Resit- Antibiotic Resistance
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Differential toxicity
Based on the concept that the drug is more toxic to the infecting organism than to the host
Antibiotics
Substance produced by a microorganisms that in small amounts inhibits the growth of or kill bacteria
When was penicillin discovered in
1928
What makes an ideal antibiotic
Appropriate spectrum of activity for clinical setting Have no toxicity yo the host -be well tolerated Doesn’t induce hypersensitivities Rapid and extensive tissue distribution Relatively long half life=less frequent doses,better outcomes Low propensity for development of resistance =4reduced likelihood that bacteria or other microbes will evolve or adapt to become resistant to a particular drug or treatment over time Free of intersections either other drugs Relatively inexpensive Convenient inexpensive
Narrow spectrum of activity
Drug is effective against a limited number of species
B-roads spectrum of activity
Drug is effective against a wide variety of species
Mimiumum inhibitory concentration
Minimum concentration of antibiotic required to inhibit the growth of test organism
Minimum bactericides concentratin
Minimum concentration of antibiotic required to kill the test organism
Bacteriostatic
Inhibits growth
Bactericidal
Kills bacteria
Prophylaxis
Antimicirobial agents are administered to prevent infection
Treatment
Anti microbial agents are administered to cure existing or suspected infection
Antibacterial target sides(eg antibiotics)
Inhibition of cell wall synthesis eg pencilling Inhibition of nuclei acid synthesis Disruption of cell membrane function Inhibition of protein synthesis Action as anti metabolites
Bacterial cell wall
Contains Peptidoglycan(network of sugar polymers cross linked by polypeptides. Made of 2 monosaccharides NAG and NAM which are related to glucose)
Role of bacterial cell wall
Maintains cell shape Protects cell Prevents cell from bursting in hypotonic environment
How does penicillin work
Penicillin has a b lactam ring that resembles the structure of the dipeptide Penicillin binding protein mistakenly binds to penicillin instead of the actual substrate Penicillin convalently binds to the active site of PBP This inactivates the transpeptidase enzyme and as a result the real d-ala d-ala dipetide cant be processed so peptide bond isn’t formed and no cross linking occurs The cel wall weakness ,bacterium bursts and it dies
What colour does gram positive bacteria stain
Purple as the thick peptidoglycan traps crystal violet which makes the red safranin dye
What colour does gram negative bacteria stain
Red as due to the small peptidoglycan layer crystal violet is Easily rinsed away
2 classes that both affect the inhibition of cell wall synthesis
1) b lactams such as penicillin or cephamycins 2)glycopetides such as vancomycin
How do antibiotics in the class glycopeptides such as vancomycin work
-glycopeptides bind to teh d-ala d-ala terminal. Of the peptide chains in the peptidoglycan precursors of bacterial cell walls -the binding blocks the access to pencillin binding protein -pencilin binding protein can’t cleave the terminal. D-ala or form the peptide cross links between peptidoglycan strands -this prvenmgts cross linking of the bacterial cell wall causing the bacteria to not be able withstand osmotic pressure and burst
Role of the cell membrane
Selective permeability Large molecules such as proteins can’t pass however smaller molecules such as water or gasses can
Role of outer membrane
Selective barred Contains proteins for transport Lipopolysaccahrdie for bacterial defence Allows selective uptake and efflux
Mechanism of actions of antibiotics that work by disturbing cell membrane
They carry a positive charge and because of that they are attracted to the negative charge of the lipopolysaccharide(LPS) The antibiotic binds to LPS ans inserts itself into the bacterial membrane. It displaces divakent cations like mg2+ ca2+ that stabilise the membrane This disrupts the phospholipid bilayer and may form pores or channels in the membrane This results in leakage of cellular contents and eventually results in lysis
Role of nucleoid
Dna replication,transcription