Week 11 - Antimicrobials And Antibiotics

Question 1

What are antibiotics characteristics based on?

Answer 1

-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)

Question 2

What are essential cellular structures and processes in bacteria?

Answer 2

• cell wall
• plasma membrane
• protein synthesis

Question 3

What part of a bacteria is a target for many antibiotics and why?

Answer 3

-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

Question 4

What test can determine a bacteria’s cell wall structure and composition?

Answer 4

Gram staining test

+ve = purple
(Staphylococci, streptococci, enterococci)

-ve = pink
(E.coli, pseudomomas, salmonella)

Question 5

What do the cell walls of gram positive bacteria have?

Answer 5

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

Question 6

What is the cell wall of gram negative bacteria like?

Answer 6

• cell wall only has a think peptidoglycan layer

- explains why abx targeting peptidoglycan biosynthesis are not as effecting against gram negative bacteria

Question 7

Name the antibiotics that act on peptidoglycan biosynthesis?

Answer 7

• penicillins (B-lactam)
• cephalosporins (B-lactam)
• carbapenems (B-lactam)

-vancomycin

Question 8

What is the mechanism of action of B-lactam antibiotics?

Answer 8

• inhibit the enzymes involved in the transpeptidase cross-linking reaction
• interfere with linking individual chains together
• disrupt peptidoglycan synthesis leading to autolysis

Question 9

What cells are B-lactam antibiotics effective against?

Answer 9

Growing and dividing cells

Question 10

How are bacteria killed by B-lactam antibiotics?

Answer 10

Autolysis (bactericidal)

Question 11

What to resistant bacterial species produce against B-lactam antibiotics?

Answer 11

B-lactamase

-a secreted enzyme which inactivates abx by breaking down their B-lactam ring

Question 12

What type of antibiotics are penicillins, what are they effective in treating and what side effects may occur?

Answer 12

B-lactam abx

• penicillin (natural), aminopenicillin (amoxicillin, ampicillin)
• very effective against gram +ve
• some allergic reactions
• aminopenicillins better tolerated

Question 13

What type of antibiotics are cephalosporins and what are they effective in treating?

Answer 13

B-lactam abx

1st - cefalexin, cefazolin (treats gram +ve)

2nd - cefaclor, cefuroxime (treats anaerobes)

3rd - cefixime, cefpodoxime (treats gram -ve)

4th - cefepime (treats pseudomonas)

Question 14

What type of antibiotics are carbapenems, what are they effective in treating and how are they administered?

Answer 14

B-lactam abx

• meropenem, ertapenem, imipenem
• broad spectrum - generally effective against all but MRSA and VRE (vancomycin resistant enterococci)
• only available IV

Question 15

What type of antibiotic is vancomycin and how does vancomycin work?

Answer 15

-glycopeptide antibiotic (more allergic reactions)

• inhibitor of cell wall biosynthesis
• different mode of action to B-lactams
• different chemical structure

Question 16

What is vancomycin effective against and how is it administered?

Answer 16

• MRSA
• given IV
• however emerging cases of resistance - VRSA, VRE (vancomycin resistant enterococci)

Question 17

What does protein synthesis require?

Answer 17

rRNA-protein complexes = RIBOSOMES

No protein synthesis without ribosomes

Question 18

How do bacterial ribosomes differ compared to human ribosomes?

Answer 18

• bacterial ribosomes are smaller

- bacteria = 30S subunit and 50S subunit

Question 19

How do some antibiotics inhibit protein synthesis?

Answer 19

-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)

Question 20

What bacteria do antibiotics inhibiting protein synthesis affect?

Answer 20

• broad spectrum (both gram +ve and -ve species)

- most are bacteriostatic

Question 21

What is an issue with antibiotics inhibiting protein synthesis?

Answer 21

Associated with greater toxicity (human mitochondrial ribosomes are inhibited too)

Question 22

Which antibiotics inhibit DNA biosynthesis?

Answer 22

Fluoroquinolones

Question 23

Name some Fluoroquinolones

Answer 23

Ciprofloxacin
Norfloxacin
Levofloxacin
Moxifloxacin

Question 24

What is the mechanism of action of Fluoroquinolones?

Answer 24

-inhibit bacterial enzymes (DNA gyrase) with essential roles in DNA replication

Question 25

What bacteria do Fluoroquinolones treat?

Answer 25

• broad spectrum, synthetic
• effective against gram -ve bacteria and intracellular pathogens (legionella, mycoplasma)
• higher levels of toxicity associated with them

Question 26

What is the mechanism of action of rifampicin?

Answer 26

• inhibits bacterial but not human RNA polymerases

- so RNA biosynthesis can’t occur

Question 27

What is rifampicin used to treat?

Answer 27

Used predominantly for treating tuberculosis

Question 28

What can bacteria but not humans make?

Answer 28

Folic acid (Vit B9)

Question 29

What does folic acid contribute to in bacterial cells?

Answer 29

Nucleotides biosynthesis

Question 30

Which antibiotics are folate biosynthesis inhibitors?

Answer 30

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

Question 31

What are the characteristics of antibiotics and what is affected by them?

Answer 31

-kill bacteria (bactericidal)

Range of bacterial species affected:

• large number = broad spectrum
• limited number = narrow spectrum
• single species = limited spectrum