Antibiotic Resistance Flashcards

1
Q

Where did most antibiotic resistance most likely emerge from

A

overuse of antibiotics in agriculture

misuse of antibiotics in humans: 50% inappropriate use, wrong dosage or duration such as in a viral infection

there are 25 million pounds of non therapeutic livestock use and there are about 3 million pounds of human medical use

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2
Q

What does MDR stand for

A

multidrug resistant

resistant to three or more antibiotic categories

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3
Q

How many antibiotics are MDR (multi drug resistant) bacteria resistant to

A

resistant to three or more antibiotic categories

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4
Q

What does XDR stand for

A

extensively drug resistant

susceptible to two or fewer antibiotic categories

only two or one antibiotic category would work

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5
Q

What does PDR stand for

A

pan drug resistant

not susceptible to any of the approved drugs in all categories

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6
Q

How many antibiotics are XDR (extensively drug resistant) bacteria resistant to

A

only susceptible to two or fewer antibiotic categories

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7
Q

How many antibiotics are PDR (pan drug resistant) bacteria resistant to

A

not susceptible to any of the approved drugs in all categories

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8
Q

There are the 6 well known multi drug resistant pathogens

A

Enterococcus spp. VRE

Staphylococcus aureus MRSA

Klebsiella spp. CRE

Acinetobacter baumannii ESBL

Pseudomonas aeruginosa ESBL

Enterobacter spp. CRE

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9
Q

What are the main mechanisms of antibiotic resistance

A
  1. restriction of the antibiotic to the antibiotic target
  2. enzymatic inactivation of the antibiotic
  3. modifying the antibiotic target
  4. protecting the antibiotic target
  5. failure to activate the antibiotic
  6. restriction of access to target: outermsmbrane barrier, selective porins, efflux pumps
  7. enzymatic inactivation: beta-lactamase, aminoglycoside modifying enzymes, CAT
  8. target modification or protection: PBPs with reduced affinity for beta lactase, point mutations that alter affinity of DNA gyrase to fluoroquinolone, RNA polymerase mutations alter affinity to rifampin, 23S rRNA mthylases, D-ala-D-lac substations
  9. failure to activate the antibiotic: metronidazole is a prodrug requiring reduction by bacterial flavodoxin to active form, reduced expression to flavodoxin
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10
Q

What are examples of restriction of the antibiotic to the antibiotic target

A

outer membrane barrier

selective porins

efflux pumps

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11
Q

What are examples of enzymatic inactivation of the antibiotic

A

beta-lactamase

aminoglycoside modifying enzymes

CAT

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12
Q

How do outer membrane porins work against antibiotics

A

outer membrane: formidable barrier

outer membrane porins are selective gatekeepers

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13
Q

How do outer membrane porins work against antibiotics

A

outer membrane: formidable barrier

outer membrane porins are selective gatekeepers

small molecules can diffuse to periplasm through porins

antibiotics such as vancomycin and daptomycin are too large to get through porins and the outer membrane

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14
Q

What types of antibiotics do porins prevent/ how does this process work/ what type of antibiotic resistance is this

A

vancomycin and daptomycin are too large to diffuse through the periplasm through porins

usually small molecules diffuse through porins into the periplasm

restriction of access of the antibiotic to its target

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15
Q

How do antibiotic efflux pumps work against antibiotics

A

efflux pumps have been discovered for nearly every class of antibiotic

gram - efflux pumps span both membranes and is analogous to type I secretion system

gram + efflux pumps are simple anti-porters or ABC transporters

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16
Q

What type of efflux pump do gram - bacteria have

A

span both membranes and is analogous to type I secretion system

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17
Q

What type of efflux pump do gram + bacteria have

A

are simple anti-porters or ABC transporters

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18
Q

An efflux pump is a type of ____ antibiotic resistance mechanism

A

restriction to access of the antibiotic to its target

19
Q

How do serine beta-lactamases work against antibiotics

A

cleave the beta-lactam ring of antibiotics

similar mechanism to the beta lactams action on the transpeptidase enzyme

20
Q

Are serine beta-lactamases more common in gram - or gram +

A

more common in gram negative bacteria

21
Q

How do zinc beta-lactamases work against antibiotics

A

cleave the antibiotic at a different site

clavulanic acid and other inhibitors cannot interact with the zinc form

can cleave a wider range of beta lactams than serine beta-lactamases

used against Carbapenems: Doripenem, Meropenem, Imipenem

22
Q

What does clavulanic acid do

A

inactivates beta-lactamase in when added with SERINE beta-lactamases used with penicillin, cephalosporins: Ceftazidime, Cefotaxime, Ceftriaxone???

clavulanic acid and other inhibitors cannot interact with the ZINC form

23
Q

When is clavulanic acid usually administered with

A

beta lactams can be administered in combination with a beta lactase inhibitor bc the clavulanic acid inactivates beta lactamases in SERINE beta lactamases

clavulanic acid and other inhibitors cannot interact with the ZINC form

24
Q

What type of antibiotic resistance mechanism do serine beta lactamases and zinc beta lactamases

A

enzymatic inactivation

25
Q

What type of antibiotic resistance mechanism is aminoglycosides

A

enzymatic inactivation

inactivated by the addition of modifying groups

modifications disrupt interaction of the antibiotic with its cellular target (30S ribosome via 16S rRNA)

26
Q

How do aminoglycosides work against antibiotics, what antibiotics are most likely to be inactivated against this

A

inactivated by the addition of modifying groups

modifications disrupt interaction of the antibiotic with its cellular target (30S ribosome via 16S rRNA)

Kanamycin and Gentamycin

27
Q

What type of antibiotic resistance mechanism is the penicillin-binding protein resistance in bacteria

A

target modification

28
Q

How does the penicillin-binding protein resist against antibiotics what type of antibiotics are most susceptible, what type of bacteria uses this

A

modification prevents binding of beta lactase ring

involves modification of existing amino acids

clavulanic acid cannot block this type of resistance

common in gram + bacteria MRSA/VRE

mutations in penA gene confers resistance of PBP to Cephalosporins in N-gonorrhoeae

mutations in mecA gene codes for novel PBP with reduced affinity for beta lactams

29
Q

What type of antibiotic resistance mechanism is vancomycin resistance in bacteria

A

target modification

30
Q

How does vancomycin resist against antibiotics what type of antibiotics are most susceptible, what type of bacteria uses this

A

conjugative transposons/plasmids

the antibiotic normally prevents the peptide inter bridge from forming, by binding strongly to D-ala-D-ala residues in the stem peptide

this prevents the transpeptidase from linking the cross-bridge

modifys D-ala-D-ala to D-ala-D-lac

vancomycin binds D-ala-D-lac 1000 times less effective than D-ala-D-ala which explains resistance

31
Q

What type of antibiotic resistance mechanism is macrolide resistance in bacteria

A

target modification

32
Q

How does macrolide resistance work

A

RNA methylates can add methyl groups to reside A2058 in the 23S RNA target site of the ribosome

the antibiotic can no longer bind to the large subunit and block the polypeptide exit

33
Q

What type of antibiotic resistance mechanism is used by TetO, TetM, and TetQ mediating tetracycline resistance

A

ribosomes protection by TetO, TetM, and TetQ that mediate tetracycline resistance

target protection

34
Q

How does TetO, TetM, and TetQ mediating tetracycline resistance work

A

ribosomes protection by TetO, TetM, and TetQ that mediate tetracycline resistance

addition to efflux based

35
Q

How does TetO, TetM, and TetQ mediating tetracycline resistance work

A

ribosomes protection by TetO, TetM, and TetQ that mediate tetracycline resistance

in addition to efflux based systems that clear tetracycline from the cell

a new modified version of tetracycline called glycylglycines overcome these resistance mechanisms

36
Q

What type of tetracycline can overcome tetracycline resistance

A

glycylglycines

37
Q

What type of antibiotic resistance mechanism is used by metronidazole resistance

A

failure to activate

38
Q

How does metronidazole resistance work

A

failure to activate the antibiotic

activated by flavodoxin

damages DNA by causing nicks

no active form: no nick: no drug sensitivity

flavodoxin reduces the nitro group on the inactive from of metronidazole and this changes the active form and H. pylori decreases the expression of flavodoxin which decreases the active from expression

39
Q

How are H.pylori resistant to antibiotics

A

metronidazole resistance

metronidazole is activated by flavodoxin which damages DNA and causes nicks

flavodoxin reduces the nitro group on the inactive from of metronidazole and this changes the active form and H. pylori decreases the expression of flavodoxin which decreases the active from expression

no active form: no nick: no drug sensitivity

failure to activate

40
Q

How does isoniazid resistance work

A

Isoniazid is activated by KatG (catalase), Isoniazid blocks mycotic acid synthesis

no active form, no inhibition of cell wall, no drug sensitivity

resistance stems from altered expression or function of KatG

41
Q

What type of antibiotic resistance mechanism is used by isoniazid resistance

A

failure to activate the antibiotic

42
Q

What is the genetic linkage between multi drug resistance bacteria

A

some plasmids contain independent genes involved in antibiotic resistance

43
Q

What are persisters and how do they lead to persistent

A
  1. bulk population that an antibiotic is added to
  2. some persisters are a small sub population of cells that temporarily stop dividing and then the antibiotic is removed
  3. there is a repopulation of bacteria and then the an antibiotic is added again
  4. the majority of bacteria die but some persisters remain