Targeting Pathogenic Organisms: Bacteria Flashcards
What are the 5 antibiotic targets and one example for each?
1) Cell wall - Beta lactam Abx
2) Cell membrane - Polymyxins
3) DNA/RNA synthesis - Fluoroquinolones
4) Protein synthesis - Tetracyclines
5) Folate synthesis - Trimethoprim
What are the 2 types of bacteria
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)
Beta lactam abx structure
4 membered cyclic amide.
Process of cell wall synthesis
The terminal D-alanine residues of glycan strands are removed by PBP/transpeptidase enzymes -> allows cross linkage of glycan chains.
MOA of beta lactam ABX
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.
Resistance of beta lactam ABX
Bacteria can produce the beta lactamase enzyme which degrades the beta lactam ring.
How to overcome beta lactamase resistance
Addition of an isoxazole ring such as in flucloxacillin which acts as a steric shield against the beta lacta
What is the consequence of bactericidal drugs on slow-growing bacteria?
Longer treatment time required. Dose might need adjusting with a longer course of antibiotics.
Vancomycin MOA
Inhibits cell wall synthesis. Forms hydrogen bonds with the terminal D-alanyl-D-alanine moieties preventing action by PBP.
Polymyxin structure
Heptapeptide ring and an exocyclic chain with a fatty acid tail.
MOA polymyxin
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.
Gram negative or positive polymyxin
Gram negative as only negative have LPS in cell membrane.
The spectrum of polymyxin is limited to
serious aerobic gram negative infections because of polymyxin side effects
Polymyxin SE
Nephrotoxicity is a major SE.
Also needs to be given by injection as not absorbed well orally.
What is a major component of gram negative cell membrane
LPS
Tetracycline MOA
Binds to the 30S subunit of bacterial ribosomes and prevents tRNA from building polypeptide chain
Tetracycline contraindications
Pregnancy and children. It binds to calcium ions and oxidise on light exposure causing permanent teeth staining and impaired bone formation.
Ribosomal subunit in bacteria
Humans: 60S and 40S.
Bacteria: 50S and 30S
Protein transcription and translation
- Transcription: the process of making messenger RNA (mRNA), a temporary copy of a gene’s DNA sequence.
- 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.
Importance of folate for bacteria
Bacteria use folic acid in order to synthesize the nucleic acids that make up their DNA.
What is the folate synthesis pathway?
PABA -> dihydropterolatic acid by dihydropterolatic synthetase - > dihydrofolatic acid by glutamate -> tetrahydrofolate by dihydrofolate reductase.
Trimethoprim MOA
Analogue of dihydrofolatic acid by inhibiting the dihydrofolate reductase enzyme preventing formation of tetrahydrofolate.
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?
Causes toxicity due to high levels of warfarin accumulating. Decreased metabolism. Increases the effect of warfarin.
MOA Sulfonamide
Inhibits folate synthesis by acting as an analogue of PABA inhibits the dihydropterolate synthetase enzyme.
How is DNA synthesis carried out in bacteria and what is the role of a key enzyme in this pathway
During dna synthesis, the DNA is unwound to allow for complementary base pairing to occur.
DNA gyrase is responsible for this.
Structure of DNA gyrase
2 subunits: gyr A and gyr B.
gyr A = breakage, passage and assembly of rejoining DNA.
MOA fluroquinolones
Ends in ‘floxacin’ suffix.
Bind to and inhibit the gyrA subunit preventing DNA synthesis
MOA rifampicin
inhibits DNA-dependent RNA polymerase
Who is antibiotic prophylaxis limited to and why?
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.
What 3 scenarios is antibiotic prophylaxis considered for?
Primary/prevention of initial infection
Secondary/prevention of recurrent infection
Elimination of a colonising organism
Are vaccines effective against bacteria?
Yes.
how do vaccines work?
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.
MOA Mupirocin/Bactroban
Prophylactic of MRSA.
Binds and Inhibits the isoleucyl transfer-RNA enzyme
