Lecture 14: Mechanisms of Resistance to Antibiotics

Question 1

What is intrinsic or natural resistance to antibiotics?

Answer 1

innate ability through inherent structural or functional characteristics

Question 2

Which two bacteria have innate antibiotic resistance?

Answer 2

M. tuberculosis

Pseudomonas aeruginosa

Question 3

What is mutational resistance to antibiotics? How do these mutation arise?

Answer 3

chromosomal muation

• random/spontaneous
• exposure to antibiotic

Question 4

How does acquired antibiotic resistance happen?

Answer 4

horizontal gene transfer - neighboring bacteria swap genetic material

Question 5

Where are many genes for antibiotic resistance located?

Answer 5

Plasmids, transposons, or integrons

Question 6

What are the three methods of horizontal gene transfer?

Answer 6

Transformation
Conjugation
Transduction

Question 7

What are the seven identified mechanisms of antibiotic resistance

Answer 7

enzymatic inactivation
decreased permeability
efflux
alteration of target site
protection of target site
overproduction of target
bypass of inhibited process

Question 8

Beta lactamases (penicillinases) employ which mechanism of antibiotic resistance?

Answer 8

enzyme inactivation - split amide bond of Beta-lactam ring

Question 9

Where are bla (Beta-lactamase genes) encoded?

Answer 9

transferable genes (plasmids, transposons), integrons

Question 10

What are Extrended-Spectrum Beta-lactamases (ESBLs)?

Answer 10

resistance to 3rd gen cephalosporins, but do not affect carbapenems

Question 11

What are common ESBLs?

Answer 11

Kelbsiella, E coli, Proteus, other Enterobacteriaceae

Question 12

Which antibiotic is used to treat ESBLs?

Answer 12

carbapenem

Question 13

What are Amp C beta-lactamases?

Answer 13

chromosomal enzymes for resistance

not susceptible to beta-lactamase inhibitors

Question 14

Where are Amp C beta-lactamases found?

Answer 14

Enterobacteriaceae, Kelbsiella, E coli

Question 15

which category of beta-lactamases offer the largest antibiotic resistance spectrum?

Answer 15

carbapenemases

Question 16

Which four classes of antibiotics are used against a beta-lactamase producing organism?

Answer 16

Penicillinase-Resistant Penicillins
Beta-Lactamase Inhibitors and Inhibitor Combinations
Extended Spectrum Cephalosporins (3rd and 4th gen)
Carbapenems

Question 17

How does decreased permeability of bacterial membranes work as a mechanism of antibiotic resistance?

Answer 17

alter porins so antibiotics aren’t compatible

larger, more negative, more hydrophobic antibiotic molecules are less likely to get through

Question 18

How does antibiotic efflux work as a mechanism of antibiotic resistance?

Answer 18

moved out of cell

Question 19

What two common classes of antibiotics are effluxed from bacteria as a mechanism of resistance?

Answer 19

tetracycline

beta-lactams

Question 20

What kinds of target sites do bacteria alter as a mechanism of resistance?

Answer 20

Ribosomal target sites
Cell wall precursor target sites
Target enzymes
Protection of target sites

Question 21

from which class of bacteria did vancomycin-resistant S. aureus acquire the gene complex for altering cell wall precursor target sites?

Answer 21

Enterococci

Question 22

What target sites can bacteria alter to be resistant to beta-lactams?

Answer 22

alter Penicillin Binding Proteins

Question 23

What gene confers MRSA its resistance? what type of resistance is this?

Answer 23

mecA gene - on a cassette

alteration of target enzymes

Question 24

Give an example of how altered metabolic pathway mechanism of resistance works

Answer 24

Enterococci needed folic acid
Antibiotics were made to inhibit folic acid (ex. sulfa drugs)
Enterococci became folate auxotrophs - no longer required folic acid, resistant to effects of antibiotic