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50 Cards in this Set

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  • Back
What are the 2 residues involved in cross linking of the peptidoglycan cell wall?
meso-diaminopimelioc acid
What are the stages of peptidoglycan synthesis and where do they occur?
Assembly of PG precurssors - cytoplasm
transport to periplasm - membrane
synth of PG polymer - periplasm
What is on the C-term of the polypeptide in PG?
D-ala D-ala
What are the 4 classes of B-lactam antibiotics?
What is the structure of cephalosporins?
b-lactam ring fused with a 6 member ring
What are the R-groups sites of modification in cephalosporins?
1. b-lactamase
2. amidase
3. esterase
What does b-lactamase do in cephalosporin?
C-N inactivation
What does amidase modification do in cephalosporin?
R1 modification
activity against grm +/-
b-lactimase resistance
What does esterase modification do in cephalosporins?
R2 modification
half life of the drug in vivo
Mechanism of transpeptidation is inhibited by?
b-lactam antibiotics
How do b-lactam antibiotics inhibit transpeptidation?
inactivates both enzymes for coavalent cross liniking
What does decreased permeability to a drug do?
mutation in outer memb protiens ie porins is non-specific resistance
What does mutation of penicillin binding protiens do?
increased resistance to drung
ie. strep pneumoniae
What happens when bacteria aquire new DNA that cataylze drug inactivation?
cleavage of b-lactam ring is common due to the action of b-lactimase
often accompanied by resistance to other drugs
What does cycloserine do?
inhibits peptidoglycan synth
cell wall inhibitor
What is the structure of cycloserine?
like D-ala
How ddoes cycloserine work?
competitive inhibitor of D-ala in to sequetional rxns
1. alanine racemase
2. d-ala d-ala synthase
What does vancomycin do?
blocks cross linking of PG
What is vancoymcin's mech of action?
complexes with D-ala
prevents crosslinking
What does vancoymcin work against?
Gram +
When do we use vancomycin?
with penicillin resistance or cephalosporin hypersensitivity
What is vancomycin used to treat?
infection by MRSA (Methocillin Resistant Staph Aureus)
What does bacitracin do?
polypetide that blocks PG biosyth by binding the lipid carrier & preventing it from recycling
What are some reasons cell wall inhibitors are clinically useful?
high selectivity
low toxicity to the host
active against growing bacteria
What type of ribosomes do prokaryotes have?
70S (50 and 30 subunits)
What does tetracyclines do?
bind to P residues on 30S subunit adn interferes with binding of aminoacyl t-RNA to the ribosome
For who is tetracycline active?
BOTH eu and pro
but we deal with them differnetly
How do prokaryotes deal with tetracyclines?
E-dependent transporst that takes it up and it accumulates in the cell causing death
What are 2 ways prokaryotes have developed resistance to tetracycline?
1. actively pumps it out
2. resistant ribosomes
How do aminoglycosides work?
inhibit formation of the 30S initiation complex to decrease the rt of protien synth
What are 2 aminoglycosides?
What is the main problem with aminoglycosides?
limited perm across the outer memb
How do we overcome the main problem with aminoglycosides?
use in combo with b-lactams that disrupt PG to allow more efficient entry of aminoglycosides
How have bacteria formed resistance against aminoglycosides?
covalent modification preventing efficient transport into the bacteria
How do Erthyromycin macrolides work?
binds the 50S ribosome to inhibit its release of deaminoacyl tRNA and inhibits the translocation of peptides
How has resistance to erythromycin come about?
some bacteria can methylate rRNA and erthyromycin cannot bind the methylated rRNA
What type of action does erythromycin have?
bacteriostatic unless at high concentrations then it is bacteriocidal
What is Metronidazole?
inhibitor of DNA which produces radicals to damage DNA used to tx anaerobic bacteria infections
What is the mech of action of Nalidixic acid?
synthetic quinoline that selectively inhibits bacterial DNA gyrase
What is the advatnage to fluorinated quilone (cypro)?
more active than nalidixic acid to inhibit bacterial DNA gyrase
What can cause resistance to quilones?
pt mutation in bacterial DNA gyrase makes it unrecognizable
What is tetrahydorfolate biosythesis?
2 enzyme pathway
used to introduce single Cs into biosynthetic precussors
What 2 drugs block tetrahydorfolate biosynthesis?
What is the mech of action of sulfomides?
inhibits dihydrofolate synthase as a competitive inhibitor to pABA
Why do sulfonamides work?
synthase is unique to bacteria and animals require folic acid for growth
What is the mech of action of trimthoprim?
inhibits dihydrofolate reductase
What is an example of synergy where 2 drugs act to sequentially block a metab pathway?
sulfonamides and trimethoprim
folic acid biosythesis
What is an example of synergy where 1 drug enhances the uptake of another drug?
penicllin and aminoglycosides
What is an example of synergy where 1 drug may prevent the inactivation of another drug?
clavulanic acid inactivates b-lactimase to increase the activity of b-lactam
What is the new drug that inhibits translation and therefore protein synth?