Infection - Bacterial Resistance Flashcards

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1
Q

Intrinsic Resistance

A

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

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2
Q

What are the types of intrinsic resistance?

A

Efflux Pumps
Altered Target Sites
Impermeable Cell Walls
Alternate Metabolic pathways

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3
Q

How do Efflux Pumps work?

A

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

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4
Q

What is an example of altering target cites?

A

PBP mutations reduce beta-lactam affinity

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5
Q

What is an example of protein synthesis drug resistance?

A

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

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6
Q

What is the mechanism of Beta-Lactams?

A

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

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7
Q

What is an example of alternate metabolic pathways?

A

Folic Acid biosynthesis important for NT productions

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8
Q

What antibiotics inhibit Folic Acid biosynthesis enzymes?

A

Sulfonamide and Trimethoprim inhibit dihydropteroate synthase and dihydrofolate redcutase respectively.

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9
Q

How is Folic Acid inhbitance bypassed?

A

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

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10
Q

What is intrinsic resistance independent of?

A

Previous antibiotic exposure and horizontal gene transfer.

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11
Q

Minimum Inhibitory Concentration

A

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

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12
Q

How is MIC tested?

A

Broth Diffusion Method
Kirky-Bauer Disk Diffusion Test

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13
Q

How is the Broth Diffusion Method performed?

A

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

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14
Q

How is the Kirby-Bauer Disk Diffusion Test performed?

A

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.

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15
Q

Why is MIC important?

A

Tracking of bacterial population susceptibility and tracking AM resistance?

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16
Q

Acquired Resistance

A

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

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17
Q

What are the three primary mechanisms of acuired resistance?

A

Horizontal gene transfe, mutaiton and selective pressure

18
Q

Horizontal Gene Trasnfer

A

This is reproduction of genetic material independent of organism reproduction

19
Q

What are the three types of horizontal gene transfer?

A

Transformaiton
Transduction
Conjugation

20
Q

Transformaiton

A

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

21
Q

Transduction

A

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

22
Q

Conjugation

A

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

23
Q

What is an example of mycobacteria drug uptake limitation?

A

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

24
Q

How do mycobacterial porins assist in resistance?

A

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

25
Q

What is an example of a mycobaterial resistance?

A

Tuberculosis response to isoniazid decreases cyclopropane containing mycolic acids decreasing permeability

26
Q

How is isoniazid activated?

A

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

27
Q

How might bacteria modify drug targets?

A

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

28
Q

What is an example of drug target alteration?

A

Aminoglycoside-modifying enzymes chemically modify aminoglycoside antibiotics

29
Q

Aminoglycoside Antibiotics

A

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

30
Q

What are mechanisms of drug target alteration?

A

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

31
Q

What is the base strucutrre of B-Lactams?

A

Beta Lactam Ring

32
Q

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

A

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

33
Q

What is the structre of the b-lactam ring?

A

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

34
Q

What is the mechanism of action of B-Lactams?

A

Inhibitio nof PBP in pg cell wall synthesis

35
Q

How does the carbonyl and serine interact?

A

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

36
Q

What do B-Lactams mimic?

A

D-Alanine poriton of the PG precursor.

37
Q

What is an example of resistance to B-Lactams?

A

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

38
Q

What is the most common form of acquired resistance?

A

Plasmid acquistion taken up by outside material

39
Q

What is the mutation rate of bacteria?

A

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

40
Q

How might biofilm protect against drug activity?

A

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

41
Q

Vancomycin

A

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