Antibiotic resistance

Question 1

What does antibiotic resistance increase?

Answer 1

• Increases mortality

- Increases the costs of health care

Question 2

What is enterococci and where does it live?

Answer 2

• Gram-positive bacteria which live in the gut

Question 3

What antibiotic does enterococci have natural resistance to?

Answer 3

• Naturally vancomycin resistance

Question 4

What is acinetobacter and where does it live?

Answer 4

• Gram-negative bacteria which live in gut

Question 5

Where is acinetobacter found at the site of?

Answer 5

• Found at the site of wound infections

Question 6

What is MRSA and where does it live and where is it found?

Answer 6

• Gram-positive bacteria which live in the gut and found in wounds

Question 7

What is the mechanism of antibiotic resistance(Beta lactamase enzyme)?

Answer 7

1. Drug activation
   a. Bacteria have acquired this enzyme which destroys the structure of beta-lactam antibiotics causing it to be inactive
   b. Can no longer use the antibiotics against certain bacteria unless we develop an antibiotic against beta-lactamase enzyme
   c. However, that could potentially just lead to the bacteria acquiring another enzyme which will break down the antibiotics that have been developed
   d. These new enzymes are known as Extended Spectrum Beta-Lactamases = digest and inactivate almost every beta-lactam antibiotic
2. New/mutated target
   a. Mutation in enzyme means drug can no longer bind to the enzyme
   b. The mutated target is RNA polymerase and its mutation results in resistance
3. Intrinsic permeability
4. Overproduction of target
5. Efflux pump
6. Metabolic by pass

Question 8

What are the 4 paths to resistance?

Answer 8

1. Directed at antibiotic itself
2. New/altered drug
3. Altered transport
4. Metabolic bypass

Question 9

How is resistance directed at antibiotic itself?

Answer 9

○ Either by modifying or degrading the drug

Question 10

How is resistance in new/altered drugs?

Answer 10

○ Antibiotic can no longer bind

Question 11

How is resistance developed due to altered transport?

Answer 11

○ Acquisitions of porins/efflux pumps
○ Mutations in porins/efflux pumps
○ Upregulation of efflux pumps which actively pumps drug out faster

Question 12

How is resistance developed due to metabolic bypass?

Answer 12

Bacteria have acquired genes that allow a completely new metabolic pathway which is not inhibited by the drug

Question 13

What are the 3 mechanisms of resistance?

Answer 13

• Natural resistance
• Genetic mechanism(Acquired)
• Non-genetic mechanisms

Question 14

What is prevented of the drug in natural resistance?

Answer 14

• Drug is prevented from reaching target through natural barriers, porins, export pump

Question 15

Comment on gram positive peptidoglycan

Answer 15

• Gram-positive peptidoglycan is highly porous and has no barrier to diffusion

Question 16

What gives gram negative bacteria an advantage to resistance?

Answer 16

• Gram-negative outer membrane acts a barrier which gives an advantage to resistance

Question 17

What is the chromosome mediated genetic mechanism for resistance?

Answer 17

a. Mutation on chromosome
b. Bacteria replicate many times so can generate a large number of spontaneous mutations
c. If mutation is found in target molecule or in the drug uptake system, then it leads to resistance
d. If we continue to take antibiotics then mutants are selected for and become the predominant strain as they’re not killed by the antibiotic

Question 18

What is the plasma mediated genetic mechanism for restistance?

Answer 18

a. Spontaneously random mutant will survive when antibiotic is taken leading to antibiotic resitance
b. Common in gram-negative rods
c. Transferred via conjugation
d. Multidrug resistance

Question 19

What is transformation?

Answer 19

○ Uptake of naked DNA from one bacterium into another

Question 20

What is transduction?

Answer 20

○ Infected by a phage
○ The phage carries a section of DNA from the previous bacterial host which it infected
○ Common mechanism of exchanging genetic information from one bacterium to another

Question 21

What is conjugation?

Answer 21

○ Bacteria cells come together and from pili
§ DNA exchanged through pili
○ Can exchange chromosomal DNA or plasmid DNA

Question 22

What do bacteria with resistance to beta lactams acquire?

Answer 22

Have acquired beta-lactamases with penicillinase which destroys the active part of penicilin

Question 23

What can gram-positive bacteria acquire in the resistance to beta-lactams?

Answer 23

• Gram positive

§ Can acquire alterations of their transpeptidases

Question 24

What can gram negative bacteria acquire in the resistance to beta lactams?

Answer 24

• Gram negative

§ Can acquire alterations of their porins

Question 25

What antibiotic combination has been made to combat resistance to beta-lactams?

Answer 25

An antibiotic combination called Augmentin/Co-amoxiclav has been developed

Question 26

What does the antibiotic combination have a combination of?

Answer 26

A combination of clavulanic acid and amoxicillin

Question 27

What does clavulanic acid inhibit?

Answer 27

Clavulanic acid inhibits beta lactamase enzyme

Question 28

What is amoxicillin ?

Answer 28

§ Amoxicillin is a beta lactam antibiotic

Question 29

What does the antibiotic combination called augmentin /co-amoxiclav bind to?

Answer 29

○ Binds to and inactivates beta lactamases

Question 30

What activity does the antibiotic combination called augmentin/co-amoxiclav have?

Answer 30

Has no anti-bacterial activity of its own and just blocks enzymes so antibiotic can work

Question 31

What does beta lactam pass through in gram negative bacteria?

Answer 31

• Beta-lactam typically passes through the porins in the outer membrane

Question 32

What happens if the porin mutate/new porin type is introduced in gram negative bacteria?

Answer 32

If porin mutate/new porin type is introduced and can no longer pass through the membrane which leads to resistance

Question 33

What could happen to the bacteria which could lead to resistance in gram negative bacteria?

Answer 33

• Bacteria could also mutate/acquire alternative PBP enzyme which leads to resistance

Question 34

What are the mechanisms by which bacteria become more resistant to penicillin?

Answer 34

* Produce penicillinases/beta lactamases that cleave the beta lactam ring * Acquire alternative forms of/or mutations in penicillin binding proteins * Acquire alternative forms of mutations in porins * Acquire alternative forms of mutations in efflux pumps

Question 35

What is the only effective treatment of MRSA?

Answer 35

Only effective treatment of MRSA is Vancomycin

Question 36

What have organisms that have vancomycin resistant acquired?

Answer 36

• Vancomycin resistant organisms have acquired a van operon by transpotition

Question 37

What does the van operon regulate and what does this mean?

Answer 37

• Van operon regulates the biosynthesis of the precursor D-ala-D-lac, instead of D-ala-D-ala which means vancomycin will bind very weakly

Question 38

What are non-genetic mechanisms of resistance?

Answer 38

1. Inaccessibility to drugs | 2. Stationary phase/vegetation and biofilms

Question 39

Why are biofilms of bacteria difficult to treat?

Answer 39

Biofilms of bacteria are very difficult to treat as they form a mucopolysaccharide surface structure which antibiotics can’t get through

Question 40

Antibiotic resistance in neisseria gonorrhoeae

Answer 40

a. Treatment was a single intramuscular injection of penicillin b. Resistance started rising c. New front line drug created called Ciprofloxacin which inhibits DNA gyrase d. Resistance started rising again e. Now use a combined intramuscular injection of ceftriaxone and Azithromycin = starting to see an increase in resistance

Question 41

Antibiotic resistance in carbapenem resistance E.coli

Answer 41

a. Broad spectrum antibiotics of last resort for gram negative bacteria b. New strains destroy antibiotics which lead to resistance c. This is due to it acquiring a new gene