micro lecture 3

Question 1

what is the essential core of β-lactam antibiotics

Answer 1

β-lactam ring.

Question 2

how do β-lactam work as an antibiotic?

Answer 2

Bind and inhibit PBPs (note: PBP subtypes exist)
β-lactam ring resembles D-alanyl-D-alanine portion of peptide side chains
Transpeptidase (PBP) irreversibly binds with lactam and not side chain
Disruption of peptidoglycan crosslinking
(generally considered bactericidal - lysis)

Question 3

Lactam = _______+________

Answer 3

lactone + amide

Question 4

what is lactone?

Answer 4

cyclic carboxylic ester

Question 5

list types of β-lactams - resistance

Answer 5

Intrinsic resistance

Acquired resistance

Question 6

explain “Intrinsic resistance” as a type of β-lactams - resistance

Answer 6

Resistance is intrinsic to structure or function of bacterial species
(do they have a typical crosslinked cell wall, is it accessible and is your lactam a good match for this precise PBP?)

Question 7

explain “Acquired resistance” as a type of β-lactams - resistance

Answer 7

A previously sensitive bacterium acquires a mutation or obtains new genetic material allowing it to resist activity of the agent

Question 8

describe the two different mechanism of enzymatic inactivation of β-lactam antibiotics?

Answer 8

beta lactamases catalyse the hydrolytic cleavage of beta lactam rings:

1. serine-beta-lactamases form a transient enzyme antibiotic intermediate, which is quickly hydrolysed
2. metallo-beta-lactamases utilize a bound zinc ion to activate water for a hydrolytic attack on the beta-lactam ring

Question 9

list facts about natural penicillin

Answer 9

Relatively hydrophobic side chain

Majority of bacteria either intrinsically resistant or have acquired resistance

Susceptible to many β-lactamases

Question 10

list 4 types or subgroups of penicillin

Answer 10

Natural penicillin
Antistaphylococcal penicillins
Aminopenicillins
Extended-spectrum penicillins

Question 11

why cant penicillin G be given orally?

Answer 11

because the amide group present in its structure would be broken by the stomach acid

Question 12

why is Penicillin V okay to be given orally even though it is like penicillin G?

Answer 12

because the ether bond present which is basic can neutralize the acidic ph of the stomach

Question 13

why is flucloxacillin stable to Staphylococcal lactamase

Answer 13

because it has a large R1 group or side chain which reduced binding by staphylococcal lactamases

Question 14

why is amoxicillin more water soluble and how does that help?

Answer 14

it is water soluble because of the alcohol and amine group attached to it and also it is important to be water soluble so as to cross gram negative outer membrane

Question 15

how does Piperacillin blocks some

G- lactamases.

Answer 15

because it has V Large and

“electron-heavy” R1 group increases water solubility and blocks some G- lactamases, increasing G-spectrum

Question 16

list facts about Natural penicillin

Answer 16

Relatively hydrophobic side chain

Majority of bacteria either intrinsically resistant or have acquired resistance

Susceptible to many β-lactamases

Question 17

list types of Natural penicillin

Answer 17

Penicillin G, Penicillin V

Question 18

list facts about Antistaphylococcal penicillins

Answer 18

Bulky side chains: reduced binding by staphylcoccal lactamases

MRSA / MRSE have different PBPs (mecA gene / PBP2)

Bulky, relatively hydrophobic side chains prevent penetration through porins (v poor G- action)

Question 19

list facts about Aminopenicillins

Answer 19

Additional amino group on side chains increases hydrophilicity

Pass better through porins

Extends spectrum of G– activity

Question 20

list facts about Extended-spectrum penicillin

Answer 20

Side chains enhance porin penetration

More resistant to G- lactamases

Often less active against G+ organisms

Question 21

list examples of Anti-staphylococcal penicillin

Answer 21

flucloxacillin, methicillin

Question 22

list examples of Aminopenicillins

Answer 22

amoxicillin, ampicillin

Question 23

list examples of Extended-spectrum penicillin

Answer 23

piperacillin, ticarcillin

Question 24

what is meant by penicillin augmentation

Answer 24

Penicillin / β-lactamase inhibitor combinations

Question 25

list two penicillin augmentations. (and resulting drug)

Answer 25

amoxicillin-clavulanate (augmentin)

piperacillin-tazobactam (tazocin)

Question 26

there is a decoy beta-lactam in penicillin augmentation true or false?

Answer 26

true

Question 27

how does β-lactamase inhibitors work?

Answer 27

Reactive molecule with high tendency to bind to β-lactamases
Thus, active antibiotic doesn’t get cleaved
Increased activity against G+ / G- / anaerobes

Question 28

list three β-lactamase inhibitors

Answer 28

clavulanate, sulbactam, tazobactam.