Mechanisms of Resistance to Antibiotics

Question 1

Types of bacterial resistance

Answer 1

1. Intrinsic/Natural - inherent in the structure
2. Mutational - spontaneous or due to insufficient antibiotic exposure.
3. Acquired -genetic gene transfer. through transposons, transduction, plasmids, integrons

Question 2

transformation, transduction, conjugation

Answer 2

transformation - uptake of naked DNA
transduction - transfer DNA by bacteriophage
conjugation - transfer plasmids via sex pili; most common

Question 3

insertion sequences and transposons

Answer 3

insertion sequences - jump around on particular chromosome or plasmid. have promoters; put gene you want expressed next to it
transposons - jumping genes
integrons - capture genes for resistance
*all often have resistance genes

Question 4

mechanisms by which bacteria resist antibiotics

Answer 4

1. Enzymatic activation
2. decrease permeability
3. efflux
4. alter target site
5. protect target site
6. overproduce target
7. bypass inhibited process

Question 5

classifications of B lactamases

Answer 5

B lactamases inactivate B lactam antibiotics by splitting amide bond on ring

• 4 classes A, B, C, D based on AA structure
• also classified based on activity:
  1. ESBL
  2. AmpC B lactamases
  3. Carbapenemas
  4. Narrow spectrum B lactamases

Question 6

ESBL

Answer 6

• resist 3rd generation Cephalosporins and monobactams
• in Klebsiella, E coli, Proteus
• Carbapenems and cephamycins can be used against them

Question 7

Amp C B-lactamases

Answer 7

• resist penicillin, narrow spectrum cephalosporins, oxymino B lactams and cephamycins
• in Enterobacteriacae (other than Klebsiella and E coli)
• Amp C enzymes are hard wired into chromosomal genes

Question 8

Carbepenemas

Answer 8

• largest resistance spectrum
• hydrolyze carbapenems, penicillins, cephamycins, oxyminocephalosporins
• in K pneumoniae, CRE

Question 9

narrow spectrum B lactamases

Answer 9

-resist penicillins and narrow spectrum cephalosporins

Question 10

Penicillin resistant penicillins

Answer 10

• for MRSA and Staphylococcus epidermidis

- structure makes them resistant to penicillinase produced by Staph

Question 11

overcoming B lactamase

Answer 11

1. penicillin resistant penicillins
2. B lactamase inhibitors
3. 3rd and 4th generation cephalosporins
4. Carbapenams

Question 12

B lactamase inhibitors

Answer 12

-irreversibly bind to B lactamase, prevent hydrolysis B lactam in antibiotic and restore antibiotic activity
-not a good antibacterial on its own
ex: augmentin (clavulanic acid + amoxicillin)
also sulbactam and tazobactam

Question 13

MRSA

Answer 13

methicilin resistance

• mec A gene codes PBP2a, protein with low affinity for B lactam antibiotics
• resists all B lactam antibiotics, even those with B lactamase inhibitor

Question 14

VRE

Answer 14

vancomycin resistant enterococci
-vancomycin is a glycopeptide that binds D-ala - Dala on peptidoglycan precursor
-resistant enterococci have altered Dala-Dala so vancomycin cant bind
= an example of altering target site