Lecture 21 - antibiotics Flashcards
what bacteria caused black death
yersinia pestis
a gram -ve bacterium
what does magic bullet refer to
idea by Paul Ehrlich
- wanted a drug that killed targeted pathogen and leave host unharmed
what was the first drug developed by Ehrlich
salvarsan
which cured syphilllis
what was first commercially available antibiotic
prontosil
what are the 4 targets iof antibiotics
- cell wall synthesis inhibitors
- protein synthesis inhibtors
- nucleic acid synthesis inhibitors
- folic acid biosynthesis
why must duration of therapy be sufficient in bacteriostatic antibiotic
needs time to allow immune defences to eradicate bacteria
whats the name of inhibitors of cell wall synthesis
b-lactam antibiotics
becuase they have a b lactam ring
and they inhibit pepgly synthesis
3 examples of b-lactam antibiotics
- benzyl penicillin
- cephalosporin
- carbapenem
who discovered penicillin
Fleming
how did the first penicillin (penicillin G) have to be administered
injection
cuz destroyed by gastric pH
how does penicillin act
acts as competitive inhibitor of penicillin binding protein (e.g. carboxypeptidase) instead of D-ala - D-ala
so pepgly cant be made
- then pepgly precursors build up and trigger hydrolases to lyse the cell
how was penicillin modified to allow it to affect gram -ve bact
modified to make it less hydrophobic
e.g. amoxycillin
penicillin resistance
b-lactamases
hydrolyse the b-lactam ring so they are inactive
2 ways to counteract penicillin resistance
- combine w/ clavulanic acid (a b-lactamase inhibitor)
- synthesis b-lactamase resistant penicillins e.g. methicillin
mechanism of carbapenem antibiotics
acylate penicillin binding proteins
so inactivating them
(used to treat b-lactamase producing bacteria; so those resistant to penicillin)
how can carbapenem antibiotics target gram-ve ones as well
can enter them via porins
how do carbapenem have to be administererd
intravenously
2 ways carbapenem resistance arose
1) 3 new enzymes that hydrolyse the b-lactam ring
2) reduce influx or increase efflux of the drug
how is MRSA resistant to methicillin
has mecA gene
encodes penicillin binding protein 2A
this has low affinity for B-lactam antibiotics
so they have no effect
what is the one antibiotic that can go against MRSA
vancomycin
vancomyocin mechnism
bind D-ala-d-ala
preventing transpeptidases catalysing the peptide bond
vancomycin resistance how
D-ala exchanged for L-serine or D-lactate
what are aminoglycosides
inhibit protein synthesis by binding to 30s ribosomal subunit
bacteriascidal
how do aminoglycosides cause cell lysis
creates fissures in outer cell memb
- leakage of intracellular contents
- more antibiotic uptake
what are aminoglycosides examples
all the mycins
what type of bact is aminoglycosides effective on
aerobic bacteria
what are side effects of aminoglycosides
kidner and inner ear toxicity
what are tetracyclins
inhibitors of protei synthesis
by binding to 30s subunit
bacteriostatic
what type of cell do tetracyclins penetrate
macrophages
what are macrolides
inhibitors of protein synthesis
bind to 50s subunit
and ONLY for gram +ve cuz gram - easily resistant
how do macrolides work
prevent tRNAs from binding
so polypetide chian cant be made
example of inhibitors of nucleic acid synthesis
fluoroquinolones (e.g. ciprfloxcin)
how do fluoroquinolones work
bind to DNA gyrase
DNA cant unwind properly
inhibit DNA replication
a downside of fluoroquinolones
they affect all bacteria in body
including gut microbiota
what type of grug are sulphonamides and trimethoprim
antimetabolites
how do sulphonamides act
comp inhib of dihydropeterate
so folate synthesis cant occur
3 new antibiotic discovered
- teixobactin - inhibit cell wall biosynth by binding to precursors
- malacidin
- retinoids
