Antimicrobial Chemotherapy

Question 1

Which are the chemotherapy agents target features found in microbes?

Answer 1

Ribosome, cell wall (PG), nucleic acid synthesis, cell membrane

Question 2

What are the types of antimicrobial agents?

Answer 2

Antibiotic drugs (penicillin)
Antiseptics (benzalkonium chloride)
Disinfectants (hypochlorite bleaches)

Question 3

Name the two types of antimicrobial drugs

Answer 3

Bactericidal -> kill infecting bacteria
Bacteriostatic -> halt growth (immune system continues)

Question 4

What are narrow spectrum and broad spectrum antimicrobial drugs?

Answer 4

NS: against limited subset of bacteria
BS: against wide range of bacteria

Question 5

What are the two types of chemotherapeutic drugs?

Answer 5

Synthetic drugs (sulphonamides) -> lab synthesized
Antibiotics (penicilllin) -> natural products

Question 6

What are the types of inhibitors (antibiotic classes)

Answer 6

Inhibitors of cell wall biosynthesis
Disruptors of membrane function
Inhibitors of nucleic acid synthesis
Inhibitors of protein synthesis
Inhibitors of metabolism

Question 7

What type of inhibitor are beta-lactams?

Answer 7

Cell wall biosynthesis inhibitor

Question 8

True or false: penicillin attacks transglycosylase

Answer 8

False: penicillin attacks transpeptidase

Question 9

What is the mechanism of inhibition of beta-lactams?

Answer 9

Target cell wall biosynthesis (transpep.)
inhibit NAM NAG crosslinking

Question 10

Explain glycopeptides

Answer 10

Prevent NAM-NAG to be in mesh
Targets substrates not enzymes
Unable to penetrate OM of g.-

Question 11

What do the two types of vancomycins do?

Answer 11

A: Uncrosslinked strands of pre-existing PG
B: Lipid II substrate before polymerisation into PG

Question 12

True or false: Vancomycin can act on g.+ and g. -

Answer 12

False: Vancomycin can only act on g.+

Question 13

True or false: beta-lactams can act only on g.-

Answer 13

False: beta-lactams can act on g.- and g.+

Question 14

Explain colistin’s (polymyxins) disruption of membrane function

Answer 14

Target LPS in g.- (destabilises LPS)
Not absorbed by GI so must be topical or IV

Question 15

What type of inhibitor is Rifampicin?

Answer 15

Nucleic acid (transcription) inhibitor

Question 16

What does Rifampcin do?

Answer 16

RNA pol. inhibitor
Blocks transcription elongation (initiation)

Question 17

What type of inhibitor are Quinolones?

Answer 17

DNA gyrase inhibitors

Question 18

What are two types of Quinolones?

Answer 18

Nalidixic acid (g.-)
Ciprofloxacin (broad)

Question 19

True or false: Drugs have high binding affinity for 70S with low affinity for 80S

Answer 19

True

Question 20

What type of inhibitors are aminoglycosides?

Answer 20

Protein synthesis inhibitors

Question 21

What does Streptomycin (aminoglycoside) do?

Answer 21

High affinity to 16S rRNA of 30S
Inhibit formation of ribosomal initiation

Question 22

What do tetracyclines (aminoglycoside) do?

Answer 22

Bind to 16S rRNA of 30S subunit and block A-site in 70S ribosome

Question 23

What do macrolides (aminoglycoside) do?

Answer 23

Inhibit 50S subunit
Blocks elongating peptide exit tunnel

Question 24

How does one determine mechanism of action?

Answer 24

Seeing what drug is binding to (biochemical ligand binding assay)
Whole genome sequencing
If it is inhibiting ribosome or inhibiting cell wall

Question 25

What are the types of resistance mechanism?

Answer 25

Keep antibiotic outside cell Modify/mutate molecular target of antibiotic Destroy/inactivate antibiotic

Question 26

Describe the destroy/deactivate antibiotic resistance mechanism

Answer 26

Modify/destroy antibiotic with offensive enzymes

Question 27

Describe the modify/mutate molecular targe of antibiotic resistance mechanism

Answer 27

Change structure of ribosomes for ribosome inhibitors so they can't be bound

Question 28

What are beta-lactamase enzymes?

Answer 28

Hydrolytic enzymes that destroy beta-lactam antibiotics

Question 29

From what did beta-lactamase evolve from?

Answer 29

PBP (transpeptidases)

Question 30

In what ways are beta-lactamase and PBP's similar?

Answer 30

Amino acid sequence similarities -> transpeptidase similar Gene duplication + mutational remodeling

Question 31

What are the types of spread of AMR genes?

Answer 31

Transformation (free DNA) Transduction (bacteriophage) Conjugative transfer (plasmid/transposon)

Question 32

How does antibiotic resistance spread?

Answer 32

Spread HGT of pre-existing resistance genes in situ evolution of new resistance genes

Question 33

Describes Kirby-Bauer disc diffusion assay

Answer 33

Growth inhibited until Minimum Inhibitory Concentration (MIC) Use of Mast rings

Question 34

Why is keeping PABA free medium important?

Answer 34

For microbial growth Antibiotic diffuses (3D)

Question 35

What is a clinically susceptible organism?

Answer 35

High likelyhood of therapeutic success

Question 36

What does MIC determine?

Answer 36

Whether a given strain is susceptible or resistant to antibiotic

Question 37

What is MBC?

Answer 37

Minimum bactericidal concentration Lowest concentration of antimicrobial that will kill test organism