Antibiotic resistance in bacteria

Question 1

Penicillin

Answer 1

Beta-lactams inhibit cell wall synthesis
Bacterial cell wall is composed of peptidoglycan NAG-NAM chains crosslinked by peptide bridges
Penicillin inhibits linking enzymes (penicillin binding proteins) and blocks crosslinks
Cell bursts from osmotic pressure

Question 2

Penicillin resistance

Answer 2

Beta-lactamase degrades beta-lactam ring in penicillin to produce penicilloic acid

Alternative penicillin binding proteins that penicillin cannot bind.

Question 3

Protein synthesis antibiotics

Answer 3

All affect synthesis at ribosome
Streptomycin causes integration of incorrect amino acids into chain
Tetracycline blocks docking site of tRNA
Clarithromycin binds 50s subunit and blocks proper mRNA movement through ribosome

Question 4

Metabolic pathway antibiotics

Answer 4

PABA involved in folic acid synthesis in bacteria

Sulfonamides (antibiotic) are structural analogues of PABA and inhibit folic acid synthesis

Question 5

Causes of antibiotic resistance

Answer 5

Incorrect prescribing practices
Non-adherence by patients
Counterfeit drugs
Loss of effectiveness

Question 6

Types of resistance

Answer 6

Antibiotic has no target or cannot enter cell (passive)
Target site changes so antibiotic ineffective (mutation)
Actively acquired resistance (horizontal gene transfer)

Question 7

Streptomycin resistance

Answer 7

Streptomycin binds 16s rRNA of 30s subunit to inhibit protein synthesis

Mutation of 16s rRNA gene changes active site, so streptomycin ineffective

Question 8

MRSA

Answer 8

Methicillin resistant staphylococcus aureus
Resistant to beta lactams (penicillins), erythromycin and tetracycline
Gene spread by horizontal transfer
Vancomycin used but resistant strains have emerged

Question 9

MRSA virulence

Answer 9

Staphylococcal cassette chromosome mec (SCCmec) is a mobile genetic element that contains mecA gene
mecA encodes PBP2A (Penicillin binding protein 2A)
PBP2A has low affinity for beta-lactam antibiotics
Allows transpeptidase activity in presence of beta-lactams

Question 10

NDM-1

Answer 10

Provides resistance to carbapenems (beta-lactam antibiotics developed to overcome beta-lactamase enzymes)
NDM-1 is carbapenemase beta-lactamase.
Commonly found in E. coli and Klebsiella pneumoniae (gram negative)
Spread by horizontal transfer

Question 11

NDM-5

Answer 11

Variant of New Delhi metallo-enzyme (NDM)

Resistant to all cephalosporins, carbapenems, aminoglycosides, quinolones.

Question 12

Managing resistance

Answer 12

Manage existing pathogens by improving hospital hygiene
Reduce inappropriate antibiotic prescription
Reduce agricultural antibiotic use
Restrict use of new antibiotics
Other treatments (vaccines, phage therapy)