Antibiotic Resistance

Question 1

MRSA Vaccine:
What type of bacteria is Staphylococcus Aureus?
→ What does it cause?

What was invented in 1947?

What occurred in 1956? Why did this occur?

What was then invented in 1960?

What then occurred in 1978?

Answer 1

• Gram+ve pyogenic coccus
  → Endocarditis and Sepsis
• Penicillin
• Resistance to Pencillin increased to 70% due to the acquisition of a gene for a β-Lactamase enzyme
• Methicillin (Lactamase-resistant Penicillin)
• Development of Methicillin Resistant S. Aureus (MRSA)

Question 2

What are the 4 ways in which Bacteria can develop Resistance?
→ What is D-ala-D-ala used for?

Answer 2

1. Degradation and Modification of the Antibiotic e.g. β-Lactamase
2. Altered/New target so Antibiotic can’t bind - e.g. PBPs (Penicillin-binding protein)
3. Altered transport of Antibiotic by actively pumping the drug out or not letting it in
4. Metabolic By-pass e.g. In Vancomycin-resistance, there’s a metabolic change of D-ala-D-ALA (into D-ala-D-LAC), so Vancomycin can’t bind
   → D-ala-D-ala is required for the formation of Peptidoglycan cell walls

Question 3

MECHANISMS OF RESISTANCE:
Give an example of Natural Resistance
→ Why are Porins significant in resistance?

Genetic mechanisms:
What is the Chromosome-mediated mechanism?

What is the Plasmid-mediated mechanism?

What are the 2 Non-genetic mechanisms?

Answer 3

• Gram-ve bacteria have an outer membrane, which acts as a barrier to Antibiotics
  → Single mutation of Porins can lead to multiple resistance
• Spontaneous mutations of genes of the target molecule or drug uptake system
  o These mutants have a Selective Advantage when antibiotics are given
• Common in Gram-ve cocci, Transferred via conjugation
• • Drugs can’t get to site of infection
  • Stationary phase and Biofilms - Non-susceptible to inhibitors of cell wall synthesis

Question 4

Gene Transfer:
What can be transferred between bacteria?

What occurs in Transformation?

What occurs in Transduction?

What occurs in Conjugation?

Answer 4

• Virulence (toxins), Drug-resistance, or Antigens (Immunoevasion)
• Uptake of DNA/gene from the environment
• Bacteriophages infect bacteria and transfer its DNA
• Sex pili between the bacteria cells

Question 5

Resistance to β-Lactam Antibiotics (Penicillin):
How can Gram+ve bacteria develop this?

How can Gram-ve bacteria develop this?

What can be added with the β-Lactam drug to make it more effective? What does this do?

Answer 5

• Can alter its PBP (Transpeptidase) and Acquire a β-Lactamase enzyme
• • Alter its Porins so Penicillin can’t reach the PBP
  • Alter its PBP
  • Acquire a β-Lactamase enzyme
• CLAVULANIC ACID - Inhibits β-Lactamase

Question 6

What are some of the ways in which Resistance can be overcome?

Answer 6

• Controlled use - Complete course, Appropriate prescribing
• Combination therapy - Different targets, Overcome mutation rates
• Infection control
• Using new/modified drugs