Lecture 23 -- Cell Wall and Protein Inhibition

Question 1

What is the difference between antibiotics and antimicrobials

Answer 1

antibiotics – natural, more complex

antimicrobials – man-made, simple structures

Question 2

What are the three classes of antimicrobials?

Answer 2

• sulfadrugs
• quinolones
• oxazolidinone

Question 3

Name the 4 clinically validated targets for antibiotics in bacteria

Answer 3

• inhibition of protein synthesis
• inhibition of DNA/RNA synthesis
• inhibition of cell wall synthesis
• inhibition of folate synthesis

Question 4

what are the three phases of PG synthesis and what occurs in each phase

Answer 4

cytoplasmic (assembly of monomer units --> Park's nucleotide, lipid I, lipid II)
membrane associated (transport to site of polymerization --> lipid cycle)
extra cytoplasmic (polymerization --> peptidoglycan)

Question 5

Which PG inhibiting antibiotic inhibits MurA by blocking the active site?

Answer 5

Fosfomycin

Question 6

Which PG inhibiting antibiotic acts as a competitive inhibitor for D-ala

Answer 6

D-cycloserine

Question 7

Which two enzymes does D-cycloserine inhibit

Answer 7

the racemase and the Ddl (d-ala-d-ala ligase)

Question 8

the transfer of park’s nucleotide to undecaprenyl phosphate, generating lipid I is accomplished through what

Answer 8

MraY/translocase I

Question 9

What enzyme do nucleoside antibiotics inhibit by competing with park’s nucleotide for its active site

Answer 9

MraY/translocase I

Question 10

What PG inhibiting antibiotic inhibits the cycle of lipid II being flipped across the membrane and the recycling of undecaprenyl phosphate

works by binding the substrate rather than the enzyme

Answer 10

Bacitracin

Question 11

Which is involved in crosslinking: transpeptidase or transglycosylate?

Answer 11

transpeptidase

Question 12

Which is involved in the linking of PG subunits: transpeptidase or transglycosylase?

Answer 12

transglycosylase

Question 13

Which antibiotic targets transglycosylation and is used as a growth promoter in animal feed?

Answer 13

Moenomycin

Question 14

Which antibiotics target transpeptidation, are glycopeptides, do not penetrate Gram-negative outer membranes, and bind to pentapeptide tails/D-Ala-D-Ala in PG

Answer 14

Vancomycin and Teichoplanin

Question 15

Which antibiotics are synthetic compounds that are structural analogs of D-Ala-D-Ala, blocking transpeptidation by irreversibly binding to transpeptidase

Answer 15

Beta-lactams

Question 16

what amino acid is in the active site of a transpeptidase that acts as a nucleophile for beta-lactams

Answer 16

serine

Question 17

what are the two hypothetical beta-lactam killing mechanisms and what do they result in

Answer 17

non-lytic mechanism; cell death

lytic mechanism; signal for cell lysis

Question 18

List the structures of a bacterial ribosome

Answer 18

• small 30s subunit (20 proteins)
• large 50s subunit (30 proteins)
• 2 RNA mcs within large subunit –> 23S and 5S

Question 19

List the three steps of protein synthesis

Answer 19

Initiation (binding and initial loading), Elongation (continual loading and peptidyl transferase reactions), Exit/termination (hydrolysis of polypeptide and deconstruction of ribosome)

Question 20

Which antibiotics are characterized by a lactone containing ring, are bacteriostatic, and whose sugar interactions determine binding and specificity

Answer 20

macrolides

Question 21

which antibiotic has a mechanism of action where it acts as a plug, binding to the 23S section of the ribosome, physically interacting with the peptide chain, allowing the formation of only short peptides as well as the assembly of the 50S subunit

Answer 21

macrolides

Question 22

Which type of antibiotics bind to the 30S ribosomal subunit without interacting with the protein, preventing the binding of aminoacyl-tRNA which is prematurely released, is largely bacteriostatic

Answer 22

tetracycline

Question 23

what antibiotics are bacteriocidal at high concentrations, work against gram negatives (not gram positives), are hydrophilic sugars with multiple amino groups

Answer 23

Aminoglycoside