The Biochemistry Of Antibiotics; From Serendipity To Targeted Discovery Flashcards
What’s bacteriocidal?
Antibiotics that kill bacteria
Example of bacteriocidal?
Penicillins
What’s bacteriostatic?
Antibiotics that block growth
Examples of bacteriostatic antibiotics?
Tetracyclines
Sulphonamides
Who first discovered penicillin?
Ernest Duchesne (French med student) in 1896
First true antibiotic?
Penicillin
Who rediscovered penicillin?
Alexander Fleming in 1928
Where did Alexander Fleming discover penicillin?
Clarence memorial wing, st Mary’s hospital, London
Where did the fungus come from?
Freeman’s lab
What was Florey’s experiment?
To determine how much penicillin is needed to destroy E.coli in mice
Method of Florey’s experiment?
- Injected peritoneal injection of e.coli 1 day prior to treatment
- 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)
Who isolated penicillin notatum?
Fleming
What was penicillin most effective for during the war?
Treating staphyloccus
Following the war, was penicillin effective in treating?
Rheumatic fever and syphilis
What is used in the production of cheese and various meats?
Several species of penicillium
What are the 5 main targets of antibiotic action?
- Inhibition of cell wall synthesis (eg penicillin)
- Inhibition of protein synthesis
- Inhibition of DNA or RNA synthesis
- Inhibition of folate synthesis
- Membrane disruption
What does penicillin do and who discovered it?
Inhibits the bacterial cell wall synthesis- discovered by Joshua lederberg (Nobel prize 1958)
Essentially, what happens in penicillin?
Cytoplasm escapes as no cell wall
What is a primary component of the bacterial cell wall?
Peptidoglycan (provides support and rigidity)
What enzyme forms the cell wall- through cross linking peptidoglycans?
DD-transpeptide (also called a penicillin binding protein)
What is penicillin similar to?
D-Ala-D-Ala
Example of inhibition of protein synthesis?
Aminoglycosides
What do antibiotics do in inhibition of protein synthesis?
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
Example of inhibition of DNA or RNA synthesis?
Rifamycin class of antibiotics (these antibiotics bind to actively transcribing RNA polymerase enzyme
Example of the inhibition of folate synthesis (antimetabolites)?
Sulfonamides competitively inhibit dihydropteroate synthetase (an enzyme that converts P-aminobenzoic acid (PABA) into folic acid
What is the most widespread target of clinical utility in antibiotics?
Membrane disruption
Example of antibiotic membrane disruption?
Lipopeptide antibiotics (eg daptomycin)
What happens with daptomycin?
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)
