BIOC2306 Antibiotics and antibacterial chemotherapy

define antibiotics

natural small mols prod by MO that kill or inhib growth of another

define antibacterial agents/ antibacterials

compounds capable of killing or inhib bac

define antibac drugs

compounds that show selective toxicity against bac vs mammalian cells

can be used in patients

define antibacterial chemotherapy

use of antibacterial drugs to treat bac infections of animals and humans

source of most antibacterial drugs

secondary metabolites from MO (soil bacteria and fungi)

what may the natural role of antibiotics be

signalling

inhib or kill other MOs

nat vs made antibacterial agents

nat often much larger (not penicillin)

first anibacterial agents

penicillin discovered first but sulfonamide first used clinically

what can antibacterials target

cell envelope synth (PG wall or cyto memb)

Nucleic acid synth

Protein synth

common mechanisms of antibacterials

substrate analogues

steric hinderance

enzyme inactivation

mechanism of selective toxicity

target diff in bact and mammals

target absent in mammals

pref accumulation in bact

what 2 main classes target PG synth

beta lactams

peptidoglycans (vancomycin and teicoplanin)

what antibac agents target nucleotide metab

sulfonamides or trimethoprim (inhib enzymes to from THF)

can be used together (co-trimoxazole)

mode of action of sulfa drugs

competitive inhibs and alternate subs for DHPS (dihydropteroate sythase) to prod dead end complex, not tetrahydrofolate

what antibacs target DNA synth

quinolones and fluoroquinolones

target DNA gyrase and Topoisomerase IV (both type 2 topoisomerases)

similarity of DNA gyrase and topoisomerase IV

both A2B2 heterotetramers that cat dsDNA break and rejoin using ATP (supercoil DNA and decantenation respectively)

mode of action of quinolones

stabilise sticky end of dsDNA break, prev reform

how do most antibacterials target protein synth

most act direclty on ribo

most bacteriostatic

majority on 50s subunit

how does linezolid (an oxazolidinone) act on ribo

binds 50sRNA

occupies space norm taken by aa of A site aa-tRNA

holds U2585 of 23s rRNA in cat unfavourable position

how does Fusidic acid act as a protein synth inhibitor in bact

natural steroid like antibiotic

doesnt bind ribo

inhibs correct functioning of elongation factor G (by binding between II and III domains)

causing EFG retain in A site

prev access of incoming aa-tRNA into A site