Antibiotic Resistance

Question 1

Differentiate between biological and clinical resistance

Answer 1

Biological resistance:
- refers to changes that result in REDUCED SUSCEPTIBILITY of an organism to a particular antimicrobial agent

Clinical resistance
- the point of biological resistance at which the DRUG (antimicrobial) is NO LONGER EFFECTIVE for clinical use

Question 2

What are shortcomings of detecting Antimicrobial resistance?

Answer 2

Biological resistance is a slow process, it is sometimes undetectable by current lab procedures/technology

Question 3

Define environmentally-mediated resistance. What are some factors?

Answer 3

Resistance that results directly from physical/chemical characteristics of an environment

Factors
- pH
- anaerobic atmosphere
- Cation concentration
- thymidine content

Question 4

What factors DECREASE the activity of the following antibiotics
Erythromycin/ Gentamicin
Tetracyclines
Aminoglycosides

Answer 4

Erythromycin/gentamicin
- low pH

Tetracyclines
- high pH

Aminoglycosides
- low pH
- anaerobic environment
- cation presence

Question 5

What is the MOA that cations decrease activity of aminoglycosides?
What bacteria?

Answer 5

Cations (Mg2+ and Ca2+) and aminoglycosides (AG2+) compete for the NEGATIVELY charged binding sites on the outer membrane surface of PSEUDOMONAS AERUGINOSA

Question 6

Define microorganism-mediated antimicrobial resistance

Answer 6

Resistance that results from genetically encoded traits of microorganism
- can be intrinsic or acquired resistance

Question 7

Define intrinsic resistance. Characteristics?

Answer 7

• resulting from the normal genetic, structure, or physiologic state
• natural
• Predictable
• helps in identifying the microorganism
• Helps in antibiotic selection for the battery for testing against specific organisms

Question 8

Give examples of drugs with intrinsic resistance to aerobic bacteria and gram negative bacteria

Answer 8

Aerobic bacteria
- not able to anaerobically reduce metronidazole

Gram negative bacteria
- vancomycin cannot penetrate this

Question 9

Define acquired resistance. characteristics?

Answer 9

• results from changes in genetics of the microorganism that alter physiology and structure
• unpredictable
• involves genetic change or exchange

Question 10

Define horizontal gene transfer. Give examples & explain them (3)

Answer 10

gene transported between bacteria, using plasmids or transposons

1. Conjugation: direct exchange of DNA (sex, mating)
2. Transduction: bacteriophage (virus that infects bacteria). if the virus is able to infect a bacteria, they are able to transfer genetic material
3. Transformation: acquisition of DNA

Question 11

Give examples of major mechanisms of resistance (4)

Answer 11

1. Decreased intracellular antibiotic uptake
2. Inactivating antibiotics by enzymes
3. Alteration of the antibiotic target site
4. Inc. celluar efflux of antibiotic

Question 12

Explain how resistance to Beta-lactamase work in enzymatic destruction. Give an examples

Answer 12

1. B-lactamases open the antibiotic’s B-lactam ring
2. Its altered structure prevents effective binding to penicillin-binding proteins
   - this is needed for cell wall cynthesis
3. As a result, cell wall synthesis is able to continue

In other words: Enzymatic destruction of antibiotics
- beta-lactam ring in antibiotic inhibits cell wall synthesis in bacteria, resistant bacteria open the ring to continue making its cell wall

Ex. Carbapenemases are active against carbapenem drugs

Question 13

Explain how resistance to Beta-lactamase work in altering the target.

Example of a bacteria that is resistant to methicillin and other B-lactams?

Answer 13

1. Bacteria changes genes that encode for different cell wall synthesizing enzymes (ex. Penicillin-binding proteins PBPs)
2. The new PBPs continue their function even in presence of B-lactam (they don’t care)

Ex.
Staph. Aureus

Question 14

Explain how resistance to Beta-lactamase work in decreased uptake of B-lactams? In what type of bacteria? Example?

Answer 14

1. Changes in the # OR characteristics of the outer membrane porins that B-lactam use to get in
2. Less B-Lactam gets in = bacteria resistance

Ex.
Pseudomonas resistanct to imipenum

Question 15

Explain glycopeptide MOA then MOA of resistance? What bacteria does it mainly involve? What antibiotic is it resistant to?

Answer 15

Mainly involves enterococci with vancomycin

MOA of glycopeptide (found in antibiotic)
1. bind amino acids in the cell wall to prevent the addition of new units to the peptidoglycan

MOA of glycopeptide resistance
1. Produce altered cell wall precursors –> do not bind enough vancomycin
2. Less vancomycin binded = allows peptidoglycan layer synthesis produced (bad)

Question 16

Explain resistance to aminoglycosides by enzymatic modification. What antibiotics ahve aminoglycosides

Answer 16

Aminoglycosides: gentamicin, tobramycin, streptomycin

1. Modifying enzymes alter various sites on antibiotic (aminoglycoside) by:
   - enzymatic phosphorlyation of hydroxyl group OR
   - enzymatic acetylation of amine groups
2. Alterations cause decreased affinity for 30S ribosomal subunit –> allows protein synthesis to continue in bacteria (bad)

Question 17

Explain resistance to aminoglycosides by altered target

Answer 17

mutations in ribosomal binding site = diminishes the ability of aminoglycoside to bind

Question 18

Explain resistance to aminoglycosides by decreased uptake pathways

Answer 18

1. Changes in the # OR characteristics of the outer membrane porins that aminoglycosides use to get in
2. Less aminoglycoside gets in = bacteria resistance

Question 19

How does antibiotic resistance spread? **read infographic (2)

Answer 19

• Intrinsic development: animals and humans get antibiotic –> develop resistance in their gut –> spread to other animals and humans
• Farm to table: drug resistance bacteria can remain on crops/animal meat –> consumed by humans