AA antibacterial Flashcards
Describe the cell wall of gram positive and gram negative bacteria
Gram positives have a thick layer of peptidoglycan
Gram negatives have a think layer of peptidoglycan, an outer membrane and a periplasm
Describe the structure of a peptidoglycan
Two sugar derivatives
N-acetylglucosamine (NAG)
N-acetylmuramic acid (NAM)
Variable peptide chain of 4 alternating D and L amino acids connected to NAM
- D-glutamic acid
- D-alanine
- Meso-diaminopimelic acid (DAP)
Chains of polypeptides are crosslinked by tetrapeptide side chains between D-ala to DAP
Outline the 8 stages of peptidoglycan synthesis
UDP derivatives of NAM and NAG are synthesised in the cytoplasm which uses energy
Amino acids are sequentially added to UDP-NAM which forms a pentapeptide
Two terminal D-ala are added
NAM-pentapeptide is transferred from UDP to bactoprenol phosphate at the membrane surface = forms lipid I
UDP-NAG adds NAG to UDP-NAM-pentapeptide to form lipid II
Completed lipid II is transported across membrane by bactoprenol carrier then flipped by flippase enzyme to outside
PG unit is attached to growing PG chain which is catalysed by transglycosylase
Bactoprenol carrier returns to the inside of the membrane
Peptide crosslinks between PG via transpeptidation by transpeptidase
What is transpeptidation
Free amino group of DAP binds to subterminal D-ala
no ATP required
DAP and D-ala form peptide link
What is the mode of action and use of b-lactam antibiotics
Block crosslinking of PG by mimicking D-ala-D-ala terminal. Binding to transpeptidase causes inactivation of the enzymes
Used for growing cells = bactericidal
What are some analogues of b-lactam antibiotics
What are some other cell wall antibiotics
Vancomycin - block transpeptidation
Bacitracin - blocks recycling of C55 bactoprenol lipid carrier
Phosphomycin - blocks synthesis of UDP-NAM
Cycloserin - competitively inhibits enzymes that forms D-ala from L-ala and incorporates D-ala-D-ala
What are macrolides
Inhibit protein synthesis by binding to the 23S rRNA of the 50S ribosomal unit
Inhibit peptide chain elongation by blocking the entrance to the polypeptide export tunnel
Erythromycin
Roxithromycin
Azithromycin
Clarithromycin
What are lincosamides
Inhibits protein sythesis by binding to the 23s rRNA of the 50S ribosomal unit and directly inhibiting peptidyl transferases
Clindamycin
What are chloramphenicol
Binding to the 23s rRNA in the 50S subunit
Peptide bonds don’t form
Streptogamins
Inhibit protein synthesis by binding to 23s rRNA of the 50S subunit at adjacent positions within exit tunnel and block exit tunnel
Synergistic action
Quinupristin
Dalfopristin
Oxazolidinones
Binds to 23S rRNA of 50S subunit
Blocks peptide bond formation
Blocks formation of initiation complex
Linezolid
Tetracyclines
Inhibit protein synthesis by binding to the 30S subunit at the 16S rRNA
Blocks binding of the incoming aminoacyl-tRNA to the A site
Aminoglycosides
Inhibit protein synthesis by binding to the 16s RNA of 30S subunit at the A site
Inhibit translation elongation and make ribosome prone by affecting their proof-reading
- Streptomycin
- Kanamycin
- Gentamicin
- Tobramycin
- Amikacin
- Paromomycin
- Spectinomycin
Quinolones
Inhibit DNA gyrase and/or Topo IV
Binds to DNA gyrase subunits
* Cuts DNA intermediates which accumulates and DNA cannot religate
Halts DNA replication fork
Ciprofloxacin
Norfloxacin
