Mechanisms of Antibiotics and Antibiotics Resistance

Question 1

What are the 4 types of resistance?

Answer 1

mutational resistance, natural (intrinsic) resistance, transferable resistance, induced resistance

Question 2

What are the two types of transposable elements and what do they have in common?

Answer 2

The two types of transposable elements are transposons and insertion sequences. They have common inverted short sequences (IR) flanking them, which are essential for inserting on another part of the chromosome

Question 3

How are plasmids different from transposons/insertion sequences?

Answer 3

Plasmids are ds circular DNA that contains 1-2 genes and can self-replicate. Transposons and inserted sequences must exist within a replicon because cannot self-replicate

Question 4

What are integrons?

Answer 4

They are non-mobile DNA elements in bacteria that normally exist within transposons and acquire gene cassettes that contain antibiotic resistance genes. Integons have their own promotor sequences.

Question 5

What do insertion sequences encode?

Answer 5

encode only functions involved in insertion

Question 6

Seven mechanisms of Antibiotic Resistance

Answer 6

1. Enzymatic inactivation
2. Decreased permeability
3. Efflux
4. Alteration of target site
5. Protection of target site
6. Overproduction of target
7. Bypass of inhibited process

Question 7

Which beta-lactam antibiotic serves as a back-up drug in case bacteria are resistant to the others and will be extremely problematic if there’s resistance to it?

Answer 7

Carbapenems: most powerful b-lactam antibiotic

Question 8

What enzymes do b-lactam antibiotics inhibit?

Answer 8

transpeptidase, carboxypeptidase, and endopeptidase

Question 9

What have bacteria acquired to resist b-lactam antibiotics?

Answer 9

They can secrete an enzyme called b-lactamase that will require a serine or zinc at active site to hydrolyze the b-lactam ring.

Question 10

What are the 5 types of b-lactamases?

Answer 10

1. narrow spectrum b-lactamases
2. Extended spectrum b-lactamases (ESBL) against 3rd generation cephalosporin
3. amp C production (some enteric bacteria encode this in their chromosome -natural resistance;ampC is inducible)
4. carbapenemase production (scary b/c carbapenem is our backup beta-lactam abx)
5. major outer membrane protein modification

Question 11

If patient has bacteria with extended spectrum b-lactamases will also put in isolation like someone with MRSA, why?

Answer 11

b/c you don’t want these resistance to spread.

Question 12

Patients with ESBLs (extended spectrum b-lactamases) are treated with

Answer 12

Carbapenems

Question 13

How does MRSA occur? Which gene expression plays a role?

Answer 13

by altering target sites via making modified transpeptidase (a way gram + bacteria can evade b-lactam antibiotics in addition to making b-lactamase). Expression of mecA gene plays a role in MRSA.

Question 14

What is the mechanism of action of beta-lactam antibiotics?

Answer 14

They mimic the D-ala-D-ala residues causing penicillin binding proteins (transpeptidases) to bind to antibiotics as opposed to crosslinking and building the bacterial cell wall.

Question 15

What are the 4 main classes of beta-lactam abx?

Answer 15

1. penicillins
2. cephalosporin
3. monobactams
4. carbapenem

Question 16

List the 6 antibiotics that inhibit protein synthesis and state whether they are bacteriocidal or bacteriostatic

Answer 16

1. tetracycline -bacteriostatic
2. aminoglycoside -bacteriocidal
3. macrolid -bacteriostatic
4. chloramphenicol -bacteriostatic
5. clindamycin -bacteriostatic
6. linezolid -bacteriostatic

Question 17

What’s the main reason that an antibiotic may at some times be bacteriostatic and at other times be bacteriocidal

Answer 17

It depends on the dosage of the abx in comparison to the minimum inhibitory concentration.

Question 18

ESBL (extended spectrum beta lactamases) and KPC (klebsiella pneumonia carbenpenmases) -compare and contrast their spectrum of activity and most common organisms

Answer 18

-Spectrum of activity
ESBL -affect most b-lactam abx except carbapenem
KPC -affect even carbapenem (largest abx resistance spectrum)
-Most common organisms
ESBL -e. coli, proteus, klebsiella
KPC -klebsiella and many gram negative species

Question 19

What is the mechanism of resistance responsible for VRE?

Answer 19

altering cell wall precursor target site; normally, vancomycin works by binding to D-ala-D-ala, but bacteria can change this sequence, preventing binding of vancomycin