Week 5 Core

Question 1

What is a DALY?

Answer 1

Disability-Adjusted Life Year = years of life lost to premature death + years of healthy life lost to illness/disability

DALY is a measure used to assess the overall burden of disease.

Question 2

What proportion of all global deaths in 2019 were associated with 33 major bacterial pathogens (excl. TB)?

Answer 2

About 13.6% of all deaths and 56.2% of all infection-related deaths

This highlights the significant impact of bacterial infections on global health.

Question 3

Which five bacteria cause over half of the deaths associated with major bacterial pathogens?

Answer 3

• Staphylococcus aureus
• Escherichia coli
• Streptococcus pneumoniae
• Klebsiella pneumoniae
• Pseudomonas aeruginosa

These pathogens are critical targets for public health interventions.

Question 4

Why are bacterial-pathogen deaths higher in LMICs?

Answer 4

• Poor access to effective antibiotics
• Weak health systems
• Limited prevention (sanitation, vaccination, infection control)

LMICs face unique challenges in managing bacterial infections.

Question 5

Global TB burden (key numbers)?

Answer 5

• ~1.25 million deaths in 2023
• ~10.8 million people developed TB
• ~80% of burden in LMICs

Tuberculosis remains a major global health challenge.

Question 6

Why is TB more common in people with HIV?

Answer 6

HIV causes severe immunosuppression; people with HIV are ≈16× more likely to develop TB

TB is the leading infectious killer among people with HIV.

Question 7

Typical TB treatment duration?

Answer 7

Standard antibiotic regimen lasts ≥6 months

Adherence to treatment is crucial for successful outcomes.

Question 8

What is the estimated global economic cost of AMR bacterial infections?

Answer 8

Roughly $3 trillion per year (≈$53 billion per year in Europe)

Antimicrobial resistance poses a significant economic burden.

Question 9

Approximate average cost to develop a new antimicrobial?

Answer 9

About $1.3 billion

The high cost contributes to the challenges in antibiotic development.

Question 10

On what main factors did WHO base its new bacterial priority list?

Answer 10

• Transmissibility
• Preventability
• Treatability
• Antibacterial pipeline
• Incidence
• Non-fatal burden
• Mortality
• Resistance trends

These factors help prioritize pathogens for research and development.

Question 11

Name at least six WHO priority bacterial pathogens.

Answer 11

• Klebsiella pneumoniae
• E. coli
• Acinetobacter baumannii
• Mycobacterium tuberculosis
• Salmonella Typhi
• Shigella spp.
• Enterococcus faecium
• Pseudomonas aeruginosa
• Neisseria gonorrhoeae
• Haemophilus influenzae
• Streptococcus pneumoniae

These pathogens are prioritized due to their public health impact.

Question 12

What is a primary pathogen?

Answer 12

Causes disease in healthy individuals via specific virulence factors/toxins (e.g. M. tuberculosis, V. cholerae, S. Typhi, Y. pestis)

Primary pathogens are significant in infectious disease.

Question 13

What is an opportunistic pathogen?

Answer 13

Normally harmless but causes disease when defences are impaired or barriers breached (e.g. P. aeruginosa, K. pneumoniae, C. difficile)

Opportunistic pathogens can exploit vulnerabilities in hosts.

Question 14

What is a commensal?

Answer 14

Microbe that normally lives harmlessly as part of the microbiota and can even be protective (e.g. Bacteroides in gut, S. epidermidis on skin)

Commensals play a role in maintaining health.

Question 15

Why doesn’t S. aureus fit neatly into one category?

Answer 15

Can be carried as commensal, act as opportunist (post-injury), and some strains behave like primary pathogens via powerful toxins

Its versatility complicates its classification.

Question 16

Mycobacterium tuberculosis – transmission & reservoir?

Answer 16

Airborne droplets; very infectious; reservoir is humans (no known environmental niche)

Understanding transmission is key for TB control.

Question 17

What is the infectious dose of M. tuberculosis?

Answer 17

Very low – around 3 bacilli

This low infectious dose contributes to its spread.

Question 18

Important virulence factors of M. tuberculosis (3)?

Answer 18

• Mycolic acids
• Cord factor (TDM) promoting granulomas
• ESX-1 secretion system causing phagosomal rupture

These factors enhance its pathogenicity.

Question 19

Vibrio cholerae – main transmission route and classic symptom?

Answer 19

Faecal–oral via contaminated water/food; profuse “rice-water” diarrhoea → severe dehydration

Cholera’s transmission and symptoms are critical for public health responses.

Question 20

Key virulence factors of V. cholerae (3)?

Answer 20

• Flagella (motility)
• Cholera toxin
• Toxin-coregulated pilus (TCP)

These factors are essential for its pathogenicity.

Question 21

Streptococcus pneumoniae – what diseases and who is most affected?

Answer 21

• Pneumonia
• Meningitis
• Otitis media

High mortality in infants and elderly in LMICs.

Question 22

Major S. pneumoniae virulence factors (3)?

Answer 22

• Polysaccharide capsule
• Pneumolysin
• Adhesins

These factors contribute to its ability to cause disease.

Question 23

Why is MRSA a major concern?

Answer 23

Common healthcare-associated pathogen; often resistant to nearly all β-lactams; causes skin infections, pneumonia, sepsis

MRSA poses significant treatment challenges.

Question 24

One important MRSA virulence factor?

Answer 24

Panton–Valentine leukocidin (PVL) – pore-forming toxin

PVL contributes to the severity of MRSA infections.

Question 25

Why is **Pseudomonas aeruginosa** dangerous in hospitals?

Answer 25

Ubiquitous environmental organism, high intrinsic AMR, forms biofilms; severe in burns, CF, ventilated and immunocompromised patients ## Footnote Its resilience makes it a critical concern in healthcare settings.

Question 26

Characteristic **pigment** of P. aeruginosa wound infections?

Answer 26

Blue-green pus due to pyocyanin ## Footnote This pigment is a hallmark of P. aeruginosa infections.

Question 27

Key **P. aeruginosa virulence mechanisms** (3)?

Answer 27

* Exotoxin A * Type III secretion system * Biofilm formation ## Footnote These mechanisms enhance its pathogenicity.

Question 28

Why is **E. coli** both friend and foe?

Answer 28

Normal gut commensal but also leading cause of UTIs, sepsis, neonatal meningitis and diarrhoeal disease via specialised pathotypes ## Footnote Its dual role complicates its management.

Question 29

Yersinia pestis – main forms of **plague**?

Answer 29

* Bubonic * Pneumonic * Septicaemic ## Footnote Understanding these forms is crucial for outbreak response.

Question 30

Y. pestis **transmission routes**?

Answer 30

* Flea bites from rodent reservoir → bubonic disease * Respiratory droplets → pneumonic plague ## Footnote These routes highlight the importance of vector control.

Question 31

One key **Y. pestis virulence mechanism**?

Answer 31

Type III secretion of Yops that block immune responses; plus F1 capsule ## Footnote These mechanisms enhance its pathogenicity.

Question 32

Why is **Neisseria gonorrhoeae** worrying from an AMR standpoint?

Answer 32

Rapidly rising resistance; some strains “super-gonorrhoea” resistant to all first-line drugs; no lasting protective immunity ## Footnote This poses a significant public health challenge.

Question 33

Important **N. gonorrhoeae virulence factors** (3)?

Answer 33

* Type IV pili & Opa proteins (adhesion & antigenic variation) * IgA protease * Porins resisting complement ## Footnote These factors contribute to its ability to evade the immune system.

Question 34

Name four important **bacterial toxins** covered in this week.

Answer 34

* Cholera toxin * Shiga toxin * Botulinum toxin * Pneumolysin ## Footnote Toxins play a critical role in bacterial pathogenicity.

Question 35

What type of toxin is **cholera toxin**?

Answer 35

AB₅ toxin; A = catalytic, B₅ = GM1-binding pentamer ## Footnote Understanding its structure is key to grasping its mechanism of action.

Question 36

Mechanism of **cholera toxin** inside host cells (core cascade)?

Answer 36

A1 subunit ADP-ribosylates Gsα → ↑adenylyl cyclase → ↑cAMP → activates PKA → phosphorylates CFTR → massive Cl⁻ secretion + water → watery diarrhoea ## Footnote This cascade leads to the characteristic symptoms of cholera.

Question 37

Why is profuse diarrhoea a benefit to **V. cholerae**?

Answer 37

Acts as an exit strategy, enhancing transmission in contaminated water ## Footnote This highlights the evolutionary advantages of its virulence.

Question 38

Which organisms produce **Shiga(-like) toxin**?

Answer 38

* Shigella dysenteriae * Shiga-toxin producing E. coli (STEC, e.g. O157:H7) ## Footnote These organisms are significant in causing severe gastrointestinal disease.

Question 39

What type of disease and serious complication does **Stx** cause?

Answer 39

Bloody diarrhoea; can cause HUS (haemolytic-uraemic syndrome) → acute renal failure ## Footnote Understanding these complications is crucial for patient management.

Question 40

What is the enzymatic action of **Shiga toxin A1**?

Answer 40

It is a ribosome-inactivating N-glycosidase that depurinates 28S rRNA → blocks protein synthesis ## Footnote This action is key to its pathogenicity.

Question 41

Source and disease caused by **botulinum toxin**?

Answer 41

Produced by Clostridium botulinum; causes botulism (flaccid paralysis) ## Footnote Botulism is a life-threatening condition requiring immediate medical attention.

Question 42

Basic structure and target of **BoNT**?

Answer 42

Heavy chain (binding + translocation) + light chain Zn²⁺ endopeptidase; cleaves SNARE proteins in cholinergic neurons → blocks ACh release ## Footnote This mechanism leads to the clinical manifestations of botulism.

Question 43

Clinical result of **BoNT** action?

Answer 43

Flaccid paralysis and potential respiratory failure ## Footnote Understanding these outcomes is critical for treatment.

Question 44

What type of toxin is **pneumolysin** and which bacterium produces it?

Answer 44

Cholesterol-dependent cytolysin (CDC) produced by Streptococcus pneumoniae ## Footnote Pneumolysin is a key virulence factor for S. pneumoniae.

Question 45

Two key effects of **pneumolysin** on host cells?

Answer 45

* Pore formation → ion imbalance & cell death * Triggers inflammation and tissue damage, aiding colonisation and transmission ## Footnote These effects enhance its pathogenicity.

Question 46

What problem do **secretion systems** solve for bacteria?

Answer 46

Deliver large protein toxins across bacterial membranes and, in Gram-negatives, into host or other bacterial cells ## Footnote Secretion systems are crucial for bacterial virulence.

Question 47

Type III secretion system (T3SS) – basic description.

Answer 47

Needle-like “molecular syringe” spanning inner & outer membranes of Gram-negative bacteria to inject effector proteins into host cells ## Footnote T3SS is a key mechanism for bacterial pathogenesis.

Question 48

Give one key feature of **T3SS regulation**.

Answer 48

Contact-dependent; triggered by host-cell contact via the needle tip, often sensing pH/Ca²⁺ or mechanical signals ## Footnote This regulation is essential for effective bacterial infection.

Question 49

Type VI secretion system (T6SS) – what does it resemble and what is its main role?

Answer 49

Spring-loaded contractile harpoon; mainly mediates bacterial warfare by injecting toxic effectors into neighbouring cells ## Footnote T6SS plays a role in inter-bacterial competition.

Question 50

How do bacteria avoid killing themselves with **T6SS toxins**?

Answer 50

Each toxin gene is paired with an immunity protein that neutralises its effect inside producer cells ## Footnote This mechanism protects the producing bacteria from self-harm.

Question 51

What was the first widely used **synthetic antimicrobial**?

Answer 51

Sulfonamides (“sulfa drugs”) ## Footnote This marked the beginning of the modern antibiotic era.

Question 52

Which organism gave us most classic **antibiotics** in the “golden age”?

Answer 52

Actinomycetes, especially Streptomyces ## Footnote These organisms are crucial in antibiotic discovery.

Question 53

Roughly when was the last new major **antibiotic class** discovered for clinical use?

Answer 53

Around 1987 ## Footnote This highlights the stagnation in antibiotic development.

Question 54

Why has the **antibiotic pipeline** dried up (2 key reasons)?

Answer 54

* Huge development cost with poor financial return * Scientific difficulty (few new targets, rapid resistance) ## Footnote These factors hinder the discovery of new antibiotics.

Question 55

Define **bactericidal** vs **bacteriostatic** antibiotics.

Answer 55

* Bactericidal: kill bacteria * Bacteriostatic: inhibit growth and replication ## Footnote Understanding these definitions is critical for appropriate antibiotic use.

Question 56

When are **bactericidal drugs** particularly needed?

Answer 56

* Immunocompromised patients * Rapidly life-threatening infections (e.g. sepsis) * Infections in immune-privileged/poorly penetrated sites (CNS, bone, heart valves) ## Footnote These situations require aggressive treatment strategies.

Question 57

Main target and mechanism of **β-lactam antibiotics**.

Answer 57

Bind PBPs (transpeptidases) → inhibit peptidoglycan cross-linking → weakened cell wall → osmotic lysis (bactericidal in growing cells) ## Footnote This mechanism is fundamental to their effectiveness.

Question 58

Binding site and main effect of **aminoglycosides**.

Answer 58

Bind 30S ribosomal subunit at decoding centre → misreading of mRNA + block initiation → faulty proteins + membrane damage → bactericidal ## Footnote This action is crucial for their antibacterial effect.

Question 59

Mechanism of **macrolides**.

Answer 59

Bind 50S near exit tunnel; block translocation and can stall translation on specific peptide motifs → mainly bacteriostatic ## Footnote This mechanism is key to their function.

Question 60

Target and core effect of **fluoroquinolones**.

Answer 60

Inhibit DNA gyrase and topoisomerase IV; stabilise cleaved DNA–enzyme complexes → double-strand breaks, ROS generation → bactericidal ## Footnote This mechanism is essential for their antibacterial activity.

Question 61

What is the **MIC**?

Answer 61

Minimum Inhibitory Concentration: lowest antibiotic concentration that prevents visible growth after incubation ## Footnote MIC is a critical measure in antibiotic susceptibility testing.

Question 62

Why is **MIC** alone not enough to choose therapy?

Answer 62

Must combine with PK/PD, site of infection, drug properties and clinical breakpoints (S/I/R) for that bug–drug pair ## Footnote This comprehensive approach ensures effective treatment.

Question 63

Two broad strategies to get new **antibiotics**.

Answer 63

* Find new scaffolds (natural products, genome mining, AI design) * Improve old ones (medicinal chemistry, adjuvants, better delivery) ## Footnote These strategies are essential for combating antibiotic resistance.

Question 64

Name four **alternatives/adjuncts** to classic antibiotics being explored.

Answer 64

* Phage therapy * Predatory bacteria * Microbiome modulation * Vaccines ## Footnote These alternatives offer potential solutions to antibiotic resistance.