lecture 9

Question 1

state different classes of beta lactam antibiotics and why they are

Answer 1

penicillin, cephalosporin, cephamycin, carbapenem, monobactam, clavam. they all have a beta lactam ring

Question 2

how do beta lactam antibiotics work

Answer 2

mimic d-ala-d-ala dipeptide involved in the cross linking of peptidoglycan. beta lactam ring is highly strained. beta lactam antibiotics behave as a substrate mimic for penicillin binding proteins and undergoes an acyl-substitution reaction with an active site nucleophile which forms a stable acyl-enzyme complex.
the enzyme containing acyl-intermediate in inactive, resulting in bacterial lysis

Question 3

how can beta lactam antiobiotics resistance happen?

Answer 3

target modification, amidases(removes penicillin side chain), beta-lactamases

Question 4

how does beta-lactamases work

Answer 4

answer in slide 7

Question 5

origin of beta-lactamases

Answer 5

probably came from pbps. use of antibiotics pressured bacteria to produce beta-lactamase. the genes can be encoded dor by bacterial chromosomes or more commonly plasmids. the plasmids can be transfected inter, and intra- species

Question 6

types of beta- lactamases

Answer 6

Class A – penicillinases e.g., TEM-1 and -2.
Class B – metallo-β-lactamases e.g. ,NDM-1.
Class C – ‘Cephalosporinases’.
Class D – ‘Extended spectrum β-lactamases’, hydrolysing β-lactam antibiotics with more variable structures.

Question 7

give a strategy for overcoming beta- lactamases and its pros and cons

Answer 7

Develop new antibiotics which are resistant to hydrolysis by β-lactamases.
This has been done extensively and can be very successful but
Resistance can quickly develop to new antibiotics (especially in hospitals where intensive use occurs).
The number of truly new antibiotics still to be discovered is very limited (most have already been discovered > 30 years ago).
Patients often fail to take the full course due to feeling better after a few days – often exacerbates the problem of resistance.
Careful use of antibiotics is required (Pharmacist role in patient education).

Question 8

how new antibiotics are discovered

Answer 8

Natural product screening programmes:
Requires screening of bacterial/fungal/other natural product mixtures or libraries of compounds against infective organism.
Most antibiotics already discovered.
Manipulation of biosynthetic pathways to make ‘semi-synthetic’ antibiotics:
Often involves changing the penicillin side-chain (and other parts of other β-lactam antibiotics).
Engineering of biosynthetic pathways using genetic techniques