Lec 3- Cell wall (2)

Question 1

Sites of action of anti-bacterial agents- Ribosome (protein synthesis)

Answer 1

• Aminoglycosides-Gentamicin
• Tetracyclines- oxytetracycline
• Chloramphenicol
• Macrolides- clarithromycin
• Azalides- azithromycin
• Lincosamides- Lincomycin
• Oxazolidinones-
• Mupirocin
• Fudisic acid
• Pleuromutillins- retapamulin

Question 2

Sites of action of anti-bacterial agents- Metabolic (DNA synthesis)

Answer 2

• Anti-folate- lamotrigine
• Sulphonamides-
• Trimethoprim

Question 3

Sites of action of anti-bacterial agents- Cell wall synthesis

Answer 3

• B-Lactams- amoxicillin, cephalosporin C
• Glycopeptides- Vancomycin

Question 4

Sites of action of anti-bacterial agents- Chromosome (DNA replication)

Answer 4

• Quinolones-
• Rifampicin
• Nitroimidazole
• Nitrofurans

Question 5

Sites of action of anti-bacterial agents- Cell membrane disruption

Answer 5

• Polymyxins
• Daptomycin

Question 6

Structure

Question 7

Carbapenems

Answer 7

• Thienamycin is a naturally produced carbapenem antibiotic (Streptomyces)- most potent to date
• Broad spectrum (G+ and G-) and resistant to b-lactamase
• Can be chemically modified to a range of semi-synthetic carbapenems
  
  • Imipenem (sensitive to renal peptidase)
  • Meropenem (resistant to renal peptidase)

Question 8

Monobactams

Answer 8

• Nocardicin A is a naturally produced monobactam b-lactam anti-biotic
• Aztreonam is a synthetic monobactam resistant to b-lactamases and is the only clinically used monobactam
• Often tolerated by patients who have hypersensitivity to penicillins

Question 9

Adverse drug reaction

Answer 9

• Mild adverse drug reaction (ADR)(Hypersensitivity) to penicillins occurs in about 1% of patients (diarrhoea, nausea, rash)
• 10% tend to report some of these effects but these are often not related to the penicillin
• This is a type I response (IgE)
• Believed to be due to haptenization of proteins
• Cross-sensitivity is low between classes
• Severe anaphylaxis occurs in around 0.1% mechanism is unclear
  *

Question 10

Glycopeptide antibiotic

Answer 10

• Vancomycin is a naturally produced by glycopeptide antibiotic (initially isolated from Nocardia Orientalis)
• Now produced by fermentation
• Biosynthesis by unusual non-ribosomal peptide synthesis
• Effective against G+ bacteria- cannot pass additional membrane of G-ve
• red= sugar (glyco)
• Green= Peptide (peptide- lots of AA bonded with amide bond)

Question 11

Glycopeptide antibiotics

Answer 11

• Teicoplanin is another example of a naturally produced glycopeptide antibiotic (Actinoplanes teichomyceticus)
• Teicoplanin is a mixture of (at least) 5 compounds with the same glycopeptide core- difficult to get past regulatory bodies

Question 12

Glycopeptide bind to D-ala-D-ala

Answer 12

• Glycopeptide antibiotics block the formation of the peptidoglycan in 2 ways:
  
  • Preventing the formation of linear glycan (NAG-NAM) strands by transglycosylase
  • Inhibiting peptide cross-linking by transpeptidase
• They do this by binding tightly to the terminal D-alanyl-D-alanine of the peptidoglycan by hydrogen bonding- due to cage-like shape so D-alanine fits very well- transpeptidase can’t bind
• Because they don’t get used up (don’t open up ring), so can do many reactions and so continue to bind
• Used for the resistant organism- is starting to emerge but this is very weak, it is hard to come up with resistance because it’s not a covalent reaction
  *

Question 13

Detail Gram-positive cell wall structure

Answer 13

• Transpeptidase- removes terminal D-alanine and cross-links the peptides with pentaglycine
• Transglycosylase- extends the glycan chains
  
  • Glycopeptide anti-biotics also inhibits the glycan chain
• Anti-biotics come to have to come up with 2 different mechanisms of resistance to become effective against glycoprotein anti-biotic making it even harder

Question 14

Mode of action of vancomycin

Answer 14