Targeting Pathogenic Organisms: Bacteria

Question 1

What are the 5 antibiotic targets and one example for each?

Answer 1

1) Cell wall - Beta lactam Abx
2) Cell membrane - Polymyxins
3) DNA/RNA synthesis - Fluoroquinolones
4) Protein synthesis - Tetracyclines
5) Folate synthesis - Trimethoprim

Question 2

What are the 2 types of bacteria

Answer 2

Gram negative and gram positive.
-Gram positive - purple - thick peptidoglycan cell wall: they retain the dye.
-Gram negative - dont retain the dye - have an inner and outer membrane with the peptidoglycan layer in between (periplasmic space)

Question 3

Beta lactam abx structure

Answer 3

4 membered cyclic amide.

Question 4

Process of cell wall synthesis

Answer 4

The terminal D-alanine residues of glycan strands are removed by PBP/transpeptidase enzymes -> allows cross linkage of glycan chains.

Question 5

MOA of beta lactam ABX

Answer 5

Beta lactam Abx inhibit the active site of the PBP so the D-alanine residue is not removed so there is no cross linkage of glycan chains.

Question 6

Resistance of beta lactam ABX

Answer 6

Bacteria can produce the beta lactamase enzyme which degrades the beta lactam ring.

Question 7

How to overcome beta lactamase resistance

Answer 7

Addition of an isoxazole ring such as in flucloxacillin which acts as a steric shield against the beta lacta

Question 8

What is the consequence of bactericidal drugs on slow-growing bacteria?

Answer 8

Longer treatment time required. Dose might need adjusting with a longer course of antibiotics.

Question 9

Vancomycin MOA

Answer 9

Inhibits cell wall synthesis. Forms hydrogen bonds with the terminal D-alanyl-D-alanine moieties preventing action by PBP.

Question 10

Polymyxin structure

Answer 10

Heptapeptide ring and an exocyclic chain with a fatty acid tail.

Question 11

MOA polymyxin

Answer 11

The heptapeptide ring of polymyxin binds to LPS and displaces Ca and Mg ions that are holding the LPS in place. Also, the fatty acid tail interacts with LPS and allows insertion of polymyxin into the membrane -> forms cracks. detergent mode of action.

Question 12

Gram negative or positive polymyxin

Answer 12

Gram negative as only negative have LPS in cell membrane.

Question 13

The spectrum of polymyxin is limited to

Answer 13

serious aerobic gram negative infections because of polymyxin side effects

Question 14

Polymyxin SE

Answer 14

Nephrotoxicity is a major SE.
Also needs to be given by injection as not absorbed well orally.

Question 15

What is a major component of gram negative cell membrane

Answer 15

LPS

Question 16

Tetracycline MOA

Answer 16

Binds to the 30S subunit of bacterial ribosomes and prevents tRNA from building polypeptide chain

Question 17

Tetracycline contraindications

Answer 17

Pregnancy and children. It binds to calcium ions and oxidise on light exposure causing permanent teeth staining and impaired bone formation.

Question 18

Ribosomal subunit in bacteria

Answer 18

Humans: 60S and 40S.
Bacteria: 50S and 30S

Question 19

Protein transcription and translation

Answer 19

1. Transcription: the process of making messenger RNA (mRNA), a temporary copy of a gene’s DNA sequence.
2. Translation: in the ribosome the mRNA is used to direct the synthesis of a protein’s sequence of amino acids. a) A ribosome brings together the mRNA, and the tRNA; b) tRNA molecules carry amino acids used to synthesise the protein chain.

Question 20

Importance of folate for bacteria

Answer 20

Bacteria use folic acid in order to synthesize the nucleic acids that make up their DNA.

Question 21

What is the folate synthesis pathway?

Answer 21

PABA -> dihydropterolatic acid by dihydropterolatic synthetase - > dihydrofolatic acid by glutamate -> tetrahydrofolate by dihydrofolate reductase.

Question 22

Trimethoprim MOA

Answer 22

Analogue of dihydrofolatic acid by inhibiting the dihydrofolate reductase enzyme preventing formation of tetrahydrofolate.

Question 23

Cytochrome P450 enzyme is responsible for the metabolism of hundreds of drugs. The P450 enzyme CYP2C8 is inhibited by trimethoprim. What do you think would happen to drugs that are normally metabolised by CYP2C8 (such as warfarin) if given alongside Trimethoprim?

Answer 23

Causes toxicity due to high levels of warfarin accumulating. Decreased metabolism. Increases the effect of warfarin.

Question 24

MOA Sulfonamide

Answer 24

Inhibits folate synthesis by acting as an analogue of PABA inhibits the dihydropterolate synthetase enzyme.

Question 25

How is DNA synthesis carried out in bacteria and what is the role of a key enzyme in this pathway

Answer 25

During dna synthesis, the DNA is unwound to allow for complementary base pairing to occur.

DNA gyrase is responsible for this.

Question 26

Structure of DNA gyrase

Answer 26

2 subunits: gyr A and gyr B.

gyr A = breakage, passage and assembly of rejoining DNA.

Question 27

MOA fluroquinolones

Answer 27

Ends in ‘floxacin’ suffix.

Bind to and inhibit the gyrA subunit preventing DNA synthesis

Question 28

MOA rifampicin

Answer 28

inhibits DNA-dependent RNA polymerase

Question 29

Who is antibiotic prophylaxis limited to and why?

Answer 29

limited to at risk groups, recurrent infections and high risk procedures such as: immunocompromised, loss of spleen, gastrointestinal surgeries and cardiac procedures.

Due to resistance.

Question 30

What 3 scenarios is antibiotic prophylaxis considered for?

Answer 30

Primary/prevention of initial infection
Secondary/prevention of recurrent infection
Elimination of a colonising organism

Question 31

Are vaccines effective against bacteria?

Answer 31

Yes.

Question 32

how do vaccines work?

Answer 32

Vaccinations work by eliciting an immune response from the host and generally contain a component of the infectious organism such as: Live/attenuated/inactivated organisms; Toxoid; Polysaccharide.

Question 33

MOA Mupirocin/Bactroban

Answer 33

Prophylactic of MRSA.
Binds and Inhibits the isoleucyl transfer-RNA enzyme