8/9 drug resistance

Question 1

natural resistance = innate resistance = insensitivity

Answer 1

• occurs in most or almost all strains of bacteria
• lack of sensitive target
• inefficient abx penetration
• export by naturally occuring transporters
• insensitivity of aerobes to metronidazole (cant reduce it)

Question 2

inefficient abx penetration examples

Answer 2

vancomycin - cant do Gneg
aminoglycosides arent taken up by anaerobes
biofilm decreases perm

Question 3

characteristics of natural resistance

Answer 3

• stable

- not easily spread

Question 4

where does acquired resistance arise?

Answer 4

1. mutation (point mut or gene duplication/amplification)
2. acquire new genes

**prevalent in clinical setting

Question 5

rifampin res point mutation

Answer 5

in beta subunit of RNA polymerase

Question 6

quinolone res point mutation

Answer 6

(nalidixic acid)

single base mutation in DNA gyrase alpa SU gene

Question 7

penicillin res point mutations

Answer 7

in PBP gene

Question 8

linezolid res pt mutation

Answer 8

**this is the MRSA drug i think

point mutations in 23s rRNA gene

Question 9

gene duplication and amplification examples

Answer 9

overproduce. …
- abx modifying enzymes (b-lactamases)
- target molecules
- efflux pump

Question 10

5 modes of resistance

Answer 10

1. abx destroyed/modified by bacteria
2. prevent uptake/penetration of drug
3. efflux = active export
4. modify drug target
5. bypass mechanism

Question 11

1. example of abx destruction - b-lactams

Answer 11

• beta lacatamase
• penicillinase hydrolyzes beta lactam ring
• G neg adn pos

***use augmentin to block or use more resistant b-lactams

Question 12

1. abx destruction/enzymatic alteration - aminoglycosides

Answer 12

(genta, kana, streptomycin…irreversibly binds 30S SU)

• enzymatic alteration to detoxify drug using adenylase, phosphotransferase, acetyl transferase
• drug has decreased affinity for ribosome
• G neg and pos

Question 13

1. enzymatic alteration of chloramphenicol

Answer 13

(last resort drug, binds 50S)

• chloramphenicol transacetylase is bacterial enzyme that acetylates OH groups
• interferes with uptake
• Gneg adn pos

Question 14

4. modify drug target, : macrolide/lincosamide

Answer 14

-methylate 23S rRNA of sensitive cells which makes it so that drug cannot bind target, whihc is 50S SU

Question 15

4. modify drug target - b-lactam

Answer 15

• pbp mutations in s.pneumoniae, genes obtained by transformation
• source is often S.mitis

Question 16

why does the chart of s. pneumoniae isolates with abx res show decrease for penicillin in 2008

Answer 16

they changed the standard of resistance

Question 17

4. modify drug target - vancomycin (G pos)

Answer 17

glycopeptide that attaches to D-ala-D-ala terminal AA of peptide crosslink between NAM

change it to D-ala-D-ser or D-ala-D-lac

vanA mediated vancomycin resistance

Question 18

vanA mediated vancomycin resistance

Answer 18

• enzyme that removes terminal D-ala to increase frequency of D-ala-D-lac
• D-ala-D-lac instead of D-ala-D-ala

Question 19

5. bypass mechanism for b’lactam drugs

Answer 19

PBP2A can do job of all PBPs and is not susceptible to b-lactam cleavage

mecA is the gene

**MRSA !!!

Question 20

what do PBPs do?

Answer 20

cross link peptidoglycan

Question 21

mecA

Answer 21

encodes PBP2a (b-lactam resistance, MRSA)

Question 22

5. bypass - sulfonamides and trimethoprim

Answer 22

• drug resistant dihydropteroate synthetatse (sulf) or DHF reductase
• taken up on R plasmid or acquired via mutation

Question 23

ESKAPE pathogens

Answer 23

enterococcus
staphy aureus
Klebsiella pneumonia
Acinetobacter
psuedomonas aeurginosa
enterbobacter

Question 24

carbapenem resistant enterobacteriaceae

Answer 24

big problem