JAL L3 Mechanisms of resistance Flashcards
Organisms of particular concern: (5)
E. faecium S. aureus K. pneumoniae P. aeruginosa Enterobacter
2 e.g. of multidrug resistant micro-organisms?
E.coli
M. tuberulosis
Genetic mutations mostly confer low/high level resistance?
low (some produce resistance to 1 antibiotic)
new genetic material is usually acquired how?
on plasmids through conjugation.
How does conjugation occur?
Mobile plasmid cell produces pilus (pokey stick thing) that connects to another cell, pulls them together and plasmid transfers.
Three main mechanisms of resistance?
Inactivate drug
Alter drug target site
Alter drug transport
resistance to β-Lactam occurs mainly through….
β-Lactamases
(may be chromosomal or plasmid-mediated)
(some have limited spectrum e.g. just penicillins, others wider)
β-Lactamases are more of a problem in gram positive or negative?
negative (β-Lactamases in the periplasmic space). Gram positive requires a higher density of cells to work.
e.g. of β-Lactamase inhibitors?
Clavulanic acid (co-amoxiclav). Prolongs the life of the betalactam drug. Also: tazobactam & sulbactam
MRSA is resistant because….
altered penicillin binding proteins.
β-Lactams can also have resistance through altered uptake, how?
reduced no or size of porins,
reduces permeability and prevents uptake.
How does resistance to vancomycin occur?
Altered target site - change in terminal amino acid from
D-Ala-D-Ala to D-Ala-D-lactate
> unstable complex, 4, instead of 5 H bonds.
Sulphonamide resistance occurs from…
plasmid encoded enzyme target (dihydropteroate synthetase) has reduced affinity for the drug.
Trimethoprim resistance occurs from…
chromosomal expression of enzyme with reduced affinity for the drug (dihydrofolate reductase).
Resistance to aminoglycosides occurs from 3 enzymes inactivating drug by doing what…..
Acetylases (adding acetyl to NH2)
Adenylylases (adding AMP to OH)
Phosphorylases (adding phosphate to OH)
