Antibiotics: mechanism of resistance

Question 1

Penicillins?

Answer 1

Mechanism of Resistance:

• Bacterial penicillinase (β-lactamase) cleaves β-lactam ring

Question 2

Cephalosporins?

Answer 2

Mechanism of Resistance:

• Changes to penicillin-binding-proteins (PBPs), which are types of transpeptidases*

Question 3

Macrolides?

Answer 3

Mechanism of Resistance:

• Post-transcriptional methylation of the 23S bacterial ribosomal RNA

Question 4

• Fluoroquinolones?

Answer 4

Mechanism of Resistance:

• Mutations to DNA gyrase, efflux pumps which reduce intracellular quinolone concentration

Question 5

Tetracyclines?

Answer 5

Mechanism of Resistance:

• Increased efflux of the bacteria by plasmid-encoded transport pumps, ribosomal protection

Question 6

Aminoglycosides?

Answer 6

Mechanism of Resistance:

• Plasmid-encoded genes for acetyltransferases, adenyltransferases and phosphotransferases

Question 7

Sulfonamides?

Answer 7

Mechanism of Resistance:

• Bacteria increase synthesis of PABA, mutation to gene encoding dihydropteroate synthetase

Question 8

Vancomycin?

Answer 8

Mechanism of Resistance:

• Alteration to the terminal amino acid residues of the NAM/NAG-peptide subunits (normally D-alanyl-D-alanine) to which the antibiotic binds

Question 9

Rifampicin?

Answer 9

Mechanism of action:

• Mutations altering residues of the rifampicin binding site on RNA polymerase

Question 10

Isoniazid?

Answer 10

Mechanism of action:

• Mutations in katG gene resulting reducing the ability of the catalase-peroxidase to activate the pro-drug

Question 11

Pyrazinamide?

Answer 11

Mechanism of action:

• Mutations in the pncA gene encoding PZase, reducing conversion of the pro-drug

Question 12

Answer 12