The Importance of Cell Biology & AMR (antimicrobial resistance)

Question 1

Outline the importance of microbiology in veterinary science

Answer 1

It has a daily impact:
-Prevention (vaccinations, probiotics, owner education)
-Treatment (diarrhoea, skin infections, bite wounds)
-Sterilisation of instruments
-Biosecurity
-Epidemiology
-Antimicrobial Stewardship

Understanding disease processes

Antimicrobial Resistance

Question 2

Describe the concept of antimicrobial stewardship

Answer 2

The actions veterinarians take individually and as a profession to preserve the effectiveness and availability of anti -microbial drugs through conscientious oversight and responsible medical decision-making, whilst safeguarding animal, public & environmental health

Question 3

Outline what is meant by antimicrobial resistance

Answer 3

Multi-resistance mechanisms often carried on mobile genetic elements – rapid spread within and between bacterial species

It is naturally occurring and widespread within the environment

Question 4

List drug targets for antibiotics

Answer 4

Cell wall synthesis
Cell membrane
Nucleic Acid synthesis
Protein Synthesis

Question 5

How is the cell wall targeted by antibiotics?

Answer 5

Contains components unique to bacteria

Penicillin (β-lactam)
-Inhibits enzymes involved in forming the cross links between the peptidoglycans

Other Antibiotics:
-Ampicillin (β-lactam)
-Vancomycin (glycopeptide)

β-lactams inhibit transpeptidation by binding to penicillin-binding proteins (PBPs) on maturing peptidoglycan strands leading to decrease in peptidoglycan and promoting autolysin activity

Bactericidal

Question 6

How is the cell membrane targeted by antibiotics?

Answer 6

Disrupted functional integrity of cell membrane leads to escape of macromolecules & ions from bacterial cell (lysis)

Antibiotics
-Polymyxin
-Colistin
Both target outer mebrane of gram negative bacteria

Bactericidal

Question 7

What are the disadvantages to cell membrane targeted antibiotics?

Answer 7

Due to large similarities between animal and bacteria cell membranes, the drugs have an increased toxicity for animal cells.

Drugs are often used as a last resort in human medicine

Question 8

How is protein synthesis targeted by antibiotics?

Answer 8

Difference in ribosome structure between eukaryotes (80 S ribosomes) & prokaryotes (70 S ribosomes)

-Tetracycline
Blocks tRNA molecules attachment site on 30 S sub unit

-Erythromycin
-Chloramphenicol
Both block 50 S sub unit preventing growth of polypeptide chain

-Aminoglycosides
Bind to 30 S sub unit inhibiting proof reading and initiation

Bacteriostatic

Question 9

How is nucleic acid synthesis targeted by antibiotics?

Answer 9

Organisation and replication of bacterial DNA & RNA is different to eukaryotes

-Quinolones (Nalidixic acid)
-Novobiocin
Both act on DNA Gyrase (enzyme which separates DNA strands during bacterial
replication). They do this by binding to topoisomerase II or topoisomerase IV
-Rifampin
Interferes with DNA-dependent RNA polymerase activity so preventing RNA
synthesis

Bacteriostatic

Question 10

Describe how bacteria of different groups can have different antibiotic resistances

Answer 10

Enzymes that degrade or inactivate antibiotic
B-lactamases - enzymes which degrade or inactivate antibiotic

	Example of Antibiotic affected: penicillin/ ampicillin

Alteration of target site
Altered ribosome structure - alter target site (common with antibiotics whihc work
on ribosome structure)

	Example of Antibiotic affected: erythromycin

Elimination of antibiotic from bacterial cell
Efflux Pump - rid the antibiotic out of the cell through this pump (expensive for
bacteria)
Conc of antibiotic in environment doesn’t change so bacteria will continually have to
pump

	Example of Antibiotic affected: tetracycline

Bacterial cell impermeable for antibiotic
Gram negative cell wall - inherently resistant

	Example of Antibiotic affected: penicillin

Question 11

Rationally define the microbial disease process (Infection)

Answer 11

Invasion and / or colonisation by subsequent multiplication of pathogens in bodily part or tissue

Which can produce subsequent tissue injury

And progression to overt disease through a variety of cellular or toxic mechanisms

Question 12

Rationally define the microbial disease process (Causation of disease)

Answer 12

Infection

Produce toxins
Often with infection but can be ingestion of preformed toxin

Host response
Allergic reaction

Question 13

Outline Koch’s Postulates (1984) to define a pathogen

Answer 13

1. The organism must be found in all animals suffering from the disease, but not in healthy animals.
2. The organism must be isolated from a diseased animal and grown in pure culture.
3. The cultured organism should cause disease when introduced into a healthy animal.
4. The organism must be re-isolated from the experimentally infected animal.

Koch abandoned the second part of the first postulate altogether when asymptomatic carriers of cholera were discovered (Koch, 1893).

Question 14

What is the terminology used when describing pathogen prevalence?

Answer 14

Sporadic
Diseases popping up here and there
Enzootic
Regularly affecting animals in a particular district or at a particular season.

Endemic
Term that relates to humans - regularly found among particular group people
or in a certain area. However, endemic is often used as a veterinary term.

Question 15

What does latency mean?

Answer 15

Pathogen goes inert within the aniaml. Can be reactivated

Question 16

What does carriage mean?

Answer 16

Animal tolerates pathogen without disease but is capable of transmitting the organism

Question 17

What is meant by reservoir of infection?

Answer 17

Any animal, human, environment in which the infectious agent normally lives & multiplies

Question 18

Describe the differences between eukaryotic and prokaryotic cells

Answer 18

Differences between eukaryotic and prokaryotic cells include

Cell wall synthesis

Cell membrane structure & function

DNA synthesis

Transcription

Translation / protein synthesis