Flashcards in Control of bacterial infections Deck (14):
principles of controlling bacteria?
1 - reduce exposure - sanitation
2 - reduce susceptibility - vaccination
3 - chemotherapy - antibiotics
first use of antibiotics?
antibiotics that target cell wall? action
beta-lactams eg penicillin and cephalosporins
- bind active site of transpeptidase to irreversibly inhibit peptidoglycan crosslinking causing cell lysis.
- vancomycin blocks access to the transpeptidase
how do antibiotic inhibit translation
1- tetracycline binds 30s and prevents binding of amino acyl tRNA
2 - chloramphenicol binds 50s and inhibits peptidyl transferase activity
3 - aminoglycosides (gentamicin, neomycin) alter conformation of 16s rRNA in 30S subunit to inhibit tRNA selection and peptide elongation
how do antibiotics inhibit folate synthesis
2 enzymes targeted in the pahtway that generates it for purine and hence DNA synthesis.
1 - dihydropteroate synthase - sulfonamide (compete with the pABA substrate)
2 - dihydrofolate reductase - trimethoprim (binds and inhibits it)
how do antibiotics inhibit nucleic acid synthesis?
1 - fluroquinolones (ciprofloxacin) inhibit gyrase and topoisomerase used to control DNA topology during replication and transcription.
2 - rifampicin complexes with DNA dependent RNAP, blocking transcription
a god example of antibiotic resistance?
E coli causing septacaemia and meningitis are becoming increasingly resistant to the fluoroquinolone ciprofloxacin.
mechs via which antibio resistance arises
acquisition via conugation, transduciton or transformation.
selected for by exposure
4 mechs of antibiotic resistance
1 - enzyme mediated inactivation
2 - alteration of target
3 - metabolic by-pass
4 - efflux pumps
how do bacteria inactivate antibiotics
with enzymes. eg chloramphenicol by chloramphenicol acetyltransferase
- beta-lactamases cleave penicillins
how do bacteria alter a target to confer antiobiotic resistance
mutation so that it no longer binds effectively. eg ribosome mutation for streptomycin resistance.
- alternative penicillin binding proteins in peptidoglycan. inc vancomycin resistance in many gram positive.
how do bacteria use metabolic bypass to confer antibiotic resistance
an alternative enzyme for the same pathway to replace that being blocked.
eg plasmid encoded DHFR for folate synthesis that has 1000-fold lower affinity for trimethoprim.
how are drug efflux pumps used
determines multidrug resistance eg in gram -ve pseudomonas and E. coli
- tripartite pumps. drugs bind the inner membrane transporter eg an ATPase or proton antiporter, and are ejected into a unique TolC exit duct which spans the periplasm and outer membrane to eject the drug.