T2 - L5 ANTIBIOTIC RESISTANCE

Question 1

what are the 3 main causes of antibiotic resistance?

Answer 1

• mixture of sensitive and resistant bacterial strains exposed to antibiotics
• Subsequent endogenous infection more likely to be caused by antibiotic-resistant strains
• Antibiotic-resistant strains may be transferred to other people

Question 2

what is a innate resistance mechanism?

Answer 2

the bacteria is naturally resistant

Question 3

what is an acquired resistance?

Answer 3

bacteria has mutated to become resistant

Question 4

what innate resistance do gram-negative bacteria have?

Answer 4

are resistant to glycopeptides, daptomycin

NB: Gram – have an outer membrane impermeable to glycopeptides which act on the cell wall

Question 5

what are gram - bacteria resistant to glycopeptides?

Answer 5

Gram – have an outer membrane impermeable to glycopeptides which act on the cell wall

Question 6

what innate resistance do gram-positive bacteria have?

Answer 6

aztreonam, colistin

Question 7

what innate resistance do anaerobes have?

Answer 7

[are resistant to] aminoglycosides

NB: Anaerobes lacks the O2 dependent active transport required.

Question 8

what innate resistance do Streptococci have?

Answer 8

[are resistant to] aminoglycosides

Question 9

what is horizontal gene transfer?

Answer 9

transferring a gene from one organism to another

Question 10

how do mutations spread throughout bacteria themselves?

Answer 10

horizontal gene transfer

Question 11

what are the 5 mechanisms of resistance?

Answer 11

1. absent target
2. decreased permeability
3. target modification
4. enzymatic degradation
5. drug efflux

Question 12

why don’t β-lactam antibiotics work for fungi?

Answer 12

β-lactam affect peptidoglycan cell wall & fungi have β 1,3 glucan wall

Question 13

what cell wall do bacteria have?

Answer 13

peptidoglycan cell wall

Question 14

what cell wall do fungi have?

Answer 14

β 1,3 glucan wall

Question 15

what is a viral neuraminidase?

Answer 15

an enzyme found on the surface of influenza viruses that enables the virus to be released from host cell.

Question 16

where do you find neuraminidase?

Answer 16

surface of influenza viruses

Question 17

what do Neuraminidases cleave?

Answer 17

sialic acid groups from glycoproteins and are required for influenza virus replication

Question 18

what do antivirals target?

Answer 18

neuraminidases

Question 19

give 2 examples of antibiotic resistance that have occurred as a result of decreased permeability?

Answer 19

vancomycin (gram-negative bacilli)

gentamicin (anaerobic organisms)

Question 20

why do gram-negative bacilli have a resistance against vancomycin?

Answer 20

Gram-negatives have an outer membrane that is impermeable to vancomycin

Question 21

why are aerobic organisms resistant to gentamicin?

Answer 21

Uptake of aminoglycosides requires an O2 dependent active transport mechanism

Question 22

give 3 examples of antibiotic resistance that have arisen as a result of target modification?

Answer 22

flucloxacillin (MSRA)

Vancomycin (VRE)

Trimethoprim (gram-negative bacteria)

Question 23

what is meant by VRE?

Answer 23

Vancomycin-Resistant Enterococci

Question 24

what happens in MSRA?

Answer 24

MRSA is a staphylococcus aureus that is resistant to all β-lactams due to altered penicillin-binding protein (PBP2’, encoded by MecA gene) does not bind β-
lactams

Question 25

what gene does staphylococcus aureus have to carry to become resistant to flucloxacillin?

Answer 25

MecA gene

Question 26

what does the MecA gene code for?

Answer 26

- found in bacteria - codes for a altered penicillin binding protein - does not bind β- lactams as a result

Question 27

what mutation occurs for gram-negative bacilli to become resistant to trimethoprim?

Answer 27

Mutations in dhr (dihydrofolate reductase gene)

Question 28

list some enzymes produced by bacteria to degrade antibiotics.

Answer 28

β-lactamase Staphylococcal penicillinase Extended-spectrum β-lactamases (ESBL) Carbapenemases

Question 29

what enzyme degrades penicillin/amoxicillin?

Answer 29

Staphylococcal penicillinase

Question 30

what enzyme degrades chloramphenicol?

Answer 30

chloramphenicol acetyltransferase (CAT)

Question 31

explain the mechanism drug efflux?

Answer 31

- common resistance in fungi | - actively pumps antibiotic that enters the cell back out (imagine a revolving door)

Question 32

which fungi use the drug efflux mechanism?

Answer 32

Candida spp. against antifungal triazoles

Question 33

what 2 things enable horizontal transfer?

Answer 33

transposons integrons

Question 34

what are transposons and intergrons?

Answer 34

DNA sequences designed to be transferred from plasmid to | plasmid and/or from plasmid to chromosome

Question 35

what is a "cassette"?

Answer 35

A gene cassette is a type of mobile genetic element that contains a gene and a recombination site

Question 36

what is vertical transfer?

Answer 36

mother to daughter cells (as a result of binary fission)

Question 37

what is the difference between vertical and horizontal gene transfer?

Answer 37

vertical - from parent to daughter cells as a result of binary fission horizontal - from one grown organism to another grown organism via swapping plasmids (enabled by transposons and intergrons)

Question 38

what is meant by "antibiotic era"?

Answer 38

Term used to describe the time since the widespread availability of antibiotics to treat infection

Question 39

what is meant by "post-antibiotic era"?

Answer 39

Term used to describe the time after widespread antibiotic resistance has reduced the availability of antibiotics to treat infection

Question 40

which bacteria hasn't, and isn't likely to develop a resistance?

Answer 40

``` Strep pyogenes (Group A Strep) is and has always been sensitive to penicillin so no post antibiotic era ```

Question 41

what is meant by "empiric therapy"?

Answer 41

medical treatment or therapy based on experience

Question 42

testing antibiotic sensitivity on a agar plate, what does a large zone of inhibition indicate?

Answer 42

the more sensitive the organism to the antibiotic i.e. the | easier to be killed

Question 43

what is meant by the minimum inhibitory concentration (MIC)?

Answer 43

the minimum inhibitory concentration is the lowest concentration of a chemical, usually a drug, which prevents visible growth of bacterium.

Question 44

how would you monitor antimicrobial resistance?

Answer 44

- sensitivity testing (agar plate) | - liquid media (microtitre plate)

Question 45

why is sensitivity testing useful?

Answer 45

- to inform antibiotic therapy | - to provide epidemiological data "surveillance" (to inform local guidelines and antibiotic choices)