Mechanisms of Antimicrobial Resistance Flashcards
Describe the difference between intrinsic and acquired antibiotic resistance and list ways a bacterium may acquire antibiotic resistance.
Intrinsic- Properties of bacteria don’t allow for antibiotic targeting.
Ex Gram - organisms and Vancomycin. Vanc cant penetrate Gram - outer membrane.
Acquired- Genetic mutation or acquiring new genes.
Ex: plasmid, transposon, or bacteriophages.
Which bacteria use porins for resistance? How do porins work?
- Found in the outer membrane of gram-negative bacteria
2. Porins selectively take in nutrients/drugs. Change in number or configuration of porins can effect drug activity.
Which bacteria use efflux pumps for resistance? How do they work?
- Both gram-positive and gram-negative organisms.
2. They pump drug out from cytoplasm.
Which protein cross links peptidoglycans? What motif is cleaved during cross linking?
Penicillin Binding Proteins (PBPs)
D-Ala D-Ala motif is cleaved.
How do β - lactam antibiotics work?
β-lactam antibiotics act by irreversibly inhibiting PBPs thereby inhibiting peptide cross-linking and peptidoglycan synthesis.
How do bacteria become resistant to β - lactams?
- Break down the drug via B lactamase
2. Modify PBP to have lower binding affinity for b-lactam.
In which bacteria are β-lactamases found?
BOTH gram-positive and gram-negative organisms.
In general, the BROAD spectrum β-lactamases are found in gram-negative bacteria.
Which bacteria are Narrow spectrum β-lactamases? Which antibotics are they resistant to?
- Staphylococci
* 2. E. Coli/ H. Influenza
* 3. Klebsiella pneumonia
* newer resistance- prompted 2nd and 3rd gen celphalosporin devel.
Resistant to penicillin and ampicillin
What is a difference between Narrow spectrum β-lactamases and ESBLs?
ESBL= Extended spectrum
ESBLs can attack cephalosporins
Where is the ampC gene found in ampC-encoded β-lactamases?
AmpC found in the CHROMOSOME of certain Gram (-) rods: Enterobacter, Pseudomonas, and a few others.
Why is ampC special?
Encodes for cephalosporinase. Can hydrolize penicillin and cephalosporins.
Also, it can be induced or constitutively expressed.
How is ampC expression determined?
Basically ampC isn’t expressed all the time, but if it develops a mutation, it can be expressed all the time and be permanently resistant to a ton of antibiotics.
What drug is used to treat a bug (most commonly Enterobacter strains) with constitutive expression of ampC?
Carbapenems
What is KBC and what does it do?
Klebsiella pneumoniae carbapenemase:
Hydrolyzes ALL B-lactams and Carbapenems.
Found in PLASMIDS
What are the 2 mechanisms for developing Altered penicillin-binding proteins (PBPs)?
- acquiring mecA gene (in staphy bacteria)–> alters binding affinity (when present in staph–>MRSA)
- Mosaic PBPs (strep and gono)- DNA transformation alters protein structure
Which type of altered PBP resistance is generally a slow process?
Mosaic PBPs
How does Vancomycin work?
It binds to the D-Ala motif and prevents cleaving and thus, cell wall synthesis.
How do bacteria become resistant to Vancomycin?
- Modifying the target in Enterococcus (VRE). Changes the D-Ala Motif to D-ala D lac
- Preventing drug-target interaction by binding free Vanc (Staph A.)
How do bacteria become resistant to macrolides?
- Di-methylating target ribosome (erm)
2. Efflux pumps
How do bacteria become resistant to Flouroquinolones?
Modifying target via point mutations in gyrase/topo
What is erm resistance?
Erm gene encodes demethylase which confers resistance to CLINDAMYCIN and MACROLIDES.
Why is the D-test used?
To test resistance to macrolide and sensitivity to clindamycin. Also can tell if it is via efflux pump or constitutive erm expression.
How can you tell if resistance is via efflux pump or constitutive erm expressed (in d-test)?
If bacteria has inducible erm system, then the zone of clearing around clindamycin disk (on agar plate) is blunted and appears like a D instead of a circle.
Efflux= Regular resistance pattern (circle around antibiotic)
*Remember this plate from lab?
