Antimicrobial Resistance

Question 1

Mechanisms of Resistance

Answer 1

• Exclusion
• Altered target
• Enzymatic inactivation

Question 2

Exclusion

Answer 2

Question 3

Altered Target

Answer 3

• β-Lactams
• Peptidoglycan transpeptidases (PBPs)

Question 4

Enzymatic Inactivation

Answer 4

β-Lactamase is a general term referring to any one of many bacterial enzymes able to break open the β-lactam ring and inactivate various members of the β-lactam group.

• Each β-lactamase is a distinct enzyme with its own physical characteristics and substrate profile.
• For example, the original staphylococcal penicillinase is also active against ampicillin but not against methicillin or any cephalosporin.
• Compounds like clavulanic acid are called b-lactamase inhibitors because they directly bind these enzymes. When used in combination they can provide a kind of “shield” for a b-lactam to act on bacteria.

Modifying Enzymes The most common cause of acquired bacterial resistance to aminoglycosides is through production of one or more of over 50 enzymes that acetylate, adenylate, or phosphorylate the aminoglycoside molecule.

• The chemically modified aminoglycoside no longer binds to the ribosome.
• Aminoglycoside-modifying enzymes represent a large and diverse group of bacterial proteins, each with its characteristic properties and substrate profile. Inactivating enzymes have been described for a number of other antimicrobials.

Question 5

Inntrinsic (chromosomal)

Answer 5

• Structure

– Outer membrane

• Metabolism

– Entry – anaerobes

– Inactivation - enzymes

Question 6

Acquired

Answer 6

• Mutation

• Entry porin
• Protein target
• Ribosomal binding site
• Regulatory protein

• Acquisition of new genes

• Transformation
• Transduction
• Conjugation
• (Transposition)