Flashcards in MGD - Antibiotics Deck (18):
How does erythromycin/gentamicin work?
Inhibits bacterial protein synthesis.
1). Penetrates bacterial cell membrane and binds to an rRNA molecule (50s) near the P site
= prevents tRNA binding
2). It also inhibits peptidyl transferase so translocation of peptides from A site to P site is inhibited = stops cell growth.
How can cells acquire resistance to erythromycin (which inhibits bacterial protein synthesis)?
Vertical or horizontal transmission
In what mechanism may a cell become resistant to erythromycin?
1). Efflux pumps - pumps out erythromycin using ATP before it can bind to rRNA
2). Enzymatic cleavage
3). Target site modification - the ERM gene produces an enzyme which can methylated an adenine residue on the 50s rRNA = erythromycin can no longer bind.
How is erythromycin specific to non human cells?
Human cells do not contain 50S ribosomes.
What are the uses of erythromycin?
Children and adults
How does penicillin/fluclolaxcillin/amoxicilin/cephalexin work?
It inhibits bacterial cell wall synthesis
Bacterial cell walls are strengthened via cross links formed by transferring peptides by transpeptidase.
Penicillin has a ring structure that is a similar shape to the enzymes active site, so binds competitively to transpeptidase permanently = cell can't strengthen wall and therefore lyses.
How may bacteria become resistant to flucloxacillin?
1). Produce beta lactamases which break down the ring structure of penicillin = no longer binds to transpeptidase
2). (Mechanism) The transpeptidase mutates so that penicillin no longer fits.
How is penicillin specific to non human cells?
Human cells do not have cell walls.
What can penicillin be used against?
Gram positive bacteria
How does methotrexate/trimethoprim/metronidazole work?
It is an anti folate in chemotherapy
Competitively inhibits DHFR, an enzyme that synthesises purines and pyramidines to allow the S phase of the cell cycle
= when inhibited, cell growth stops.
How does a cell acquire resistance to methotrexate?
1). Express the DHFR gene more = too much enzyme for the drug to inhibit
2). Express less folate beta receptors on the ell, so they don't take up methotrexate as much.
What is the mechanism in which a cell may become resistant to methotrexate?
1). Rapid mutation of cancer
2). An increase in or mutation in DHFR = too much to inhibit or no longer fits.
3). An increase in lysosomal enzymes hydrolyses methotrexate polyglutamate
4). Lack of polyglutamate (as this is what allows the methotrexate to bind to the enzyme to cause inhibition)
What does methotrexate treat?
How is methotrexate specific?
It has selective affinity for the mammalian form of DHFR
How does rifampicin/ work?
Inhibits bacterial transcription
It binds to the RNA polymerase adjacent to the active site = prevents premRNA from being able to extend further than 2-3 nucleotides long during transcription. This means no premRNA can be formed = can't reproduce or make proteins so dies.
How is rifampicin specific?
Bacteria have 1 RNA polymerase whereas we have many. This means ours have a different amino acid sequence at the drug target area and therefore different conformational shape to theirs = rifampicin can only bind to theirs.
What is the mechanism in which cells may become resistant to rifampicin?
1). Mutation in RNA polymerase = rifampicin can no longer bind
---> this occurs fast, so rifampicin is only used in active infections.