Antibiotics and antifungals Flashcards
Bacteria
- single cell microorganisms (cell wall and cell membrane included)
- entire phylogenetic domain
- ~ one third are pathogenic
Gram positive bacteria membrane properties
- prominent thick peptidoglycan cell wall
- EG: Staphylococcus Aureus
Gram negative bacteria membrane properties
- outer membrane with lipopolysaccharide
- EG: Escherichia Coli
Mycolic bacteria membrane properties
- outer mycolic acid layer
- EG: Mycobacterium Tuberculosis
Prokaryotic protein synthesis
1) Nucleic Acid synthesis
2) DNA replication
3) RNA synthesis
4) Protein synthesis
Nucleic acid synthesis
1) Dihydropteroate (DHOp)
- produced from paraaminobenzoate (PABA)
- converted into dihydrofolate (DHF)
- sulphonamides inhibit DHOp synthase
2) Tetrahydrofolate (THF)
- produced from DHF by DHF reductase
- important in DNA synthesis
- Trimethoprim inhibits DHF reductase
DNA replication
1) DNA gyrase
- Toposimerase which releases tension in DNA
- Fluoroquinolones (eg: Ciprofloxacin) inhibits DNA gyrase and topoisomerase IV
RNA synthesis
1) RNA polymerase
- produces RNA from DNA template
- differs from eukaryotic RNA polymerase
- rifamycins (eg: Rifampicin) inhibits bacterial RNA polymerase
Protein synthesis
1) Ribosomes
- produces protein from RNA templates
- prokaryotic ribosomes (70S) differ from eukaryotic ribosomes (80S)
- ribosomes inhibited by aminoglycosides (eg: Gentamicin), chloramphenicol, macrolides (eg: erythromycin) and tetracylcines
Bacterial wall synthesis
1) Peptidoglycan synthesis
2) Peptidoglycan transportation
3) Peptidoglycan incorporation
Peptidoglycan synthesis
- pentapeptide is created on N-acetyl muramic acid (NAM)
- N-acetyl glucosamine (NAG) associates with NAM forming peptidoglycan
- Glycopeptides (eg: vancomycin) binds to pentapeptide to prevent peptidoglycan synthesis
Peptidoglycan transportation
- peptidoglycan transported across membrane by bactoprenol
- Bacitracin inhibits bactoprenol regeneration preventing peptidoglycan transportation
Peptidoglycan incorporation
- peptidoglycan incorporated into cell wall when transpeptidase enzyme cross-links peptidoglycan pentapeptides
- Beta-lactams bind covalently to transpeptidase to inhibit peptidoglycan incorporation into cell wall (eg: carbapenems, cephalosporins, penicillins etc)
Cell wall stability
- Lipopeptide (eg: Daptomycin) disrupts gram positive cell walls
- Polymyxins bind to lipopolysaccharides and disrupts gram negative cell membranes
Threat of antibiotic resistance
0~70% of bacteria developed resistance
-25,000 yearly death rate in Europe and the US