The Biochemistry Of Antibiotics; From Serendipity To Targeted Discovery

Question 1

What’s bacteriocidal?

Answer 1

Antibiotics that kill bacteria

Question 2

Example of bacteriocidal?

Answer 2

Penicillins

Question 3

What’s bacteriostatic?

Answer 3

Antibiotics that block growth

Question 4

Examples of bacteriostatic antibiotics?

Answer 4

Tetracyclines

Sulphonamides

Question 5

Who first discovered penicillin?

Answer 5

Ernest Duchesne (French med student) in 1896

Question 6

First true antibiotic?

Answer 6

Penicillin

Question 7

Who rediscovered penicillin?

Answer 7

Alexander Fleming in 1928

Question 8

Where did Alexander Fleming discover penicillin?

Answer 8

Clarence memorial wing, st Mary’s hospital, London

Question 9

Where did the fungus come from?

Answer 9

Freeman’s lab

Question 10

What was Florey’s experiment?

Answer 10

To determine how much penicillin is needed to destroy E.coli in mice

Question 11

Method of Florey’s experiment?

Answer 11

1. Injected peritoneal injection of e.coli 1 day prior to treatment
2. 8 hourly injections of penicillin for first 36 hrs, then longer intervals (first few hours, mice sick), as experiment progressed, health improved (4 day treatment- 21/24 mice survived)

Question 12

Who isolated penicillin notatum?

Answer 12

Fleming

Question 13

What was penicillin most effective for during the war?

Answer 13

Treating staphyloccus

Question 14

Following the war, was penicillin effective in treating?

Answer 14

Rheumatic fever and syphilis

Question 15

What is used in the production of cheese and various meats?

Answer 15

Several species of penicillium

Question 16

What are the 5 main targets of antibiotic action?

Answer 16

1. Inhibition of cell wall synthesis (eg penicillin)
2. Inhibition of protein synthesis
3. Inhibition of DNA or RNA synthesis
4. Inhibition of folate synthesis
5. Membrane disruption

Question 17

What does penicillin do and who discovered it?

Answer 17

Inhibits the bacterial cell wall synthesis- discovered by Joshua lederberg (Nobel prize 1958)

Question 18

Essentially, what happens in penicillin?

Answer 18

Cytoplasm escapes as no cell wall

Question 19

What is a primary component of the bacterial cell wall?

Answer 19

Peptidoglycan (provides support and rigidity)

Question 20

What enzyme forms the cell wall- through cross linking peptidoglycans?

Answer 20

DD-transpeptide (also called a penicillin binding protein)

Question 21

What is penicillin similar to?

Answer 21

D-Ala-D-Ala

Question 22

Example of inhibition of protein synthesis?

Answer 22

Aminoglycosides

Question 23

What do antibiotics do in inhibition of protein synthesis?

Answer 23

Bind to bacterial RNA, disrupt ribosomal structure leading to mistranslated proteins that can misfold leading to cell death- incorporation of misgolded membrane proteins into cell envelope can lead to increased drug uptake

Question 24

Example of inhibition of DNA or RNA synthesis?

Answer 24

Rifamycin class of antibiotics (these antibiotics bind to actively transcribing RNA polymerase enzyme

Question 25

Example of the inhibition of folate synthesis (antimetabolites)?

Answer 25

Sulfonamides competitively inhibit dihydropteroate synthetase (an enzyme that converts P-aminobenzoic acid (PABA) into folic acid

Question 26

What is the most widespread target of clinical utility in antibiotics?

Answer 26

Membrane disruption

Question 27

Example of antibiotic membrane disruption?

Answer 27

Lipopeptide antibiotics (eg daptomycin)

Question 28

What happens with daptomycin?

Answer 28

It’s a peptide sequence to which a fatty acid moiety is covalently attached (unclear mechanism of action- likely to include membrane disruption and loss of membrane potential)