Antibiotics and antifungals Flashcards
state some general features of bacteria
- single cell microorganisms: cell wall, cell membrane
- entire phylogenetic domain
- 1/3 are pathogenic
describe the properties of gram +ve bacteria
- prominent peptidoglycan cell wall
e. g. S Aureus
describe gram -ve bacteria
outer membrane with LPS
e.g. E Coli
describe mycolic bacteria
e.g. M. tuberculosis
outer mycolic acid layer
what are 4 important steps in prokaryotic protein synthesis?
- nucleic acid synthesis
- DNA replication
- RNA synthesis
- protein synthesis
describe nucleic acid synthesis
- PABA –> DHOp (by DHOp synthase)
- DHOp –> DHF
- DHF –> THF (by DHF reductase)
THF important in DNA synthesis
what enzymes are important in DNA replication?
- DNA gyrase/ topoisomerase
- unwinds bacterial DNA, released tension
describe RNA synthesis
- RNA polymerase
- produces RNA from DNA template
describe protein synthesis
- produce protein from RNA templates
- differ from eukaryotic ribosomes
what drugs target nucleic acid synthesis?
- sulphonamides inhibit DHOp synthase
- trimethoprim inhibits DHF reductase
what drugs target DNA replication?
- flurorquinolones inhibit DNA gyrase and topoisomerase
what drugs target RNA synthesis?
Rifamycins inhibit bacterial RNA polymerase
wjat drugs inhibit ribosomes in protein synthesis?
- aminoglycosides
- chloramphenicol
- macrolides
- tetracyclines
what are the 3 steps to bacterial wall synthesis?
- peptidoglycan (PtG) synthesis
- PtG transportation
- PtG incorporation
describe PtG synthesis
- pentapeptide created on N-acetyl muramic acid (NAM)
- N-acetyl glucosamine (NAG) associates with NAM forming PtG
describe PtG transportation
PtG transported across membrane by bactoprenol
describe PtG incorporation
PtG incorporated into cell wall when transpeptidase enzyme cross-links PtG pentapeptides
what drugs inhibit PtG synthesis
glycopeptides bind to pentapeptide preventing PtG synthesis
what drugs inhibit PtG transportation?
- bacitracin inhibits bactoprenol regeneration
- prevents PtG transportation
what drugs inhibit PtG incorporation?
- beta lactams bind covalently to transpeptidase
- inhibits PtG incorporation into cell wall
e. g. carbapenems, cephalosporins, penicillins
what 2 drugs affect cell wall stability (but target cell membrane)?
- lipoprotein - disrupt gram +ve cell membranes
- polymyxins - binds to LPS and disrupts gram -ve cell membranes
what are the causes of antibiotic resistance?
- unnecessary prescription
- livestock farming
- lack of regulation
- lack of development
state the 5 resistance mechanisms
- production of destructive enzymes
- additional target
- alterations in target enzymes
- hyperproduction
- alterations in drug permeation
describe the production of destruction enzymes
- beta lactamases hydrolyse C-N bond of beta lactam ring
- e.g. Pencillins G and V = gram +ve
- flucloxacilin and temocilin are beta lactamase resistant
describe additional target mechanism
- bacteria produce another target that is unaffected by drug
give an example of the additional target mechanism
E coli produce different DHF reductase enzyme making them resistant to trimethoprim
describe alterations in target enzymes
- alteration to enzyme targeted by drug
- enzyme still effective but drug now ineffective
e. g. S Aureus
describe hyperproduction
- bacteria significantly inc. levels of DHF reductase
give an example of a bacteria that uses the hyperproduction method
E coli produce additional DHF reductase enzymes making trimethoprim less effective
describe alterations in drug permeation
- reductions in aquaporins and inc. efflux systems
- primarily of importance in gram -ve bacteria
how can fungal infections be classified?
- superficial: outermost layers of skin
- dermatophyte: skin, hair, nails
- subcutaneous: innermost skin layers
- systemic: primarily resp tract
what are the 2 most common categories of anti-fungals?
- azoles: fluconazole
- polyenes: amphotericin
what do azoles do?
- inhibit cytochrome P450-dependent enzymes involved in membranes sterol synthesis
what is the azole, flucanazole used to treat?
candidiasis and systemic infections
what do polyenes do?
- interact with cell membrane sterols forming membrane channels
what is the polyene, amphotericin used to treat?
systemic infections
