Antibacterial and antifungal agents Flashcards
Bacteria features
- Prokaryotes
- DNA ring like in cytoplasm
- uniform simple structures
Fungi features
Eukaryotes
- DNA separated from cytoplasm by nuclear membrane
- Hyphae, spores
- Complex structures
What features do bacteria and fungi share
Both have:
- Cell wall
- Cell membrane
- DNA
- Synthetic functions (protein synthesis)
What are antibiotics
Chemical products of microbes that inhibit or kill other organisms
Bacteriostatic/ fungistatic
Inhibit growth - protein synthesis inhibitors
Bactericidal/ fungicidal
Kill organism - cell-wall active agents
Minimum inhibitory concentration (MIC)
minimum concentration at which visible growth is inhibited
synergism
activity of 2 antimicrobials given together is greater than the sum of their activity if given separately
Antagonism
one agent diminishes the activity of the other
Antimicrobial targets
- Cell wall
- Protein synthesis
- DNA synthesis
- RNA synthesis
- Cell membrane
Bacterial cell wall
- Peptidoglycan
- Gram +/- bacteria
- Polymer of glucose derivatives
Fungi cell wall
- β-1,3-glucan
- Forms fibrous network on inner surface of the cell wall
β-lactams
- Cell wall synthesis inhibitor
- Targets Transpeptidase enzymes involved in cross-linking the cell wall of bacteria
- β-lactamase enzymes hydrolyse inactive β-lactams
Examples of B lactams
- Penicillins
- Cephalosporins - cefuroxime
- Carbapenems -meropenem
- Monobactams - GRAM - only
Glycopeptides
- Large molecules that inhibit binding of transpeptidases
- Used to treat MRSA
- E.g vancomycin, tigecycline
Antifungal cell wall synthesis inhibitor
- Inhibit β-1,3-glucan synthase
- Echinocandins
- anidulafungin, caspofungin
Bacteria protein synthesis inhibitors function
- Affects the ribonucleoprotein complexes
- Initiation of synthesis happens after 50s and 30s subunits combine - work on these
Bacteria protein synthesis inhibitors
- Aminoglycosides
- MLS antibiotics
- Tetracyclines
- Oxazolidinones
- Mupirocin
- Fusidic acid
Aminoglycosides
Gentamicin - binds to 30s ribosomal subunit
MLS antibiotics
- Macrolides, Lincosamides, Streptogramins
- Macrolides - Clarithromycin
- Lincosamides - Clindamycin for strep
Tetracyclines
- Doxycycline for MRSA
- Binds to 30s and inhibits translation
Oxazolidinones
- Linezolid
- Inhibits initiation of protein synthesis binds to 50s
Why can antifungals not target protein synthesis
Fungi share the same mechanism of protein synthesis to humans
Bacterial DNA synthesis inhibitors
- Trimethoprim
- Sulphonamides
- Quinolones and Fluoroquinolones
Trimethoprim
- Inhibits folate synthesis - Targets dihydrofolate reductase
- Used for UTI’s
Sulphonamides
- Inhibits folate synthesis
- Co-trimoxazole
- Targets dihydropteroate synthetase
Quinolones and Fluoroquinolones
- Inhibit DNA gyrase + topoisomerase IV
- Nalidixic acid effective against bacteria
Fungal DNA synthesis inhibitors
- 5 Fluorocytosine
- selective toxicity is poor
Bacteria RNA synthesis
- Rifamycin e.g. rifampicin: RNA polymerase inhibitor, Prevents synthesis of mRNA
Bacterial cell membrane targeters
- Colistin
- Daptomycin - destroys outer membrane
Fungal cell membrane targeters
- Azoles - oral thrush
- Terbinafine - treats athletes foot
- Amphotericin B - Binds to ergosterol causing physical damage to the membrane. Forces holes in the fungal cell membranes
Antimicrobial combination therapy
- provides broad spectrum
- Increase efficacy - synergistic combos
- Reduce resistance
Fidaxomicin
new antibiotic for C.diff
