lecture 5 - antibiotic control of bacterial infections Flashcards
Why do antibiotics have a differential toxicity for bacterial cells vs human/eukaryotic cells?
The bacterial cells have targets not present in eukaryotic cells OR target is sufficiently different in eukaryotic cells
What are the 3 categories of antibiotic, based on cellular target?
Cell wall synthesis, nucleic acid synthesis, protein synthesis
What is the difference between the gram-positive and gram-negative cell wall?
gram-positive: thick peptidoglycan layer
gram-negative: thin peptidoglycan layer with outer lps membrane
What protein is a target for penicillin binding, and is responsible for peptide side chain cross-linking in the peptidoglycan layer of the bacterial cell wall?
penicillin-binding protein
What are Beta-lactams?
A class of antibiotic that all contain a beta-lactam ring in their chemical structure
What are the 4 classes of Beta-lactam antibiotics?
Penicillin, cephalsporin, carbapenem, monobactam
What chemically differentiates the classes of Beta-lactam antibiotics?
The R side chains of the Beta-lactam rings
What protein is produced by bacteria and makes them resistant to some classes of Beta-lactam antibiotics?
Beta-lactamases - they break down beta-lactams
What class of beta-lactam is most likely to cause an allergic reaction?
Penicillin
What is the function of penicillin-binding protein?
Crosslinking of the peptide side chains of peptidoglycan backbone in the bacterial cell wall
What are the 2 key classes of glycopeptides (antibiotics)?
vancomycin, teicoplanin
What class of bacteria are affected by glycopeptide antibiotics, e.g. vancomycin ?
gram-positive only
Why are glycopeptide antibiotics unable to target gram-negative bacteria?
They are unable to penetrate the gram-negative outer membrane
How do glycopeptides kill bacteria?
They bind to components of the bacterial peptidoglycan layer to inhibit cross linking
How do protein synthesis inhibitor antibiotics work?
By binding to RNA in the ribosome functional sites to prevent bacterial protein synthesis
Why do protein synthesis inhibitors have differential specificity between host cells and bacterial cells?
The prokaryotic and eukaryotic ribosomes are structurally different so the human ribosome is not a target
Which class of antibiotics include antibiotics that target folate synthesis?
Nucleic acid synthesis antibiotics
How do folate synthesis targeting antibiotics work?
They competitively inhibit enzymes in the folate synthesis pathway preventing the production of tetrahydrofolic acid, which is essential for nucleic acid synthesis
How do fluoroquinolone antibiotics work?
They inhibit bacterial type II topoisomerase enzymes which inhibits DNA replication
What is the function of type II topoisomerase enzymes in bacteria?
They introduce negative supercoils that are required for bacterial DNA packaging
How does Rifampicin antibiotic work?
Inhibits RNA synthesis by targeting DNA polymerase
How does the antibiotic metronidazole work?
Makes breaks in bacterial DNA preventing nucleic acid synthesis, but leaves human DNA intact
What are prodrugs?
Drugs that become active once they have entered the body
