Antibiotics and antifungals Flashcards
How are bacteria classified?
Based on their membrane properties.
Gram positive bacteria: prominent peptidoglycan cell wall, e.g. Staphylococcus aureus.
Gram negative bacteria: outer membrane with lipopolysaccharide, e.g. Escherichia coli.
Mycolic bacteria: outer mycolic acid layer, e.g. Mycobacterium tuberculosis.
What are the processes involved in nucleic acid synthesis in prokaryotic protein synthesis?
Dihydropteroate (DHOp) produced from paraaminobenzoate (PABA), catalysed by DHOp synthase.
Converted into dihydrofolate (DHF).
Tetrahydrofolate (THF) produced from DHF by DHF reductase.
THF → important in DNA synthesis.
What are the processes involved in prokaryotic protein synthesis?
Nucleic acid synthesis.
DNA replication.
RNA synthesis.
Protein synthesis.
What happens in DNA replication in prokaryotic protein synthesis?
DNA gyrase (topoisomerase) releases tension from DNA molecules.
What happens in RNA synthesis in prokaryotic protein synthesis?
RNA polymerase produces RNA from DNA template, differs from eukaryotic RNA polymerase.
What happens in protein synthesis in prokaryotes?
Ribosomes produce protein from RNA templates, differ from eukaryotic ribosomes.
What are the target molecules of antibiotics that are protein synthesis inhibitors?
Nucleic acid synthesis: dihydropteroate (DHOp), tetrahydrofolate (THF).
DNA replication: DNA gyrase.
RNA synthesis: RNA polymerase.
Protein synthesis: ribosomes.
Which antibiotics target the nucleic acid synthesis stage of prokaryotic protein synthesis?
Sulphonamides inhibit DHOp synthase.
Trimethoprim inhibits DHF reductase.
Which antibiotics target the DNA replication stage of prokaryotic protein synthesis?
Fluoroquinolones (e.g. ciprofloxacin) inhibit DNA gyrase and topoisomerase IV.
Which antibiotics target the RNA synthesis stage of prokaryotic protein synthesis?
The rifamycins (e.g. rifampicin) inhibit bacterial RNA polymerase.
Which antibiotics target the protein synthesis of prokaryotes?
Ribosomes are inhibited by: Aminoglycosides (e.g. gentamycin) Chloramphenicol *Macrolides (e.g. erythromycin)* Tetracyclines
What are the stages of bacterial wall synthesis?
Peptidoglycan synthesis.
Peptidoglycan transportation.
Peptidoglycan incorporation.
What happens in peptidoglycan synthesis?
A pentapeptide is created in N-acetyl muramic acid (NAM).
N-acetyl glucosamine (NAG) associates with NAM, forming peptidoglycan.
How is peptidoglycan transported?
Across the cell membrane by bactoprenol.
How is the peptidoglycan incorporated in to the bacterial cell wall?
When transpeptidase enzyme cross-links peptidoglycan pentapeptides.
What drugs target peptidoglycan synthesis?
Glycopeptides (e.g. vancomycin) bind to the pentapeptide, preventing peptidoglycan synthesis,
Which drugs target peptidoglycan transportation?
Bacitracin inhibits bactoprenol regeneration, preventing peptidoglycan transportation.
Which drugs target peptidoglycan incorporation?
Beta-lactams bind covalently to transpeptidase, inhibiting peptidoglycan incorporation into cell wall. Beta-lactams include carbapenems, cephalosporins and penicillins.
Which drugs target bacterial cell wall stability?
Lipopeptide, e.g. daptomycin, disrupts Gram positive cell walls.
Polymyxins bind to LPS and disrupt Gram negative cell membranes.
What are the causes of antibiotic resistance?
Unnecessary prescription- ~50% of antibiotic prescriptions not required.
Livestock farming- ~30% of UK antibiotic use in livestock farming.
Lack of regulation- OTC availability in Russia, China, India.
Lack of development- very few antibiotics in recent years.
What are the different mechanisms of antibiotic resistance?
Production of destruction enzymes: beta lactamases hydrolyse C-N bond of the beta-lactam ring.
Additional target: different DHF reductase enzyme produced.
Hyperproduction: bacteria significantly increase levels of DHF reductase.
Alterations in drug permeation: reductions in aquaporins (drug influx) and increased efflux systems.
Enzyme alteration: mutations in DNA gyrase enzyme.
How can fungal infections be classified?
In terms of tissues/organs: Superficial- outermost layers of skin Dermatophyte- skin, hair or nails Subcutaneous- innermost skin layers Systemic- primarily respiratory tract
What are the 2 most common anti fungal drugs licensed in the UK?
Azoles, e.g. fluconazole.
Polyenes, e.g. amphotericin.
Give examples of antibiotics that become resisted due to production of destruction enzymes.
Penicillins G & V → Gram positive.
Flucloxacillin and temocillin → beta-lactamase resistant.
Amoxicillin → broad spectrum, Gram negative activity, coadministered with clavulanic acid.
Give an example of an antibiotic-resistant bacterium that becomes resistant due to additional targets being present.
E. coli produce different DHF reductase enzyme making them resistant to trimethoprim.
Give an example of an antibiotic-resistant bacterium that becomes resistance due to an alteration in target enzymes.
S. aureus- mutations in the ParC region of topoisomerase IV confers resistance to quinolones.
Give an example of an antibiotic-resistant bacterium that becomes resistant due to hyperproduction.
E. coli produce additional DHF reductase enzymes making trimethoprim less effective.
Which bacteria are most likely to develop resistance to antibiotics by alteration in drug permeation?
Gram negative bacteria.
What is the action of azoles?
Inhibit cytochrome P450-dependent enzymes involved in membrane sterol (e.g. ergosterol) synthesis.
What are the indications for fluconazole (oral) treatment?
Candidiasis and systemic fungal infections.
What is the action of polyenes?
Interact with cell membrane sterols (e.g. ergosterol), forming membrane channels (create pores).
What are the indications for amphotericin (I-V) treatment?
Systemic fungal infections.
