Antibiotic: Protien Synthesis inhibitors

Question 1

What is the MOA of macrolides

Answer 1

Inhibits protein synthesis when specific mRNA sites are present that would lead to certain amino acid sequences

Question 2

What are the common macrolides

Answer 2

Clarithromycin, Azithromycin, Roxithromycin

Question 3

T/F: The first macrolide antibiotic was erythromycin

Answer 3

True

Question 4

What gram stain type of bacteria do macrolides work best on

Answer 4

Gram positive

Question 5

What was the main problem with 1st generation macrolides

Answer 5

At acidic pHs they would become unstable and convert into an inactive ketal

Question 6

What subunit do macrolides bind to, where on the this subunit does it cause problems

Answer 6

Large subunit, nascent protein tunnel

Question 7

What part of macrolides binds to ribosome, with is the nucleotide that is bound

Answer 7

Desosamine binds to A2058

Question 8

What structure changes of third generation macrolides make them improved

Answer 8

alkyl-aryl side chain of ketolides make additional contacts with the ribosome, increasing affinity of the drug

Question 9

What are the three main types of antibiotic resistance

Answer 9

Ribosome modification, drug efflux, ribosome protection

Question 10

T/F: Mutations in rRNA are rare and occur mostly in organisms with low copy numbero of rRNA genes

Answer 10

True

Question 11

What is the most frequent mechanism of macrolide resistance

Answer 11

Dimethylation of A2058 by Erm

Question 12

What is the protein that actively removes macrolides from their site of action

Answer 12

MrsE

Question 13

What is the MOA of oxazolidinones

Answer 13

Binds the peptidy transferase center preventing the initiation of translation

Question 14

What are the two common oxazolidinones

Answer 14

Linezolid and Tedizolid

Question 15

What gram stain type of bacteria do oxazolidinones work best on

Answer 15

Gram positive

Question 16

What subunit does oxazolidinones bind to, where on that subunit, what specifics need to be present for binding

Answer 16

Large subunit, the peptidyl transferase center, a penultimate alanine on the growing peptide

Question 17

What is the main adverse effect that comes from using oxaolidinones, why

Answer 17

reversible myelosuppression, mitcohondria rRNA are quite similar to bacterial rRNAs and therefore are also effected

Question 18

What are the genes that lead to oxazolidinone resistance, what can their expression lead to

Answer 18

cfr, methylation of A2503

Question 19

T/F: Expression of erm and cfr genes could lead to resistance to all clinical antibiotics that target the large ribosomal subunit

Answer 19

True

Question 20

What is the MOA of lincosamides

Answer 20

Binds near the peptidyl transferase causing a steric hinderance that inhibits the elongation causing premature dissociation

Question 21

What is the most used lincosamide

Answer 21

Clindamycin

Question 22

What gram stain does lincosamide (clindamycin) antibacterials work on

Answer 22

Gram positive

Question 23

What are the mechanisms of resistance for lincosamides (clindamycin)

Answer 23

Erm dimethylation of A2058, Adenylation, Efflux transporters expressed

Question 24

What are the two parts of streptogramin

Answer 24

Streptogramin A (Daflopristin) and Streptogramin B (Quinuprisitn)

Question 25

Where do the two streptogramins bind

Answer 25

Streptogramin A (Dafloprstin) binds near the peptidy transferase center and Streptogramin B (Quinuprisitn) binds the nascent peptide tunnel

Question 26

T/F: When only one streptogramin binds it is bacterocidial but when both binds they become bacteriostatic

Answer 26

False: Streptogramins have synergy that allows their combination to be bactericidal

Question 27

What is the mechanism of synergy for streptogramins

Answer 27

Binding of dalfopristin remodles the rRNA structure stimulating binding of quinupristin

Question 28

What are the mechanisms of resistance for streptogramins

Answer 28

Vat acetyltransferase adds acetyl group to dalfopristin, Vgb lyase opens circle for quinupristin, Erm methyltransferase dimethylates A2058

Question 29

What is the MOA of aminoglycosides

Answer 29

Aminoglycosides take the place of two nucleotides in the decoding center that conform correct codon/anticodon interactions, there is no more checking wrong amino acids are incorporated in growing protein

Question 30

What subunit do aminoglycosided bind, where on that subunit

Answer 30

small subunit, the decoding center

Question 31

What gives aminoglycosides their selectivity

Answer 31

The nucleotide 1408 of the small subunit rRNA is A while in eukaryotes it is G

Question 32

T/F: Aminoglycosides are nephrotoxic and ototoxic

Answer 32

True

Question 33

What are enzyme and enzyme functions that lead to resistance to amnioglycosides

Answer 33

ArmA/RmtA methtransferase methylates G1405 near the aminoglycoside site, NpmA rRNA methyltransferase modifies A1408

Question 34

What are changes to the drug structure of aminoglycosides that leads to resistance

Answer 34

the drug becomes N-acetylated, O-phosphorylated or O-adenylated causing steric hinderance that prevents binding to the target

Question 35

What makes streptomycin different from other aminoglycosides

Answer 35

It has the same the MOA but a different binding site

Question 36

Why are older generations of tetracyclines more reactive

Answer 36

Ring A can undergo renolization and protonization that could potentially cause it to lose half of its activity

Question 37

What is the MOA of Tetracyclines

Answer 37

Tetracycline binds where tRNA would bind not allowing the correct matchups to happen between codons and anticodons

Question 38

What subunit of the ribosome does tertracycline bind to

Answer 38

Small subunit

Question 39

What are the mechanisms of resistance against tetracylcines

Answer 39

Tet(M) or Tet(O) evict the drug from the ribosome (Ribosome protection), Tet(A) or Tet(B) remove the drug from the ribosome (efflux pumps)

Question 40

What does RNA polymerase do

Answer 40

convert DNA into messenger RNA (transcription)

Question 41

T/F: Rifampicin is an inhibitor of transcription and binds the alpha subunit

Answer 41

False: Rifampicin binds in the exit of the RNA tunnel in the Beta subunit of RNA polymerase and inhibits formation of the second or third phosphodiester bonds

Question 42

T/F: Sulfonamides are bacteriocidial and have no structural analogs

Answer 42

False: Sulfonamides are bacteriostatic antibiotics and are a structural analog to PABA

Question 43

How do sulfonamides cause less nucleotides and amino acids available to the cell

Answer 43

Sulfonamides competitively competes with PABA for Dihydropteroate synthaase causing less Folic acid and tetrahydrofolate which is a precursor to nucleotides and amino acids

Question 44

How do adding electron withdrawing groups aid in solubility and potency of the drug

Answer 44

reducing the pKA of amino group closer to what PABAs also allowing solubility at neutral pH leading to know crystalization in the kidneys

Question 45

How does trimethoprim act synergistically with sulfonamides, what enzyme

Answer 45

Trimethoprim acts upon another enzyme in the same pathway that is inhibited by sulfonamides, dihydrofolate reductase