Lecture 8

Question 1

Who discovered first antibiotic?

Answer 1

Alexander Fleming in 1928

Question 2

What were most early antibiotics

Answer 2

Naturally occurring fungi/bacteria

Question 3

What are antibiotics?

Answer 3

Substances selectively toxic to microorganisms - kill microorganisms without harming patient

Question 4

What bases selective toxicity with bacteria?

Answer 4

Differences in prokaryotes and eukaryotes

Question 5

Describe antibiotic mechanisms

Answer 5

Inhibition of cell wall synthesis e.g. penicillin

Inhibition of protein synthesis e.g. streptomycin

Inhibition of nucleic acid replication and transcription e.g. rifampicin

Injury to plasma membrane e.g. polymyxin A

Inhibition of synthesis of essential metabolites e.g. sulphanilamide

Question 6

How do penicillins kill bacteria

Answer 6

Target peptidoglycan layer in bacterial cell walls

Question 7

Classification of antibiotics

Answer 7

Beta lactam - e.g. Penicillin

Quinolones e.g. ciprofloxacin

Aminoglycosides - Gentamicin

Macrolides - Erythromycin

Tetracyclines - Tetracycline

Glycopeptides - Vancomycin

Sulpha antibiotics - Trimethoprim

Miscellaneous - Rifamycin

Question 8

Bacteriocidal

Answer 8

Bacteriocidal:
- Agents kill bacteria
- Irreversible
- Inhibits cell wall formation
- Doesn’t work with host immune system
- Betalactum antibiotics, vancomycin

Question 9

Bacteriostatic

Answer 9

• Agents prevent bacterial growth
• reversible
• DNA replication and protein synthesis inhibited
• Minimum inhibitory concentration (MIC) - minimum conc to prevent bacterial growth
  -Tetracyclines, spectinomycin

Question 10

3 types of microbial agents

Answer 10

Bacteriostatic

Bacteriocidal

Bacteriolytic

Question 11

Penicillin examples

Answer 11

Penicillin G, Penicillin V, Amoxicillin

• Beta-lactam

Penicillin G discovered first - Derived from Penicillium notatum (fungus)

• Bacteriocidal - Destroy cell wall
• Treat infections e.g. soft tissues, chest infection, pneumonia
• Can cause allergic reactions

Question 12

How do penicillin develop resistance

Answer 12

Beta-lactamase produced - destroys beta lactam ring of penicillin

Interrupts binding of antibiotic - cell wall forms

Question 13

Penicillin mechanism of action

Answer 13

• Interferes with linking enzymes
• NAM subunits remain unattached to neighbours
• Cell grows as NAM and NAG added
• Cell bursts from peptidoglycan integrity not maintained

Question 14

Aminoglycosides

Answer 14

• Bind ribosomes - prevent protein synthesis
• Bactericidal
• Broad spectrum - mainly gram-negative bacteria
• Used for UTIs, intra-abdominal infections, and endocarditis with penicillin
• Side effects: hearing loss, renal impairment

Question 15

How do pathogens develop resistance to aminoglycosides

Answer 15

Altered binding site + efflux pump effect

Question 16

How do aminoglycosides inhibit protein synthesis

Answer 16

• Change 30S shape - mRNA misread
• Block docking site of tRNA
• Chloramphenicol binds
• Lincosamides or macrolides bind 50S subunit, blocking mRNA movement through ribosome

Question 17

Resistance to streptomycin cause

Answer 17

Binding site on ribosome changes shape

Streptomycin cannot bind

Question 18

Tetracyclines

Answer 18

• Prevent bacterial protein synthesis
• Bacteriostatic
• Treat very broad spectrum of gram positives, some gram negative (not Pseudomonas) - Treat skin soft tissue infections, chest infections etc
• Side effects - Affects skeletal development, causes permanent teeth discolouration, photosensitivity

Question 19

Explain metabolism with regards to oral intake of tetracyclines

Answer 19

• Well absorbed after oral administration
• Penetration good into skin, bone, kidney, lung
• Inactivated by liver - excreted in faeces and urine
• Binds calcium and magnesium to form insoluble complex - absorption inhibited by dairy produce

Question 20

Mechanism of tetracycline in preventing bacterial protein synthesis

Answer 20

• Binds A site of 30S ribosomal subunit
• Prevents binding of tRNA to A site
• Prevents protein synthesis
• Bacteriostatic

Question 21

What are the 2 ways tetracycline causes resistance

Answer 21

Tetracycline efflux

Ribosomal protection

Question 22

Tetracycline efflux

Answer 22

• Reduces intracellular concentration of tetracycline in cell by pumping it out
• Efflux protein exchanges proton for tetracycline-cation complex
• Efflux resistance genes found on plasmids
• Resistance gene is a cytoplasmic membrane protein - energy-dependent tetracycline transporter

Question 23

Where are efflux genes found?

Answer 23

Gram positive and negative bacteria

Question 24

Ribosomal protection

Answer 24

9 ribosomal protection proteins: tetM, tetO, tetS, tetW, tetQ, tetT, otrA, tetB, tetC

Interact with ribosome - making it insensitive to tetracycline inhibition

Ribosomal protection proteins bind ribosome and change it’s shape

• Genes for ribosomal protection found on plasmids and self-transmissible chromosomal elements

Question 25

How is tetracycline inactivated

Answer 25

tet(X) gene - tetracycline resistance

tet(X) is 44kDa cytoplasmic protein - modifies tetracycline in presence of oxygen and NADPH

Question 26

Urgent threat pathogens

Answer 26

Clostridoides difficile

Candida auris

Question 27

Serious threat pathogens

Answer 27

Drug-resistant Candida

Drug-resistant Campylobacter

Drug-resistant Streptococcus pneumoniae

Question 28

Concerning threat pathogens

Answer 28

Erythromycin-resistant group A Streptococcus