Antibiotics 2 Flashcards
3 modes of AMR (antibiotic resistance)
Intrinsic resistance
Acquired resistance
Tolerance
Intrinsic resistance
Bacteria you’re looking at can’t be killed by that drug
e. g. bacteria lack target structure or possess an impermeable cell envelope
- Gram-negatives are intrinsically resistant against many penicillins
Acquired resistance
Renders a formally sensitive bacterium resistant
e.g. through spontaneous mutation
OR by picking up resistance determinants
(horizontal gene transfer)
Tolerance
Cells are temporarily in a physiological state that renders them ‘resistant’
- endospores, dormant cells or cells in biofilms
= not normally susceptible to antibiotics
4 main mechanisms of acquired AMR
Change the target
- Spontaneous mutations (e.g. in enzymes)
- Acquisition of alternative genes or pathways
Degrade the AB
-Via hydrolytic enzymes
Modify the AB
- Modifying enzymes
(e. g. acetyltransferases)
Export the AB
- Via active transporters
Changing the target
- 3 ways
Spontaneous point mutations
Acquisition of an alternative gene
Acquisition of an alternative biosynthetic pathway
Changing the target
- spontaneous point mutation
> example of AB and how they work
Quinolones e.g. Ciprofloxacin
Bind to GyrA subunit of DNA gyrase near where it would normally bind to DNA
-> inhibits DNA gyrase
Changing the target
- spontaneous point mutation
> resistance against Quinolones
Point mutation in QRDR region abolishes quinolone binding
-> gyrase is still active but now resistant
QRDR
Quinolone resistance determinant region
DNA gyrase
- how does it work?
2 subunits - GyrA and GyrB
slot into each other
-> slot around DNA
-> controls supercoiling
Point mutations
- transferal
Mutations now on chromosome
-> passed onto daughter cells
NOT normally transmitted horizontally between bacteria
Changing the target
- acquisition of an alternative gene
> example of an AB and how they work
Penicillin
Bind and irreversibly block transpeptidases (PBPs = penicillin binding proteins
- )
Changing the target
- acquisition of an alternative gene
> some forms of PBPs
Lower substrate affinity
-> less likely to bind penicillin and become inactivated
= resistance
Acquisition of an alternative gene
- MRSA
> what does it stand for?
> resistance
Methicillin Resistant Staphylococcus aureus
Possesses mecA gene
- encodes low-affinity PBP
= PBP2a
mecA is part of mobile genetic element - SCCmec
- can become v large + carry multiple resistance genes against different classes of AB
Acquisition of an alternative gene
- MRSA
> spread of mecA
As part of SCCmec
- > can be readily passed between different staphylococci
- > spread of resistance
Changing the target
- acquisition of an alternative biosynthetic pathway
> example of an AB and how it works
Vancomycin
Bonds to the terminal D-Ala-D-Ala of peptidoglycan precursors
-> inhibits transpeptidation
Acquisition of an alternative biosynthetic pathway
- Vancomycin resistance
Synthesis of alternative peptidoglycan precursors
- alternative ending to D-Ala-D-Ala
e.g. D-Ala-D-Lactate
Can’t be bound by vancomycin