Antibiotic Resistance Flashcards
(41 cards)
1
Q
how does antibiotic resistance happen (4)
A
- lots of germs present, with few being drug resistant
- antibiotics kill bacteria causing illness and good bacteria protecting body from infection
- drug-resistant bacteria grow and take over without competition
- some bacteria give their drug resistance to other bacteria, causing more problems
2
Q
what ultimately causes antibiotic resistance (2)
A
- simply using antibiotics
3
Q
why has antibiotic resistance (5)
A
- mutation and selection
- exchange of resistance genes between bacteria
- exchange of bacteria between people
- inappropriate use of antibiotics by physicians/patients
- inappropriate use of antibiotics to enhance the growth of livestock
4
Q
mechanisms of resistance (4)
A
- intrinsic resistance
- enzymatic inactivation of the antibiotic
- efflux pumps
- target modification
5
Q
mechanisms of intrinsic resistance (2)
A
- barrier function
- detoxification
6
Q
intrinsic resistance: barrier function (2)
A
- outer membrane or cell wall
- antibiotic is excluded from the cell
7
Q
intrinsic resistance: detoxification (2)
A
- scavenging-thiol mediated
- compounds bind the antibiotic (the toxin) and neutralize it
8
Q
what are the three general strategies to achieve drug resistance (3)
A
- drug resistance due to altered targets
- drug resistance due to decreased accumulation (low permeability or high efflux)
- drug resistance due to enzymatic inactivation
9
Q
efflux pumps: specificity (2)
A
- hallmark of multi-drug resistance
- some are very specific, whereas others can pump variety of antibiotics
10
Q
efflux pumps: common features (3)
A
- inner membrane pump
- outer membrane pump
- membrane fusion protein in periplasm that links IM to OM
11
Q
enzymatic inactivation of the antibiotic: beta-lactam antibiotics
A
- beta-lactamases inactivate penicillin and derivatives (beta-lactams)
12
Q
enzymatic inactivation of the antibiotic: mechanism (2)
A
- adds modifying groups to inactivate the antibiotic
- mechanism of resistance to aminoglycosides
13
Q
enzymatic inactivation of antibiotic: modifying groups (3)
A
- methyl
- acetyl
- phosphate
14
Q
how can beta-lactamases be overcome
A
- augmentin
15
Q
augmentin example and antibiotic it helps (2)
A
- clavulanic acid
- amoxicillin
16
Q
how does clavulanic acid work (2)
A
- covalently binds to serine residues in active site of the beta-lactamase
- inactivates beta-lactamase and allows amoxicillin to work
17
Q
bacteria outcome: beta-lactam
A
- kills bacteria
18
Q
bacteria outcome: beta-lactam + beta-lactamase (2)
A
- beta-lactam inactivated
- no effect on bacteria
19
Q
bacteria outcome: beta-lactam + beta-lactamase + clavulanic acid (3)
A
- inactivated beta-lactamase
- beta-lactam unaffected
- kills bacteria
20
Q
target modifications (2)
A
- change the transpeptidase
- change to PG precursors
21
Q
target modification of transpeptidase: which bacteria show this resistance
A
- methicillin resistance S. aureus (MRSA)
22
Q
MRSA: transpeptidase (3)
- name
- gene
- similarity to other transpeptidases
A
- Pbp2a
- encoded by the mecA gene
- 20% sequence identity to other Pbps
23
Q
how does the MRSA Pbp2a facilitate resistance (2)
A
- has an altered or slightly distorted active site
- prevents binding of methicillin while still allowing transpeptidases to occur
24
Q
how does resistance arise in MRSA (3)
A
- mobile genetic element that houses the mecA gene
- came from Staphylococcus strains (not S. aures)
- rapidly spread between S. aures strains
25
target modification of PG precursors: what antibiotic is affected
- vancomycin
26
what type of antibiotic is vancomycin
- glycopeptide antibiotic
27
vancomycin: mechanism of action (3)
1. binds the D-ala D-ala part of the PG precursor
2. prevents transglycosylation and transpeptidation
3. PG biosynthesis is inhibited and eventually bacteria dies
28
what is the vancomycin mechanism of resistance (3)
1. vancomycin-PG precursors accumulate in cell membrane
2. VanS senses this and phosphorylates itself and VanR
3. VanR activates expression of vanX, vanH, and vanA genes
29
VanR (2)
- transcription factor
- activated after it is phosphorylated
30
vanX (2)
- peptidase
- eliminates D-ala D-ala PG precursor
31
VanH and VanA
- enable synthesis of **D-ala D-lactate**, which vancomycin does not bind
32
what is the result of the vancomycin mechanism of resistance (3)
- transglycosylation and transpeptidation can now occur
- D-lac now **hydrolyzed** during peptidation instead of D-ala
- results in "unaltered" PG synthesis
33
how does vancomycin resistance arise (3)
- all resistance genes carried on a transposon
- transposon resides on a conjugative plasmid
- resistance can spread quickly
34
conjugative plasmid (2)
- a mobile genetic element
- encodes transfer apparatus
35
multi-drug resistance (MDR) mechanism (2)
- efflux
- integrons
36
why are integrons related to MDR (3)
- found in many MDR strains
- sequencing results showed that often resistance genes are found in tandem
- strains resistant to a wide variety of anti-microbials
37
integrons (2)
- what is it
- role
- mobile genetic elements
- capture and mobilize "gene cassettes" via site-specific recombination
38
integrons: gene cassettes (2)
- all have 59bp element
- do not have their own promoters
39
how do integrons and gene cassettes interact
- **59bp element** of gene cassette interacts with **att site** on the integron
40
how are gene cassettes connected to a promoter (2)
- rely on promoter in the integron
- located within the integrase gene, int
41
what are the origins of antibiotic resistance (2)
- antibiotic-producing microbes
- altered houeskeeping genes that recognize new substrates
