Antibiotic Resistance

Question 1

What are three types of intrinsic drug resistance?

Answer 1

• Metabolic inactivity
• Lack of target structure
• Exclusion

Question 2

What are two types of genetic resistance?

Answer 2

• Chromosomal resistance

- Acquired genes

Question 3

How does chromosomal resistance arise?

Answer 3

Through spontaneous mutation
Relatively rare (10^-7 to -12)
Results in modification of target (e.g. change PBP type so drug has no effect)

Question 4

What are the mechanisms to acquired genes?

Answer 4

Transformation
Conjugation - most common
Transduction

Question 5

What are 6 antibiotic resistance mechanism?

Answer 5

1. Exclusion of antibiotic from site of action
2. Efflux pump for the antibiotic to remove from site of action
3. Enzymatic modification
4. Destruction
5. Modified antibiotic-insensitive target
6. New antibiotic-insensitive target

Question 6

What are some Beta-Lactam antibiotic classes?

Answer 6

Penicillins
Cephaosporins
Carbapenems (Streptomyces)

Question 7

Are Gram-negative bacteria resistant to penicillin?

Answer 7

Yes
Gram-negative have an intrinsic resistance (cant penetrate OM) => ampicillin and amoxycillin can penetrate some (extended spectrum antibiotics)

Question 8

What are Beta-Lactamases?

Answer 8

Serine proteases
>200 known
Most have specificity to Beta-Lactams
Extended spectrum BLs exist, and have zinc-dependent metalloenzymes
Methicillin, oxacillin and nafcillin are resistant to Beta-Lactamases

Question 9

How are bacteria resistant to methicillin and oxacillin?

Answer 9

New PBP, mainly in gram-positives. BLs don’t target as well. Genes can be found on SCCmec => MRSA.

Question 10

What is SCCmec?

Answer 10

A piece of chromosome that can become integrated.
SCCmecII -> mainly hospital. Also contains antibiotic resistance genes such as macrolide, lincosomide, streptogramin B
SCCmecIV -> mainly community.

Question 11

How does vancomycin work?

Answer 11

It inhibits PG synthesis by binding to the penta-peptides of the PG monomers. Crosslinking is prevented (lack of strength)
Useful for MRSA

Question 12

How is VISA resistant to vancomycin?

Answer 12

Through a reduced permeability of the cell wall

Question 13

How do VRE and VRSA arise?

Answer 13

They acquire a large gene cassette, potentially able to horizontally transfer from E to Staph

Casette contains vanR, vanS vanH (dehydrogenase), vanA (ligase), vanX (dipeptidase) vanY (carboxypeptidase) and vanZ

Question 14

What are some antibiotics that inhibit protein synthesis?

Answer 14

Aminoglycosides (streptomycin)
Tetracyclines
Lincosamides (clindamycin)
Macrolides (erythromycin)
Chloramphenicol

Question 15

How can bacteria become resistant to antibiotics that target protein synthesis?

Answer 15

• Efflux pumps
• Mutational modification of rRNA, or ribosomal proteins
• Enzymatic modification of rRNA, or antibiotic