota for siderophore production
D) They exhibit enhanced biofilm resistance
B
34
Which factor most accurately contributes to UPEC persistence within host bladder tissue following acute infection?
A) Continuous expression of P-fimbriae
B) Formation of intracellular bacterial communities in the kidney
C) Development of quiescent intracellular reservoirs (QIRs) post-exfoliation
D) Overproduction of Type I fimbriae
C
35
How do mannosides function as a non-antibiotic treatment against UPEC infections?
A) They degrade UPEC pili to prevent colonization
B) They mimic mannose to competitively inhibit FimH-mediated adhesion
C) They promote macrophage activation
D) They disrupt bacterial DNA synthesis
B
36
Which E. coli pathotype is most commonly associated with urinary tract infections and what feature distinguishes it?
A) ETEC; presence of heat-labile enterotoxin
B) EHEC; production of Shiga toxin
C) UPEC; expression of specific adhesins like type 1 and P fimbriae
D) EPEC; formation of attaching and effacing lesions
C
37
Which of the following scenarios would be classified as a complicated UTI? A) A young healthy woman with a single episode of cystitis
B) A male with UTI but no other risk factors
C) A pregnant woman with signs of pyelonephritis
D) A child presenting with asymptomatic bacteriuria
C
38
P-fimbriae are specifically associated with which UTI complication and what is their host binding target?
A) Urethritis; sialylated glycolipids
B) Cystitis; mannose-containing receptors
C) Pyelonephritis; globoside in the kidney
D) Bacteraemia; CD55
C
39
Which feature of curli fibers in UPEC biofilms makes them particularly resistant to immune clearance?
A) Secretion of toxins within the matrix
B) Their amyloidogenic structure forming dense extracellular fibers
C) The incorporation of host cells into biofilms
D) Enhanced motility in biofilms
B
40
What is a defining feature of UPEC intracellular bacterial communities (IBCs) in the early phase?
A) Rapid switching to coccoid form upon entry
B) Tight clusters of motile rod-shaped bacteria
C) Loosely organized colonies of rod-shaped bacteria
D) Immediate formation of filamentous bacteria
C
41
What is the role of filamentous UPEC forms observed in the bladder lumen during infection?
A) They increase susceptibility to neutrophil attack
B) They serve as a dormant stage for long-term survival
C) They promote bacterial dispersal and evade neutrophil clearance
D) They invade deep kidney tissues
C
42
Which combination of non-antibiotic treatments directly prevents UPEC adhesion to urothelial cells?
A) Vitamin D and NSAIDs
B) Cranberry extract and D-mannose
C) Probiotics and methenamine hippurate
D) Ibuprofen and oestrogen therapy
B
43
Which challenge is most critical in designing vaccines against UPEC?
A) Identifying virulence genes shared with non-pathogenic strains
B) Targeting proteins involved in antibiotic resistance
C) Finding conserved, surface-exposed antigens recognized by the immune system
D) Ensuring UPEC strains can be cultured in lab conditions
C
44
How does Lactobacillus in the genitourinary tract protect against UPEC colonization?
A) Neutralizes siderophores released by UPEC
B) Promotes inflammation to expel pathogens
C) Occupies adhesion sites and produces inhibitory compounds
D) Triggers exfoliation of umbrella cells
C
45
Why does empirical antibiotic use in UTIs contribute to antimicrobial resistance?
A) It completely eradicates non-pathogenic strains
B) It delays the onset of infection symptoms
C) It selects for resistant bacteria due to treatment before culture results
D) It increases iron availability to bacteria
C
46
Explain the role of FimH in UPEC adhesion and how its binding conformation changes in response to urine flow. (7 marks)
-FimH is the tip adhesin of type 1 fimbriae and binds to mannosylated glycoproteins like uroplakin.
-It has a unique catch bond ability which strengthens the bond under force. When urine flow increases, it pulls on the FimH proteins.
-This causes FimH to change its comformational shape to one that grips more tightly.
-FimH has two domains, the lectin domain and the pilin domain.
-In low force the lectin domain is covered by the pilin domain, so it cant bind to mannose well.
-The high force pulls both domains apart, relaxing the lectin domain into its proper shape.
-This opens up the mannose binding site and makes it fit perfectly into a lock and key conformation, strengthening the bond
-this lets UPEC resist the defence mecahnism of urine flow
47
Describe the mechanisms by which UPEC establishes chronic infections in the bladder.
UPEC invades superficial bladder epithelial cells and forms intracellular bacterial communities (IBCs). After exfoliation, they establish quiescent intracellular reservoirs (QIRs) that can persist and reactivate, leading to recurrent infections.
48
What are the key differences between uncomplicated and complicated UTIs?
Uncomplicated UTIs occur in otherwise healthy individuals, typically limited to the lower urinary tract. Complicated UTIs involve risk factors such as pregnancy, catheter use, or immunosuppression, and can affect the upper urinary tract including kidneys.
49
A patient presents with recurrent UTIs, and urine culture shows UPEC even during asymptomatic periods. What two potential reservoirs should be considered, and how might treatment be tailored?
Potential reservoirs include the gastrointestinal tract and quiescent intracellular bladder reservoirs. Treatment might include probiotics to modulate the gut microbiome and therapies targeting intracellular UPEC or adhesion-blocking strategies like D-mannose.
50
You are developing a new anti-adhesive therapy for UPEC. What molecular target would you prioritize and why? (6 marks)
-FimH should be prioritized because it binds to mannosylated glycoproteins on host cellst, particularly uroplankins on bladder cells.
-This binding allows UPEC to resist being flushed by urine flow and helps invade bladder epithelial cells, initiating infection and forming IBCs.
-it also triggers host cell uptake of bacteria by manipulating cytoskeletal pathways.
-it is a key target for preventing colonization and biofilm formation.
-FimH is a bacterial protein thats highly conserved in UPEC, so its a reliable target that minimises disruption to host cells.
-FimH is located on the tip of type 1 pili, making it structurally exposed and easily targetable by inhibitors, antibodies, or small molecules.
51
How might you design a clinical intervention for catheter-associated UTIs that addresses both inflammation and biofilm formation?
-design catheters with antibiofilm agents such as FimH antagonists (mannosides) to prevent adhesion of UPEC or quorum sensing inhibitors to prevent biofilm formation (LuxS inhibitors)
-Coat it in anti-inflammatory agents like NSAID derivertives to reduce local inflammation and IL-10 mimetics to to dampen pro-inflammatory cytokines like IL-6, TNF-alpha
52
Which feature of Candida albicans most directly contributes to its ability to invade host tissues and cause systemic infection?
A) Ergosterol biosynthesis
B) Yeast cell budding
C) Pseudohyphal formation
D) Biofilm production
C
53
Candida auris presents a significant clinical challenge because:
A) It is only found in tropical climates
B) It is susceptible to most antifungals
C) It is often multidrug-resistant and can spread in hospitals
D) It only affects immunocompetent individuals
C
54
Which of the following antifungal drug classes acts by inhibiting chitin synthesis in Candida albicans?
A) Azoles
B) Echinocandins
C) Polyoxins
D) Polyenes
C
55
Candidemia is most likely to occur in:
A) Healthy individuals following minor surgery
B) Immunocompetent hosts using probiotics
C) Hospitalized, immunocompromised patients with indwelling devices
D) Patients taking a single dose of antifungal medication
C
56
Which mechanism underlies azole resistance in Candida species?
A) Microtubule stabilization
B) Disruption of chitin synthesis
C) Inhibition of 5-fluorocytosine metabolism
D) Mutations affecting ergosterol synthesis
D
57
Which statement best describes the epidemiology of Candida auris?
A) First identified in the US and remains isolated there
B) Found worldwide with genetically distinct clades by region
C) Only associated with superficial skin infections
D) Limited to patients with gastrointestinal symptoms
B
58
Which Candida albicans infection is most likely to affect immunocompetent individuals?
A) Candidemia
B) Invasive candidiasis
C) Thrush (oropharyngeal candidiasis)
D) Ocular candidiasis
C
59
Griseofulvin is used against Candida infections by targeting:
A) Membrane sterols
B) DNA replication
C) Microtubule formation
D) Glucan synthesis
C
60
A patient undergoing chemotherapy presents with fever and chills unresponsive to antibiotics. Blood cultures later confirm candidemia. What are two likely risk factors and what antifungal treatments should be considered?
Risk factors include immunosuppression from chemotherapy and possible presence of indwelling devices (e.g. catheters). Systemic antifungal treatments such as echinocandins or amphotericin B are first-line options.
61
A hospital outbreak involves multiple patients in ICU testing positive for Candida auris. Some isolates are resistant to fluconazole. As a clinical microbiologist, what immediate steps should be taken to control this outbreak?
Isolate infected/colonized patients, enhance environmental disinfection protocols, perform contact tracing, screen other high-risk patients, and review antifungal treatment regimens considering potential multidrug resistance.
62
A woman presents with recurrent vulvovaginal candidiasis. Cultures confirm Candida albicans. She is otherwise healthy. What are two possible contributing factors and what non-pharmacological advice would you give?
Contributing factors may include high sugar/starch diet or recent antibiotic use. Advise on good hygiene, reducing sugar intake, and consider probiotic use to restore microbiota balance.
63
A patient has white plaques in the mouth, difficulty swallowing, and is HIV-positive. What type of candidiasis is this, and why is this patient more susceptible?
This is likely oropharyngeal or esophageal candidiasis. The patient is immunocompromised due to HIV, which allows Candida albicans to overgrow and become pathogenic.
64
Define dimorphism in the context of Candida albicans and explain its relevance to pathogenicity.
Dimorphism refers to the ability of C. albicans to switch between yeast and filamentous (hyphal/pseudohyphal) forms. This transition is associated with tissue invasion and virulence.
65
Explain how echinocandins act against Candida albicans and why they are preferred for invasive infections.
Echinocandins inhibit β-glucan synthesis in the fungal cell wall, weakening the structure and leading to cell lysis. They are fungicidal, especially effective in bloodstream and systemic infections.
66
Why is Candida auris classified as a major global health threat by the CDC?
Because it is often multidrug-resistant, difficult to identify with standard lab methods, survives well in healthcare environments, and causes severe, hard-to-treat infections in vulnerable patients.
67
What role does antibiotic use play in the development of candidiasis?
Antibiotics can disrupt normal bacterial flora that keep Candida in check, allowing overgrowth and infection, particularly in mucosal areas like the vagina and oral cavity.
68
Which organism is most consistent with the following lab profile: purple cocci, pale yellow colonies, arranged in clusters, coagulase-positive, catalase-positive, produces P-V leukocidin?
A) Streptococcus pyogenes
B) Staphylococcus aureus
C) Escherichia coli
D) Enterococcus faecalis
B) Staphylococcus aureus
69
Which of the following toxins produced by S. aureus is responsible for damaging host leukocytes and is associated with skin and soft tissue infections?
A) Alpha-toxin
B) Beta-toxin
C) Panton-Valentine leukocidin (PVL)
D) Delta-toxin
C) Panton-Valentine leukocidin (PVL)
70
What is the method most commonly used to repeat antibiotic sensitivity testing when previous results were inconclusive?
A) MIC broth dilution
B) Kirby-Bauer disc diffusion
C) ELISA
D) PCR
B) Kirby-Bauer disc diffusion
70
What selective and differential medium is typically used to distinguish between S. aureus and S. epidermidis?
A) Blood agar
B) Nutrient agar
C) MacConkey agar
D) Mannitol salt agar
D) Mannitol salt agar
71
Which of the following best explains how influenza viruses generate new pandemic strains?
A) Antigenic drift via point mutations in hemagglutinin
B) Recombination with bacterial genomes
C) Antigenic shift via reassortment of RNA segments
D) Genetic fusion with host chromosomes
C) Antigenic shift via reassortment of RNA segments
72
What key biochemical features define Staphylococcus aureus?
Catalase-positive and coagulase-positive; catalase differentiates Staphylococci from Streptococci; coagulase distinguishes S. aureus from other Staph species.
73
Why does Mannitol Salt Agar produce different colours with different Staphylococcus species?
It contains mannitol and phenol red. S. aureus ferments mannitol → acid → yellow colour; S. epidermidis does not ferment mannitol → stays pink.
74
How does Panton-Valentine leukocidin contribute to pathogenesis?
PVL forms pores in the membranes of leukocytes, leading to lysis and enhanced inflammation; associated with necrotising infections.
75
What is the genetic structure of the Influenza virus?
It is a segmented, negative-sense ssRNA virus with 8 segments, allowing reassortment and emergence of new strains via antigenic shift.
76
Name one major difference in gene expression between trypanosomatids and higher eukaryotes.
Trypanosomatids use polycistronic transcription and trans-splicing, unlike monocistronic transcription in higher eukaryotes.
77
A patient presents with local swelling and redness around a urinary catheter insertion site. Lab cultures show Gram-positive cocci in clusters that are catalase- and coagulase-positive.
Q: Identify the organism. What virulence factors are likely contributing to this infection?
Staphylococcus aureus. Virulence factors include Protein A (immune evasion), alpha-toxin (pore formation), and P-V leukocidin (kills leukocytes).
78
A patient presents with abdominal cramps and diarrhoea. Lab results show high counts of a Gram-negative bacillus in stool.
Q: How would you identify the organism and determine appropriate treatment?
Identification: Culture on MacConkey agar, oxidase test, PCR for toxin genes (e.g., shiga-toxin). Treatment: Supportive therapy; antibiotics only if severe or systemic (e.g., ciprofloxacin, but not for STEC due to HUS risk).
79
You're asked to brief hospital staff on the emergence of a new H7N9 strain.
Q: Why is this strain a concern and what features of the influenza genome allow such pandemics to arise?
The segmented genome allows antigenic shift through reassortment. A novel H7N9 could have limited pre-existing immunity in the population, increasing pandemic risk.
80
An ICU patient on broad-spectrum antibiotics develops fever and is diagnosed with candidemia.
Q: What factors predispose patients to candidemia, and how is it diagnosed and treated?
Risk factors: central venous catheters, antibiotics, immunosuppression. Diagnosis: blood culture, beta-D-glucan test. Treatment: echinocandins or fluconazole.
81
Are yeasts Gram-positive or negative?
gram-positive
82
What is it about Mannitol Salt Agar that makes it selective for staphylococcus spp.? (2 marks)
-MSA contains 7.5% of sodium chloride, which is a high salt concentration
-this inhibits most bacteria except salt tolerant bacteria like Staphylococcus species
83
What is it about Mannitol Salt Agar that makes it differential to staphylococcus aureus? (2 marks)
-Mannitol salt agar contains mannitol and phenol red (PH indicator).
-S. aureus ferments mannitol, producing acid. this acid causes phenol red to turn the colonies yellow around the colonies
84
What is xylose lysine deoxycholate agar selective and differential for? (1 mark)
-differential and selective for Salmonella and Shigella in enteric cultures
85
Name one medium that is selective for mycobacterium?
Lowenstein-Jensen medium
86
What is FimH (2 marks)
-it is a mannose-binding adhesin located at the tip of type 1 pili on the surface of UPEC.
-It is critical for the initial attachment of the bacteria to the urothelial cells lining the bladder, which is the first step in establishing infection in urinary tract infections (UTIs)
