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21 Cards in this Set

  • Front
  • Back

4 Main mechanisms of Antibiotic Resistance

1) Alter or destroy antibiotic (using enzymes)


- B-lactamase


2)Modify Antibiotic Target (DNA mutation or protein change)


- methylate bacterial ribosome (Erythromycin)


- amino acid substitutions in bacterial DNA gyrase (quinolone)


- alter bacterial Penicillin Binding Protein (beta lactams)


- phosphorylate, adenylate, or acetylate the target (aminoglycoside)




3) Exclude antibiotic from cell (pump it back out or don't let it in)


- efflex pumps in bacterial membrane (tetracycline)


- decrease permeability of porins in bacterial membrane (aminoglycoside)




4) Alter metabolic pathway (take other route)


- reduce or eliminate need for precursors for folic acid pathway (sulfonamide)

What are the 5 main bacterial cell targets for antibiotics?

1) DNA Gyrase


2) Ribosome


3) Cell Wall


4) Protein synthesis


5) Cell membrane

What are the major antibiotic classes (14)

1)B-lactam


2) Cephalosporin


3) Carbapenem


4) Glycopeptide


5) Cyclic Polypeptide


6) Polyketide


7) Phenicol


8) Aminoglycoside


9) Macrolide/Lincosamides Streptogramin


10) Quinolone


11) Rifamycin


12) Sulfonamide


13) Nitroimidazole


14) Polypeptide

What is the target of B-lactams?

Target: Cell Wall


Spectrum: Narrow to Broad

What is the target of Cephalosporin?

Target: Cell wall


Spectrum: narrow to broad

What is the target of carbapenem?

Target: cell wall


Spectrum: broad

What is the target of glycopeptide?

Target: cell wall


spectrum G+

What is the target of cyclic polypeptide?

Cell wall




Spectrum: G+

What is the target of polyketide?

Protein synthesis




Spectrum: broad

What is the target of phenicols?

Protein synthesis




Spectrum: Broad

What is the target of aminoglycosides?

Protein synthesis




Spectrum: broad

What is the target of macrolide/lincosamides Streptogramin?

Protein synthesis




Spectrum: G+



What is the target of quinolones?

DNA synthesis




Spectrum: G+

What is the target of rifamycins?

mRNA synthesis




Spectrum: G+, mycobacteria

What is the target of sulfonamides?

Folate synthesis




Spectrum: broad

What is the target of nitroimidazoles?

DNA



Spectrum: Anaerobes


What is the target of polypeptides?

Cell membrane




Spectrum: G-

How do B-lactam antibiotics work?

Penicillins and cephalosporins are the most widely used antibiotics (good specificity, low toxicity, good spectrum)




- Target cell wall biosynthesis, inhibiting bacterial growth by destabilizing the wall


- Bacterial target is the penicillin-binding proteins (PBP)


- PBP's help polymerize (cross-link) beta-glycan chains during cell wall formation




B-Lactam antibiotics look structurally similar to D-alanyl-D-alanine, fools PBP enzyme into using the antibiotic instead (= competitive inhibition)


- Irreversible binding to active site of PBP (non-competitive inhibition)


- prevents final cross-linking of peptidoglycan layer in cell wall synthesis


- disruption of cell wall synthesis = weak cell walls

4 B-lactam resistance mechanisms:

1) B-lactamase enzymes (most important)


2) Modification of penicillin-binding proteins (also important)


3) efflux pumps (new ones found every day)


4) Decreased permeability (porins in G- bacteria membrane)

3 main mechanisms by which bacteria can obtain non-chromosomal DNA:

Horizontal Genetic Exchange




Conjugation = Sex Pilus


- Plasmid transfer


- Transposon transfer


- Integron transfer




Transduction = Bacteriophage


- incorporation of phage DNA (carrying bacterial DNA) into chromosome or plasmid




Transformation


- Uptake of DNA fragments from environment

What are the 3 transferable genetic elements carrying antibiotic resistance genes?

1) Plasmids




2) Transposable elements


- Transposon


- integrons


- insertion elements




3) Phages