Mechanism of Resistance to Abs Flashcards

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1
Q

What is intrinsic resistance?

A

The innate ability of a bacterial species to resist activity of a particular antimicrobial agent through its inherent structural or functional characteristics
TOLERANCE to a particular drug/antimicrobial class

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2
Q

What is mutational resistance?

A

Antibiotic resistance due to chromosomal mutation
May be spontaneous or random
Depends on structure and number of genes in which mutations can produce a selectable phenotype

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3
Q

What is acquired resistance?

A

Occurs when a particular microorganism obtains the ability to resist the activity of a particular antimicrobial agent, to which it was previously susceptible to
Acquisition of a gene or genes conferring resistance through horizontal gene transfer or the process of swapping genetic material between neighboring bacteria

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4
Q

What are the three types of resistances? (IMA)

A

Intrinsic
Mutation
Acquired

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5
Q

Where can many Ab resistant genes be carried on?

A

Plasmids
Transposons
Integrons
All act as VECTORS

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6
Q

What do these vectors do?

A

Transfer the ab resistant genes to other members of the same bacteria as well as to diff types of bacteria

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7
Q

What are the three ways horizontal gene transfer can occur?

A

Transformation
Transduction
Conjugation

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8
Q

What does transformation involve?

A

Uptake of short fragments of naked DNA

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9
Q

What does transduction involve?

A

Transfer of DNA from one bacterium into another via bacteriophages (lytic/lysogenic)

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10
Q

What does conjugation involve?

A

Transfer of plasmids via sexual pilus and requires cell-cell contact

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11
Q

What are the mechanisms of Ab resistance? (7)

A
Enzymatic Inactivation
Decreased permeability
Efflux
Alteration of target gene
Protection of target gene
Overproduction of target
Bypass of inhibited process
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12
Q
  1. What are some some enzymes involved in Enzymatic Inactivation?
A

Beta-lactamses

  • Extended spectrum beta-lactamases (ESBLs)
  • Amp C Beta-lactamases
  • Carbapenemases
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13
Q

How do Beta-lactamases (penicillinases) cause enzymatic inactivation?

A

Resistance to Beta-lactam Abs occurs primarily through the production of Beta-lactamases.
Inactivate these Abs by splitting the amide bond of the Beta-lactam ring

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14
Q

Where do Beta-lactamases come from?

A

Encoded by either chromosomal genes
OR
By transferable genes located on plasmids and transposons
ADDITIONALY
B-lactamase genes (bla) freq reside on integrons
There are 4 classes (A-D)

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15
Q

How are additional class on the b-lactamses classified?

A

Based on the spectrum of activity w/ respect to the destruction of the beta lactam Abs

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16
Q

What are these additional b-lactamases?

A

Extended spectrum beta-lactamases (ESBLs)
Amp C Beta-lactamases
Carbapenemases

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17
Q

What are Extended spectrum beta-lactamases (ESBLs)?

A
They mediate resistance to EXTENDED-spectrum
-Cephalosporin
-Monobactams
NOT
-Cephamycins
-Carabapenems
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18
Q

What are Amp C Beta-lactamases (?

A

Chromosomal Enz that confer resistance to penicillins
some cephalasporins
oxymino-b-lactams
cephamycins

19
Q

What are Carbapenemases?

A

They confer the LARGEST Ab resistance spectrum
They hydrolyze not only carbapenems but ALSO
Penicillins
Oxymoni-cephalosporin
Cephamycins

20
Q

Where are ESBL usually found?

A

Klebsiellla
E. coli
Proteus

21
Q

How do you treat ESBLs producers?

A

Carbapenem

22
Q

Where are Amp C B-lactamases found?

A

Enterobacteriaceae (other than Klebsiella and E. coli)

23
Q

How do you overcome B-lactamase Enz?

A

Penicilllinase-resistant Penicillins
B-lactam Inhibitors and Inhibitor Combinations
Extended Spectrum Cephalosporins (3rd and 4th generations)
Carbapenams

24
Q

What are Penicilllinase-resistant Penicillins used to treat?

A

Penicillin resistant staphylococcus aures and straphylococcus epidermidis

25
Q

What are Penicilllinase-resistant Penicillins no affective for?

A

Enterococci

B-lactamse gram NEGATIVE bacteria

26
Q

What are B-lactam Inhibitors and Inhibitor Combinations used for?

A
They have weak Ab activity BUT
are POTENT inhibitors  of many class A Beta-lactamses
27
Q

How do B-lactam Inhibitors work?

A

They IRREVERSIBLY bind to the En (class A Beta-lactamases)

  • ->neutralize the En activity
  • ->prevent the hydrolysis of the Ab
  • ->restoring its activity
28
Q

How do Extended Spectrum Cephalosporins (3rd and 4th generations) work?

A

These are resistant to Beta-lactamses (but not ESBLs)

29
Q

How do carbapenems work?

A

Have a broad spectrum

HIGHLY resistant to most B-lactamases (including ESBLs)

30
Q

What usually occurs when using hydrophobic Abs?

A

They are enter through the outer mem, which is faciliatated by the presence of porins
Larger Abs=Less likely to penetrate through

31
Q
  1. What causes a decrease in the permeability of the bacterial membrane? (2)
A

Mutations resulting in the loss of specific porins
-increased resistance to B-lactam ABs
Lack of production of outer membranes
-Resistance to aminoglycosides and carbapenems

32
Q
  1. What is AB Efflux?
A

Its movement OUT of the cell

33
Q

What are some Abs that can be effluxed?

A

Tetracyclines
Macrolides and Streptogramins
B-lactams
Fluoroquinolines

34
Q
  1. How are target sites altered?
A

Alteration of ribosomal binding sites

  • ->prevent Ab from binding to target site
  • ->disrupt ability to inhibit protein synthesis and cell growths
35
Q
  1. How are target sites protected? And thus cause Ab resistance?
A

Tetracycloines : By mechanisms that interference with the ability of tetracycline to bind to ribosome

Fluroquinolones: A gene protect DNA gyrase from binding to quinolones
–>allowing the bacterium to resist quinolone inhibitorty effects

36
Q
  1. How does overproduction of a target cause Ab resistance?
A

Sulfonamides and Trimethropin: overproduction of either DHPS or DHFR (synthetic En’s)
–>Abs bind to the synthetic En rather than the real target
Vancomycin-intermediate S. aureus - expressed THICK pep cell walls (over production of D-alanine-D-alanine precursor molecules)
–>Vancomycin molecules absorbed by these excess binding sites (prevent it from reaching its target site)

37
Q

How do altered metabolic PW’s cause AB resistance?

A

Developing alternate metabolic PWs

38
Q

How do alterations of the cell wall precursor target sites cause Ab resistance?

A

Vancomycin/Glycopeptide Abs bind to the d-alanine-d-alanine (present at the termini of peptidoglycan presursors)
Alteration of the d-ala-d-ala –> d-ala-d-LAC
–>prevents vancomycin from binding
–>resistance

39
Q

How do alterations of the target enzyme cause Ab resistance?

A

Through MODIFIED penicillin binding proteins

40
Q

How do penicillin binding proteins usually work?

A

Normally B-lactam Abs INHIBIT bacteria by BINDING covalently to PBP (penicillin binding proteins aka transpeptidases) in the cytoplasmic mem

41
Q

What are these PBP proteins for?

A

They catalyze the synthesis of the pep that forms the cell wall of the bacteria

42
Q

What do MPBPs do?

A

They are alterations of the PBP that prevent B-lactam Abs from binding
–>Ab resistance

43
Q

About MRSA and its alteration of PBP (target En)

A

Is S. aureus

Methicillin resistant caused by the expression of the mecA gene–>encodes PBP2a

44
Q

What does PBP2a do?

A

It is a protein with low affinity for b-lactam Abs (including the inhibitors)
–>resistance to ALL b-lactam Abs/inhibitors