✅ M4 - Microbes & Infectious disease Flashcards
What counts as microorganisms? (2 creatures)
- Viruses (nm)
- Genetic element that replicates inside cells
- Sub-cellular parasite (needs to be inside an organism before ‘living’)
- Consist of nucleic acid surrounded by protein
- Classified by type of nucleic acid/how replicate/single or double-stranded - Bacteria (µm)
- Single-celled prokaryotic microorganisms (basic structure)
- No membrane-bound nucleus
What are a few ways (5) for a new disease to emerge or re-emerge today?
(Only focuses on 2-3-6)
- Old diseases known to be microbiological
=> Example: stomach ulcer (Helicobacter pylori) - Old infection re-emerging because it has become resistant to treatment
=> Example: XDR-TB (extensively drug-resistant TB); hospital-acquired infections - Diseases thought to have been eradicated but now re-emerged
=> Example: Syphilis; Chlamydia - A recognised infection spreading to new populations or appearing in new areas
=> Example: Zika /Ebola - A new infection resulting from changes in existing microorganisms
=> Example: Bird/swine flu; SARS - Discovering new tricks & roles for bacteria => potential for usage of gut bacteria in health and disease
How does antibiotic work (name 2 mechanisms and give an example for each)?
- Inhibit cell wall formation (e.g. Penicillin)
- Bacteria usually have peptidoglycan cell wall
- Prevent cross-links (bursting bacterium) - Inhibit protein synthesis (e.g. tetracycline)
- Inhibit 50S and 30S ribosomes that make protein
Why is investing in new antibiotics not attractive commercially?
Problem: In 2020, 41 new antimicrobials were being tested in clinical trials compared to ~1,800 immuno-oncology drugs.
Why?
- Not commercially attractive to invest in new antimicrobials, esp those that target multi-drug-resistant pathogens (“superbugs”)
- Strict controls to restrict their use -> slow the development of resistance.
- Low sales
Solution: UK new payment method -> ensuring a fixed annual fee is paid to the company regardless of how many prescriptions are issued.
What are the mechanisms of antibiotic resistance? Give 5 mechanisms
- Drug impermeability (bacteria’s cell wall is naturally resistant to drug)
- Drug efflux (got pumped out - e.g. mutated ion channel/pump)
- Target modification (structural changes in drug’s target so that the drug won’t work as well)
- Drug inactivation (bacteria releases enzyme that can render drug ineffective)
- Target bypass (
Why it is concerning:
1. One type of antibiotic can be overcome by different mechanisms
2. Different classes of antibiotics can have the same mechanisms of resistance
Why does antibiotic resistance arise?
- Bacteria acquire genes from other bacteria through horizontal transfer of plasmid DNA (bacteria can acquire genetic material from unrelated organisms rather than having to pass through vertical transfer aka reproduction)
- Bacteria grow quickly and mutations can arise very quickly -> eg. Bacteria can repurpose structures (e.g. ion pumps) to remove antibiotics
- Overuse of antibiotics -> e.g. ‘over-the-counter’ meds => easily accessible and widely used
- Animal husbandry (e.g. feeding animals low dose of antibiotics -> promote quick mutation)
- Stopping antibiotics too soon -> e.g. not finishing a dose => not completely eradicate bacteria, allow them to be used to drugs
What are the new approaches to treat bacteria
- Historical:
- Natural compounds (experiment on bacteria sample)
- Semi-synthetic/synthetic => allow mass production of drug from natural compound - Genetic era:
Genome analysis – find homologues / likely candidate genes => develop drugs to clear DNA material in bacteria that makes proteins - Post-genome era:
- Screening libraries of older compounds => make better chemical compound that works better against bacteria
- Systems biology => study how bacteria functions (learn new drug targeting sites) - Other alternatives (what we are focusing on)
- Targeting signal messengers (‘quorum sensing’) between bacteria
- Phage therapy
What is Quorum Sensing and why is it important?
- Essentially a way for bacteria to communicate with each other (usually in a host’s body)
- How it works:
- Bacteria emit chemical signals
- Detect others’ chemical signals to see how many bacteria there are
- If there are enough bacteria, they will initiate their activities. - Why is learning about this important?
- Host/Other species can form symbotic relationship AND ‘cross-talk’ with these bacteria (e.g. Hawaiian bobtail squid)
- Bacteria sending small signalling molecules called ‘autoinducers’ (e.g. small proteins -oligopeptides or RNA molecules)
- Autoinducers bind to receptors on/in bacterial cells which alters gene expression (e.g. bacteria produce toxins or switch off flagella) - Potential new mechanism to control bacterial growth (‘quorum quenching’)
- Interfering with QS signals (so bacteria can survive but not thrive)
- Reduction in antibiotic resistance (slow bacterial growth so takes longer for mutation to happen)
What is meant by bacteriophage therapy?
- What is it and origin?
- Viruses that infect bacteria
- Either via lytic cycle (actively destroys bacteria) OR lysogeny (replicate inside bacteria by copying their genetic material in) - How well does it work?
- Highly specific to a strain of bacteria species
- Used in 1930s
- Lack of efficacy (‘oversold’ properties)
- Superseded by antibiotics - How it was studied?
- In ‘West’: ‘phages studied for Mol. Biol. Research
- In Soviet bloc – cocktails of phage preparations for broad classes of diseases
=> After 1989 came to world’s attention (hampered by lack of translations and incomplete results reports)
Issues with phage therapy?
- Phages are immunogenic (cleared from blood by immune system) => localised use only?
- FDA licensing granted in 2006 for food processing (limited usage)
- Against food-poisoning bacteria (Listeria) for animals
- Disinfectant spray on animal feed (‘GRAS’ licensing) - What about Human use?
- 2007: Small-scale studies against ear infections
- Fully sequenced phages: leg ulcers
- E. coli diarrhoeal disease (Bangladesh)
- 2012: burns victims (military)
=> ‘Compassionate use’: allowed when antibiotics have failed
What are pros and cons of phage therapy?
Pros:
1. Effective in biofilm: can penetrate bacteria’s protective layer (effective against chronic infection)
2. Can avoid killing normal microflora -> phage is only specific to one type of bacteria
3. Use of cocktails (having varieties to treat bacteria) –> less change for bacterial resistance
Cons:
1. Know little about their biology (lack data)
2. Latency problem (some phages just stay in bacteria instead of killing them) -> need careful selection of phages
3. Toxins from phage may affect host cells
4. Strain variation in bacteria species may affect phage therapy effectiveness in destroying them
5. Bacteria can develop resistant to phage
6. Ethical issues (more money if producing antibiotics rather than invest in phage therapy)
Explain an examples of how: an old infection (re-) emerging because it has become resistant to treatment?
Healthcare-associated (nosocomial) infections (HCAIs) => Not all HCAI are preventable
- Micro-organisms (disease) carried by the patient
- Immuno-compromised patients
- Problem bacteria: MRSA a.k.a. ‘Superbug’
—
Examples of nosocomial infections
1. MRSA:
- A bacterium that lives in the skin & throat, may cause skin infections (boils & carbuncles)
- Resistant to many antibiotics (e.g. methicillin)
- CPE:
- Another bacterium that lives in skin & throat, cause immune problems (UTI, pneumonia)
- Resistant to carbapenem antibiotics
Describe the experimental treatment of faecal microbiota transplants (FMT)?
Transfer of microbes from a ‘healthy’ donor to a patient (from feces)
- Result: High success rate (85% cure) for chronic C. diff infections following FMT
- Issues:
- Not defined as to what a healthy microbiome is
- Risks of transmit (e.g. depression/ obesity?) - Ethical implications:
- Changes may affect the local community (microflora)
- Can they be passed to offspring?
Explain an examples of how: diseases thought to have been eradicated but now re-emerged?
- Sexually-transmitted infections: chlamydia/ gonorrhoea/syphilis/ HIV/ herpes/
- Why it is a concern?
- Example: the bacterium that causes gonorrhoea has developed resistance to all antibiotics
- Highest records since 1948 (showing increase in trends)
Describe the features between chlamydia and gonorrhoea?
- Chlamydia:
- Shape/structure: Gram negative cocco/bacili
- Too small - hard to see in light microscope
- Intracellular bacteria (can’t replicate outside cells)
- Primarily infects epithelial cells - Gonorrhoea:
- Shape/structure: Gram negative cocci
- Adhere to epithelial cells of the urethra (men)/cervix (women)
- Some cell invasion (after adherence)
