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D&D Unit 3 > Mechanisms of Antibiotic Resistance (complete) > Flashcards

Mechanisms of Antibiotic Resistance (complete) Flashcards

1
Q

What is intrinsic resistance?

A
  • The bug just happens to be resistant
  • Was this way before antibiotics were even invented

Pseudomonas is a great example

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2
Q

What is acquired resistance?

A
  • It’s acquired! No shit sherlock
  • Developed through mutations, new genes — bacteria can figure shit out

Important: resistance is a multi-step process and most bacteria will not be resistant after one mutation — but they will with a new gene

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3
Q

What are the broad categories of antibiotic resistance?

A

1) Inactivate/modify drug
2) Alter the antibacterial target
3) Reduce the ability of the drug to reach the target

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4
Q

How do porins mediate antibiotic resistance? For which bacteria is this important?

A
  • Porins found in g(-) bacteria (they have an outer membrane)
  • Antibiotic must go through the channel to its job
  • Bacteria alter structure of porin channels to resist teh antibiotic
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5
Q

How do efflux pumps mediate antibiotic resistance? For which bacteria is this important?

A
  • Found in g(+) and g(-)
  • Can be specific or general (either cause 1 antibiotic to be pumped out of cell or more)
  • Can prevent antibiotic from doing its thang — can’t alter whatever it’s designed to alter in the cell
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6
Q

Describe the structure and building of peptidoglycan as it relates to the mechanisms of activity of beta-lactams and vancomycin.

A

Structure: backbone of 2 alternating sugars, cross-linked

Formation: adding precursors —» cross-linking then driven by cleavage of terminal stem-peptide AAs (enzymes involved here are called PBPs)

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7
Q

Describe how changes in peptidoglycan synthesis may result in resistance to these agents

A
  • Some antibiotics target specific steps in peptidoglycan synthesis
  • Overall prevents cell wall synthesis of bacteria
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8
Q

Describe how beta-lactams work

A
  • Bind to and inactivated PBPs
  • it’s irreversible
  • Prevents peptidoglycan formation

THINK: Stage 3!!!

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9
Q

Describe how bacteria become resistant to beta-lactams

A

1) Modify drug => w/ beta-lactamases
2) Modify target => alter PBPs

Example of altered PBPs: MRSA

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10
Q

Describe the spectrum of activity of “narrow spectrum” beta-lactamases.

A
  • Hydrolyze PCN-type antibiotics
  • Not much activity against cephalosporins
  • Found in g(+) and g(-) bacteria
  • Encoded on chromosome or a plasmid!
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11
Q

Which bacteria house “narrow spectrum” beta-lactamases?

A

1) S. aureus (resistant to PCNs, ampicillin) => plasmid
2) E. Coli TEM1 (amp) => plasmid
3) Klebsiella (amp) => chromosome

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12
Q

Describe the spectrum of activity for ESBLs

A
  • Extended Spectrum Beta-Lactamases
  • Almost all found on plasmids (highly mobile)
  • Found in g(-) rods
  • Resistant to PCNs and most cephalosporins (aka that’s why it’s EXTENDED)
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13
Q

Which bacteria house ESBLs?

A
  • Mutants of TEM1, TEM2, SHV1

- E.coli and Klebs. pneumo love to pick up the plasmids w/ these point mutations

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14
Q

Describe the spectrum of activity for ampC?

A
  • Found in the chromosomes! — inducible or on allll the time
  • in certain g(-) rods
  • Resistance to PCNs and cephalosporins
  • CANNOT be inhibited by beta-lactamase inhibitors (e.g. tazobactams)
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15
Q

Which bacteria house ampC?

A
  • Pseudomonas

- Enterobacter

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16
Q

Describe the spectrum of activity for carbapenemases.

A
  • Developed b/c everyone was usually carbapenems to treat ampC and ESBL bacteria (b/c of resistance to other drugs)
  • Resistant to all beta-lactams
  • Found on plasmids
17
Q

Which bacteria house carbapenemases?

A
  • KPC: Kleb pneumo carbapenemase

- NDM-1: New Delhi metallo-beta-lactamase

18
Q

Describe the regulation of ampC expression

A
  • Expression is the key part of AmpC
  • Normally => low level of expression, but induced by specific beta-lactamas
  • Therapy causes it to switch from inducible to constitutive (on all the time)
  • Mutation causes inducer to be present all the time as a leftover part of peptidoglycan formation
19
Q

What are the different ways that PBPs may be altered that lead to beta-lactam resistance?

A
  • Mutation of existing genes
  • Acquiring new PBP genes
  • Acquiring new pieces of PBP genes
20
Q

Which bacteria house altered PBPs?

A
  • Staph species (s. aureus, MRSA) — new gene
  • Strep pneumo — new pieces
  • N. gonnhoroeae — new pieces
21
Q

How does Vancomycin work?

A
  • Targets peptidoglycan precursor => binds to D-ala-D-ala
  • Inhibits incorporation of precursor w/ PD => disrupts CW synthesis

THINK: STAGE 2

22
Q

How do bacteria become resistant to Vancomycin?

A
  • G(-) rods intrinsically resistant
  • Modifying the target (changes the D-ala-D-ala –» D-ala-D-lactate)
  • Seen in enterococcus
23
Q

Describe the mechanisms of resistance to macrolides

A
  • Macrolides target RNA => prevent peptide elongation

Resistance mechanisms:

  • Modify target => erm gene (changes, dimethylates ribosome)
  • Prevent drug-target interaction => drug efflux, msr gene
  • S. aureus can become resistant to Erythromycin in these ways
24
Q

Describe the mechanisms of resistance to aminoglycosides

A
  • Modifies the drug: acetylation, nucleotidylation, phosphorylation
  • Get an enzyme that does one of the above
25
Q

Describe the mechanisms of resistance to quinolones

A
  • Target DNA gyrase/topoisomerase IV => lethal DNA strand breaks

Resistance:
- Modify target: accumulate many point mutations in those enzymes

26
Q

Describe the mechanism of erm-mediated resistance

A
  • Can be inducible or on all the time (macrolides do this)

- While on therapy, you can develop a mutation that shifts from inducible to on all the time

27
Q

How is the mechanism of erm-mediated resistance related to clindamycin resistance?

A
  • Clindamycin can cause a switch fro inducible to constitutive
  • Clindamycin is sensitive to inducible erm but obviously not to constitutive erm
  • Used to determine method of resistance of specific staphs
28
Q

What is the utility of the D-test as it relates to the mechanism of erm-mediated resistance?

A
  • Done when you’re resistant to erythromycin and sensitive to clindamycin
  • If D-test is positive (have inducible erm), you don’t want to use clindomycin or erythromycin
  • If negative (efflux pump present), then you can use clindamycin, still no macrolides (erythromycin)
29
Q

Why is E. Coli naturally resistant to penicillin but sensitive to ampicillin?

A

Porins!

30
Q

Why is mycoplasma resistant to all beta-lactams?

A

No cell wall!

31
Q

What are 2 types of bacteria that are similar to E. Coli? What type of bacteria are they?

A

1) Enterobacter
2) Klebsiella

G(-) rods

32
Q

How does strep pneumo become resistant to beta-lactams?

A
  • Through an altered PBPs

IMPORTANT:
NO STREPS HAVE BETA-LACTAMASES!!!!!

D&D Unit 3 (12 decks)

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