Antibiotic Resistance Flashcards
Describe how antibiotics can be inhibited by drug inactivation or altered targets by bacteria, giving examples
Drug Inactivation: acquired β-lactamase destroys the β-lactam ring in penicillins and cephalosporins
Altered/New Target: acquired mecA gene by MRSA codes for penicillin binding protein 2a. PBP2a target site doesn’t bind methicillin or other β-lactam antibiotics, so isn’t inhibited
Other: ribosomes, porins, DNA gyrase (R+ to quinolones), RNA polymerase (R+ to rifampicin), Mcr1 and colistin can all be altered!
How can altered transport and mass target production inhibit antibiotics?
Efflux Pumps: remove antibiotics quickly. Pumps can either be acquired, or can acquire mutations that allow them to work faster
Antibiotics that competitively inhibit a target can be overcome by mass production of the target-> not enough drug to inhibit the target.
What is metabolic bypass? Use this to explain vancomycin resistance
Metabolic by-pass: bacteria by-pass the part that the antibiotic inhibits
e.g. Vancomycin binding to the terminal D-ala, D-ala unit inhibits peptidoglycan synthesis.
Bacteria can develop a metabolic by-pass by replacing the last D-ala residue w D-lac (lactate) = vancomycin cannot recognise and bind = R+ vancomycin
Give the genetic mechanisms of antibiotic resistance
Chromosome-mediated = spontaneous mutations which become prevalent through selection
Plasmid-mediated = gene exchange between bacteria. Common in gram neg bacteria via conjugation
Material can transfer genetic material by…
Transformation – acquisition of DNA
Transduction – A bacteriophage (viral particle) will infect a bacteria and transfer DNA from its previous host to the new host
Conjugation – sex pilous on 1 bacteria forms a cytoplasmic bridge w another. 1 strand of plasmid DNA transfers between them. Each bacterium replicates the strand to make a complete plasmid.
Describe the resistance to beta-lactam antibiotics with gram-positive and gram-negative bacteria.
What is Co-amoxiclav?
Co-amoxiclav/Augmentin= amoxicillin (a β-lactam antibiotic) and Clavulanic acid (has β-lactam structure but has no antibiotic properties)
Clavulanic acid inactivates b-lactamases – this protects amoxicillin from beta-lactamase-> amox still works
Give the Mechanisms by which bacteria become resistant to penicillin
What are the non-genetic mechanisms of antibiotic resistance?
Inaccessibility to drugs, e.g. abscess or TB lesion: the vascular blood supply is poor resulting in lack of antibiotic delivery to infection site
Stationary phase bacteria/biofilms: not affected by antibiotics which inhibit cell wall synthesis bc they’re not doing anything
How do we prevent resistance?
