Define Antibiotic
A substance produced by a micro-organism (or a similar substance produced wholly or partly by chemical synthesis) which at low concentrations kills or inhibits the growth of other micro-organisms
How are Antibiotics normally taken?
Used Systemically, meaning inside the body
Define Selective Toxicity
Affects only the microbe
Affects the microbe much more than patient
Define Bactericidal (C)
Kills and/or lyses bacterial cell
Define Bacteriostatic (S)
Inhibits growth -reversible effect
What are the targets for Antibiotics?
METABOLIC REACTIONS
CELL WALL
CELL MEMBRANE
Why can target sites of the Antibiotics be a problem?
Besides the Cell wall, all of the targets are in the host as well as the microbe
How does Sulphonamides (S) antibiotic effect the cell?
By inhibiting Folate metabolism
How does Fluoroquinolones(C) antibiotic effect the cell?
By inhibiting DNA synthesis causing cell death
How does Rifampicin (C) antibiotic effect the cell?
By inhibiting RNA synthesis (transcription), causing cell death
How do Tetracyclines(S) and Chloramphenicol (S) antibiotic effect the cell?
By inhibiting Protein synthesis (translation)
In the cell wall what are the two processes that Antibiotics target and what Antibiotics target these?
Synthesis
•Cycloserines(S)
Stability / integrity
•ß-lactams (C)
•Vancomycin(C)
In the Cell Membrane, what are the two processes that Antibiotics target and what Antibiotics target these?
Stability / integrity
•Polymyxins(C)
•Polyenes(C)
What is the difference between Folate metabolism in bacteria and in Mammalian cells?
Bacteria synthesise folic acid whereas humans obtain folic acid from diet
How does Sulphonamides affect Folate Metabolism?
It inhibits the enzyme which activates the process between Para-Aminobenzoic acid and Dihydrofolic acid, preventing the conversion
How does Trimethoprim affect Folate Metabolism?
It inhibits the enzyme which activates the process between Dihydrofolic acid and Trimethoprim, preventing the conversion
How is Bacterial DNA coiled?
Activating gyrase
Define Anti-gyrase
The process in which super-coiling in bacterial DNA is prevented
What does Rifampicin do in the bacterial cell?
Prevents production of mRNAInhibits transcription
How does Tetracycline Inhibit protein synthesis (translation)?
By acting on the 30s ribosome unit
How does Chloramphenicol Inhibit protein synthesis (translation)?
By acting on 50s ribosome unit
Define ß-LACTAMS
This is a group of Antibiotics which within their chemical structures contain a ß-Lactam ring.
Includes Penicillins and cephalosporins
What does B-Lactams do?
Inhibit final stage of peptidoglycan assembly (cross-linking)
Bind irreversibly to transpeptidase
Induce autolytic enzymes
In B-Lactams what does the R group do?
Gives properties such as acid resistance, membrane transport or resistance to ß-lactamase
What is the Role of Vancomycin?
Binds to D-Ala-D-Ala on peptidoglycan side chain
Block transpeptidation
What is the role of Polymyxin
Disrupts bacterial cell membranes
Why are Antifungal drugs hard to produce?
Fungi are eukaryotes with similar structure function to humans & animals.
Harder to find unique targets
Difficult to treat
Why are Anti viral drugs hard to produce?
- Viruses use the host cells own metabolic processes to replicate
- Even harder to treat as the target is the host.
What is the problem with Nucleoside analogues and give examples
Toxic to host too
Ganciclovir
Zidovudine(AZT)
What is the two different Antibiotic resistance?
Natural/Innate Resistance and Acquired Resistance
Define Natural/Innate Resistance
Variations in the structure of cell envelope/cell wall
Altered binding sites/enzymatic inactivation
Efflux mechanism
Define Acquired Resistance
Mutation
Adaptation
Gene Transfer (plasmids, transposons)
Where the Genes that are responsible for Antibiotic Resistance located?
Chromosome or on plasmid
Define Exclusion
Envelope impervious to antibiotic
Gram-negative bacterial Outer Membrane
Define Excretion
Tetracycline efflux pump, removal of Tetracycline
Define Alter targets
Structure of ribosome (methylation of ribosomal RNA), polymerases and gyrases
Modify metabolic pathway -sulphonamides
Define Destroy antibiotic
B-lactamases open B-lactam ring
Define Modify antibiotic
–Phosphorylation -Streptomycin
–Acetylation –Chloramphenicol
What are the causes of Antibiotic Resistance?
- Over-prescribing
- Non-compliance
- Indiscriminate use of antibiotics e.g supplement feeds in agriculture
What ways can we overcome Antibiotic resistance?
- Identification of the pathogen
- Selection of the antimicrobial agent appropriate for the pathogen
- Is the organism resistant to the prescribed antibiotic
- Drug combinations (penicillin + clavulanic acid)