Mechanisms of resistance to antimicrobials

Question 1

6 main mechanisms of antibiotic resistance:

Answer 1

1. ) Antibiotic inactivation
2. ) Decreased antibiotic accumulation through impaired uptake or efflux
3. ) Target site insensitivity to agent
4. ) Bypass of antibiotic-sensitive step by duplication of target site (the duplicate is insusceptible)
5. ) Overproduction of target site so that higher conc of antiobiotic needed to inhibit bacterial growth.
6. ) Absence of an enzyme/metabolic pathway

Question 2

Resistance to B-lactams: Inactivation

Answer 2

1.) Bacterial enzymes inactivate the beta-lactams before they reach their PBP target. The enzymes are likely descended from PBPs. They are either found extracelluarly when excreted or in the periplasmic space. This constitutes the most important resistance mechanism to B-lactams in G-ve bacteria

Question 3

How do beta-lactamases act?

Answer 3

Either by using an ester hydrolysis mechanism or using a zinc ion to attack the B-lactam ring (MBLs).
Both methods depend on the activity of a nucleophillc group that donates electrons at the active site of the enzyme (on serine residue or Zn2+)