Week 11 - Antimicrobials And Antibiotics Flashcards
What are antibiotics characteristics based on?
-target/mode of action
- antibiotics interfere with-inhibit essential cellular structures/processes
- antibiotics target bacteria-specific structures/processes
-such modes of action make them - toxic to bacteria only and innocuous to humans (little/no side effects)
What are essential cellular structures and processes in bacteria?
- cell wall
- plasma membrane
- protein synthesis
What part of a bacteria is a target for many antibiotics and why?
-cell wall
- responsible for cell integrity, protects bacteria from toxic substances
- absence of functional cell wall = death by autolysis
Human cells don’t have cell walls
-bacteria specific organelle
What test can determine a bacteria’s cell wall structure and composition?
Gram staining test
+ve = purple
(Staphylococci, streptococci, enterococci)
-ve = pink
(E.coli, pseudomomas, salmonella)
What do the cell walls of gram positive bacteria have?
Thick layers of peptidoglycan chains
- 40 chains linked together
- each chain is built up of covalently linked sugars
- short chains are attached to NAM (N-acetylmuramic acid)
- peptidoglycan chains cross-link via peptidyl bridges (catalysed by specific enzymes)
-these enzymes and the reactions they catalyse, are targets of antibiotics
What is the cell wall of gram negative bacteria like?
- cell wall only has a think peptidoglycan layer
- explains why abx targeting peptidoglycan biosynthesis are not as effecting against gram negative bacteria
Name the antibiotics that act on peptidoglycan biosynthesis?
- penicillins (B-lactam)
- cephalosporins (B-lactam)
- carbapenems (B-lactam)
-vancomycin
What is the mechanism of action of B-lactam antibiotics?
- inhibit the enzymes involved in the transpeptidase cross-linking reaction
- interfere with linking individual chains together
- disrupt peptidoglycan synthesis leading to autolysis
What cells are B-lactam antibiotics effective against?
Growing and dividing cells
How are bacteria killed by B-lactam antibiotics?
Autolysis (bactericidal)
What to resistant bacterial species produce against B-lactam antibiotics?
B-lactamase
-a secreted enzyme which inactivates abx by breaking down their B-lactam ring
What type of antibiotics are penicillins, what are they effective in treating and what side effects may occur?
B-lactam abx
- penicillin (natural), aminopenicillin (amoxicillin, ampicillin)
- very effective against gram +ve
- some allergic reactions
- aminopenicillins better tolerated
What type of antibiotics are cephalosporins and what are they effective in treating?
B-lactam abx
1st - cefalexin, cefazolin (treats gram +ve)
2nd - cefaclor, cefuroxime (treats anaerobes)
3rd - cefixime, cefpodoxime (treats gram -ve)
4th - cefepime (treats pseudomonas)
What type of antibiotics are carbapenems, what are they effective in treating and how are they administered?
B-lactam abx
- meropenem, ertapenem, imipenem
- broad spectrum - generally effective against all but MRSA and VRE (vancomycin resistant enterococci)
- only available IV
What type of antibiotic is vancomycin and how does vancomycin work?
-glycopeptide antibiotic (more allergic reactions)
- inhibitor of cell wall biosynthesis
- different mode of action to B-lactams
- different chemical structure
What is vancomycin effective against and how is it administered?
- MRSA
- given IV
- however emerging cases of resistance - VRSA, VRE (vancomycin resistant enterococci)
What does protein synthesis require?
rRNA-protein complexes = RIBOSOMES
No protein synthesis without ribosomes
How do bacterial ribosomes differ compared to human ribosomes?
- bacterial ribosomes are smaller
- bacteria = 30S subunit and 50S subunit
How do some antibiotics inhibit protein synthesis?
-some bind to and inhibit protein components of the 30S subunit of the ribosomes
(tetracycline, aminoglycosides - gentamycin, streptomycin)
-others bind to and inhibit protein components of the 50S subunit
(Chloramphenicol, Macrolides - erythromycin)
What bacteria do antibiotics inhibiting protein synthesis affect?
- broad spectrum (both gram +ve and -ve species)
- most are bacteriostatic
What is an issue with antibiotics inhibiting protein synthesis?
Associated with greater toxicity (human mitochondrial ribosomes are inhibited too)
Which antibiotics inhibit DNA biosynthesis?
Fluoroquinolones
Name some Fluoroquinolones
Ciprofloxacin
Norfloxacin
Levofloxacin
Moxifloxacin
What is the mechanism of action of Fluoroquinolones?
-inhibit bacterial enzymes (DNA gyrase) with essential roles in DNA replication
What bacteria do Fluoroquinolones treat?
- broad spectrum, synthetic
- effective against gram -ve bacteria and intracellular pathogens (legionella, mycoplasma)
- higher levels of toxicity associated with them
What is the mechanism of action of rifampicin?
- inhibits bacterial but not human RNA polymerases
- so RNA biosynthesis can’t occur
What is rifampicin used to treat?
Used predominantly for treating tuberculosis
What can bacteria but not humans make?
Folic acid (Vit B9)
What does folic acid contribute to in bacterial cells?
Nucleotides biosynthesis
Which antibiotics are folate biosynthesis inhibitors?
Sulfonamides (analogues of PABA, act by substrate competition)
Trimethoprim (inhibits dihydrofolate reductase)
Co-trimoxazole (a mixture of both 5:1, inhibits both enzymes)
ALL PREVENT BIOSYNTHESIS OF NUCLEOTIDES
What are the characteristics of antibiotics and what is affected by them?
-kill bacteria (bactericidal)
Range of bacterial species affected:
- large number = broad spectrum
- limited number = narrow spectrum
- single species = limited spectrum
