Mechanism of Resistance to Abs Flashcards by Stephanie Cortes

What is intrinsic resistance?

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

How well did you know this?

Not at all

Perfectly

What is mutational resistance?

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

How well did you know this?

Not at all

Perfectly

What is acquired resistance?

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

How well did you know this?

Not at all

Perfectly

What are the three types of resistances? (IMA)

Intrinsic
Mutation
Acquired

How well did you know this?

Not at all

Perfectly

Where can many Ab resistant genes be carried on?

Plasmids
Transposons
Integrons
All act as VECTORS

How well did you know this?

Not at all

Perfectly

What do these vectors do?

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

How well did you know this?

Not at all

Perfectly

What are the three ways horizontal gene transfer can occur?

Transformation
Transduction
Conjugation

How well did you know this?

Not at all

Perfectly

What does transformation involve?

Uptake of short fragments of naked DNA

How well did you know this?

Not at all

Perfectly

What does transduction involve?

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

How well did you know this?

Not at all

Perfectly

What does conjugation involve?

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

How well did you know this?

Not at all

Perfectly

What are the mechanisms of Ab resistance? (7)

Enzymatic Inactivation
Decreased permeability
Efflux
Alteration of target gene
Protection of target gene
Overproduction of target
Bypass of inhibited process

How well did you know this?

Not at all

Perfectly

What are some some enzymes involved in Enzymatic Inactivation?

Beta-lactamses

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

Where do Beta-lactamases come from?

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)

How well did you know this?

Not at all

Perfectly

How are additional class on the b-lactamses classified?

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

How well did you know this?

Not at all

Perfectly

What are these additional b-lactamases?

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

How well did you know this?

Not at all

Perfectly

What are Extended spectrum beta-lactamases (ESBLs)?

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

How well did you know this?

Not at all

Perfectly

What are Amp C Beta-lactamases (?

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

What are Carbapenemases?

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

Where are ESBL usually found?

Klebsiellla
E. coli
Proteus

How do you treat ESBLs producers?

Carbapenem

Where are Amp C B-lactamases found?

Enterobacteriaceae (other than Klebsiella and E. coli)

How do you overcome B-lactamase Enz?

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

What are Penicilllinase-resistant Penicillins used to treat?

Penicillin resistant staphylococcus aures and straphylococcus epidermidis

What are Penicilllinase-resistant Penicillins no affective for?

Enterococci | B-lactamse gram NEGATIVE bacteria

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

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

How do B-lactam Inhibitors work?

They IRREVERSIBLY bind to the En (class A Beta-lactamases) - ->neutralize the En activity - ->prevent the hydrolysis of the Ab - ->restoring its activity

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

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

How do carbapenems work?

Have a broad spectrum | HIGHLY resistant to most B-lactamases (including ESBLs)

What usually occurs when using hydrophobic Abs?

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

2. What causes a decrease in the permeability of the bacterial membrane? (2)

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

3. What is AB Efflux?

Its movement OUT of the cell

What are some Abs that can be effluxed?

Tetracyclines Macrolides and Streptogramins B-lactams Fluoroquinolines

4. How are target sites altered?

Alteration of ribosomal binding sites - ->prevent Ab from binding to target site - ->disrupt ability to inhibit protein synthesis and cell growths

5. How are target sites protected? And thus cause Ab resistance?

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

6. How does overproduction of a target cause Ab resistance?

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)

How do altered metabolic PW's cause AB resistance?

Developing alternate metabolic PWs

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

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

How do alterations of the target enzyme cause Ab resistance?

Through MODIFIED penicillin binding proteins

How do penicillin binding proteins usually work?

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

What are these PBP proteins for?

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

What do MPBPs do?

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

About MRSA and its alteration of PBP (target En)

Is S. aureus | Methicillin resistant caused by the expression of the mecA gene-->encodes PBP2a

What does PBP2a do?

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