Antibiotics 1 Flashcards
Cell Wall Synthesis Inhibitors I and II
What is the function of a bacterial cell wall?
Protects bacterial cells from the external environment.
Provides shape and rigidity to the cell.
What is the difference between gram-negative and gram-positive bacteria?
Different components.
Gram-negative: Thin cell wall found between inner and outer membrane.
Gram-positive: Thicker cell wall found on the outside of the cell membrane.
What is Peptidoglycan?
it is a polymer of peptide-linked chains of amino sugars.
a major component of most cell walls
Describe the structure of peptidoglycan.
The molecule consists of parallel polymers of disaccharides called glycan crosslinked with peptide chains of 4 amino acids
Long chains of peptidoglycan consist of repeating units of disaccharide made up of N-acetylglucosamine and N-Acetylmuramic acid.
n-acetylmuramic acid has a string of four amino acids which form cross-linking bridges with each other to create the rigidity and strength of the cell wall
The strength of bonds formed can vary between different bacteria
Describe the first phase of bacterial cell wall synthesis.
Begins inside the cell in cytoplasm with small peptidoglycan precursor molecules. Amino acids sequentially bind to N-acetyl muramic acid, usually finished with the addition of 2 alanine molecules attaching to form alanine terminus to form N acetylmuramyl (UDP) and N-glucosamine in the cytoplasm.
Describe the second phase of bacterial cell wall synthesis.
Precursor lipid intermediates synthesised. Lipid 1 complex forms when UDP molecule moves towards cytoplasmic membrane then binds to the membrane acceptor molecule (bactoprenol) via binding of one phosphate from the UDP and release of the UMP molecule.
N-acetylglucosamine transferred onto lipid complex releasing an intact UDP to form the lipid 2 complex.
What does the lipophilic bactoprenol molecule do next?
Aows transport of lipid 2 complex through the cytoplasmic membrane and extends the situated sites for incorporation, extending into the growing peptidoglycan wall.
Describe the final stage of bacterial cell wall synthesis.
Takes place on the outer side of cytoplasmic membrane involvng polymerisation of the newly sythesised dissacharide peptide unit.
This is incorporated into the growing cell wall via trans glycolstlation and transpeptidation reactions.
These reactions are cataysed by the penicilin binding poretins formt eh glycosidic and peptide bonds on the peptidoglycan cell wall.
What is the role of the transglucosylase enzyme in the 3rd phase of bacterial wall synthesis?
Binds together the N acetyl glucosamine of the incoming peptidoglycan precursor molecule and the end of the n-acetylmuramic acid of the growing peptidoglycan chain.
How does the cell wall become strong?
Cross-links formed between the peptides in the peptide chains by this enzyme.
Binds between the lysine of one chain and the penultimate alaine of a second chain causing the terminal alanine to be cleaved - a strong flexible mesh of peptidoglycan formed.
This is the basis of the gram-positive cell wall.
Describe the fate of bactoprenol after the 3rd phase of bacterial cell wall synthesis.
Recycled via loss of additional phosphate that was gained when N-acetylmuramic acid pentpeptide and is relocated inside the cytoplasmic membrane.
This makes it ready to transport further precursor molecules over the membrane.
Describe the purpose of antibiotics.
Inhibit bacterial cell wall synthesis causing bacterial growth inhibition and cell death.
Give some examples of B-lactam antibiotics
penicillin, cephalosporins and carbapenems
Describe the structure of B-lactam antibiotics
All have B lactam ring
Different penicillin made via modification of its sidechain
Complex cephalosporins have two modifiable side chains
Carbapenems have three modifiable side-chains
How was penicillin first produced?
By Mould Penicillium notum - name later changed to peicillium chrysogensum.
How was penicillin developed?
Penicillin found to produce 4 different types of penicillin - Pen G (in greatest quantity), K, F, and X
Penicillin preparations were isolated- found that some penicillin preparations were less effective at clearing some infections due to different strains, growth conditions and methods of purification caused by different types of penicillin present in different ratios.
Why was penicillin G more produced? What is the relevance of penicilin G?
Penicillin G is more active against Treponema pallidum (causative agent of syphilis, thus more effective to treat it)
Prompted synthesis of individual pure penicillin preparations to known F,G,F,K types for efficacy testing
Why were/are side chains of penicillins modified? What properties does this give modified penicillins?
Modifications to sidechains of each type gave different properties e.g different levels of hydrophobicity
and
Differing effectiveness against specific bacteria and relative toxicity to the host
List 4 limitations of penicillins.
Narrow spectrum of activity.
Hypersensitivity/allergy to penicillin- penicillin allergies are the most common cause of drug allergic reactions.
Sensitivity to gastric acid.
Kidneys rapidly remove it from mammalian systems.
How does a narrow spectrum of activity affect penicillin efficacy?
natural penicillin’s only had activity against a narrow range of organisms – ineffective against some of the most frequent causes of modern-day infection
What does an allergic reaction to penicillin look like?
rashes, swollen faces, can be as serious as anaphylactic shock.
side effects of penicillin can be mistaken for an allergic reaction.
How is penicillin’s sensitivity to gastric acid solved?
Addition of protective coatings to the drug that shields it from stomach acid and will dissolve in the intestinal tract where the drug can become active
Modification of penicillin e.g Penicillin G modified to penicillin V making it more stable in acidic conditions – made if less active against infections.
How is the issue of rapid penicillin removal from mammalian systems solved?
Larger doses are given to patients to raise penicillin levels within the body due to its low toxicity
Co-administer a second drug (e.g probenecid) - found to increase serum level of antibiotics by reducing excretion due to competition for active sites of excretion.
these methods can increase the time that antibiotics are maintained in the blood stream for 1-24 hours
