Infection - Bacterial Resistance

Question 1

Intrinsic Resistance

Answer 1

This describes bacterial resistance to an antibiotic without acquisition of external factors, so inherent to them

Question 2

What are the types of intrinsic resistance?

Answer 2

Efflux Pumps
Altered Target Sites
Impermeable Cell Walls
Alternate Metabolic pathways

Question 3

How do Efflux Pumps work?

Answer 3

Substrates bind with conformational changes allowing its transport across the cell membrane, coupled with ATP hydrolysis.

Question 4

What is an example of altering target cites?

Answer 4

PBP mutations reduce beta-lactam affinity

Question 5

What is an example of protein synthesis drug resistance?

Answer 5

S.aureus mutations in 23s rRNA reduce affinity for arythromycin

Question 6

What is the mechanism of Beta-Lactams?

Answer 6

Covalent linkage with the serine residue of the active site of PBP otherwise required as a nucleophile for cross-linkage.

Question 7

What is an example of alternate metabolic pathways?

Answer 7

Folic Acid biosynthesis important for NT productions

Question 8

What antibiotics inhibit Folic Acid biosynthesis enzymes?

Answer 8

Sulfonamide and Trimethoprim inhibit dihydropteroate synthase and dihydrofolate redcutase respectively.

Question 9

How is Folic Acid inhbitance bypassed?

Answer 9

Absorption of envionrmnetal folate converting pre-formed folate into active tetrahydrofolate.

Question 10

What is intrinsic resistance independent of?

Answer 10

Previous antibiotic exposure and horizontal gene transfer.

Question 11

Minimum Inhibitory Concentration

Answer 11

This is the minimum concentration of antibiotics required that can completely inhibit growth of a microorganism

Question 12

How is MIC tested?

Answer 12

Broth Diffusion Method
Kirky-Bauer Disk Diffusion Test

Question 13

How is the Broth Diffusion Method performed?

Answer 13

Taking a series of tubes with increasing concentrations of the antibiotics then inoculating with test organism: incubated then MIC determined by lowest concentration awt which agent inhibits growth completelte

Question 14

How is the Kirby-Bauer Disk Diffusion Test performed?

Answer 14

This takes a paper disk with the antimicrobial agent placed on surface of an agar plate incoulated with organism, plate incubated with zone of inhibition emasured.

Question 15

Why is MIC important?

Answer 15

Tracking of bacterial population susceptibility and tracking AM resistance?

Question 16

Acquired Resistance

Answer 16

This is the resistance of agents by genetic hcanges or genetic element acquisiton.

Question 17

What are the three primary mechanisms of acuired resistance?

Answer 17

Horizontal gene transfe, mutaiton and selective pressure

Question 18

Horizontal Gene Trasnfer

Answer 18

This is reproduction of genetic material independent of organism reproduction

Question 19

What are the three types of horizontal gene transfer?

Answer 19

Transformaiton
Transduction
Conjugation

Question 20

Transformaiton

Answer 20

THis is the uptake of DNA by recognition of surface receptors, faciltiated by competence factors

Question 21

Transduction

Answer 21

This is the transfer of genetic material through bacterioophages that integrate into the genome

Question 22

Conjugation

Answer 22

This is the trasnfer of plasmids between bacterial cells, often by plasmids carrying antibiotic resistance.

Question 23

What is an example of mycobacteria drug uptake limitation?

Answer 23

Alteration of high hydrophobic nature using long-chain mycolic acids.

Question 24

How do mycobacterial porins assist in resistance?

Answer 24

Ther are narrower in diameter than GNB with capacity to selectively exude hydrophilic molecules.

Question 25

What is an example of a mycobaterial resistance?

Answer 25

Tuberculosis response to isoniazid decreases cyclopropane containing mycolic acids decreasing permeability

Question 26

How is isoniazid activated?

Answer 26

Catalase-peroxidase which produces a reactive species altering the bacterial cell wall

Question 27

How might bacteria modify drug targets?

Answer 27

Genetic mutations of the targets of the drug or enzymes that degrade them

Question 28

What is an example of drug target alteration?

Answer 28

Aminoglycoside-modifying enzymes chemically modify aminoglycoside antibiotics

Question 29

Aminoglycoside Antibiotics

Answer 29

This is a group of drugs used to treat infections by aerobic GNB

Question 30

What are mechanisms of drug target alteration?

Answer 30

Plasmids/Transposons encoding acetyltransferases enzymes to NH3 or OH of antibiotic reducing affinit. Over-expression of target molecule to saturate bacteria.

Question 31

What is the base strucutrre of B-Lactams?

Answer 31

Beta Lactam Ring

Question 32

What are examples of the differences of beta lactam ring structure?

Answer 32

Cephalosporins have a dihydrothiazine ring fused to the b-lactam ring Carbapenems have a five-membered ring fused to a b-lactam ring

Question 33

What is the structre of the b-lactam ring?

Answer 33

Four memebred ring containing an amide group and a carbonyl group, both being polar

Question 34

What is the mechanism of action of B-Lactams?

Answer 34

Inhibitio nof PBP in pg cell wall synthesis

Question 35

How does the carbonyl and serine interact?

Answer 35

Serine partial positive whilst carbonyl partially negative, forming a covalent bond stabilised by h-bonding of amide group to AA residues in active site.

Question 36

What do B-Lactams mimic?

Answer 36

D-Alanine poriton of the PG precursor.

Question 37

What is an example of resistance to B-Lactams?

Answer 37

Methicillin-Resistant Staphylococcus Auresus through PBP2a gene with lower affinity to beta-lactams through mecA gene acquitisiiton.

Question 38

What is the most common form of acquired resistance?

Answer 38

Plasmid acquistion taken up by outside material

Question 39

What is the mutation rate of bacteria?

Answer 39

about 1 of every 10^6 to 10^9 per nucleotide per cell divisions.

Question 40

How might biofilm protect against drug activity?

Answer 40

Due to being sessile thus minimal metabolic activity/PBP to activate.

Question 41

Vancomycin

Answer 41

An AB inhibiting cell wall formation as an alternative for people allergic to penicillin.