Antibiotic Resistance Flashcards
how does antibiotic resistance happen (4)
- 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
what ultimately causes antibiotic resistance (2)
- simply using antibiotics
why has antibiotic resistance (5)
- 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
mechanisms of resistance (4)
- intrinsic resistance
- enzymatic inactivation of the antibiotic
- efflux pumps
- target modification
mechanisms of intrinsic resistance (2)
- barrier function
- detoxification
intrinsic resistance: barrier function (2)
- outer membrane or cell wall
- antibiotic is excluded from the cell
intrinsic resistance: detoxification (2)
- scavenging-thiol mediated
- compounds bind the antibiotic (the toxin) and neutralize it
what are the three general strategies to achieve drug resistance (3)
- drug resistance due to altered targets
- drug resistance due to decreased accumulation (low permeability or high efflux)
- drug resistance due to enzymatic inactivation
efflux pumps: specificity (2)
- hallmark of multi-drug resistance
- some are very specific, whereas others can pump variety of antibiotics
efflux pumps: common features (3)
- inner membrane pump
- outer membrane pump
- membrane fusion protein in periplasm that links IM to OM
enzymatic inactivation of the antibiotic: beta-lactam antibiotics
- beta-lactamases inactivate penicillin and derivatives (beta-lactams)
enzymatic inactivation of the antibiotic: mechanism (2)
- adds modifying groups to inactivate the antibiotic
- mechanism of resistance to aminoglycosides
enzymatic inactivation of antibiotic: modifying groups (3)
- methyl
- acetyl
- phosphate
how can beta-lactamases be overcome
- augmentin
augmentin example and antibiotic it helps (2)
- clavulanic acid
- amoxicillin
how does clavulanic acid work (2)
- covalently binds to serine residues in active site of the beta-lactamase
- inactivates beta-lactamase and allows amoxicillin to work
bacteria outcome: beta-lactam
- kills bacteria
bacteria outcome: beta-lactam + beta-lactamase (2)
- beta-lactam inactivated
- no effect on bacteria
bacteria outcome: beta-lactam + beta-lactamase + clavulanic acid (3)
- inactivated beta-lactamase
- beta-lactam unaffected
- kills bacteria
target modifications (2)
- change the transpeptidase
- change to PG precursors
target modification of transpeptidase: which bacteria show this resistance
- methicillin resistance S. aureus (MRSA)
MRSA: transpeptidase (3)
- name
- gene
- similarity to other transpeptidases
- Pbp2a
- encoded by the mecA gene
- 20% sequence identity to other Pbps
how does the MRSA Pbp2a facilitate resistance (2)
- has an altered or slightly distorted active site
- prevents binding of methicillin while still allowing transpeptidases to occur
how does resistance arise in MRSA (3)
- mobile genetic element that houses the mecA gene
- came from Staphylococcus strains (not S. aures)
- rapidly spread between S. aures strains
target modification of PG precursors: what antibiotic is affected
- vancomycin
what type of antibiotic is vancomycin
- glycopeptide antibiotic
vancomycin: mechanism of action (3)
- binds the D-ala D-ala part of the PG precursor
- prevents transglycosylation and transpeptidation
- PG biosynthesis is inhibited and eventually bacteria dies
what is the vancomycin mechanism of resistance (3)
- vancomycin-PG precursors accumulate in cell membrane
- VanS senses this and phosphorylates itself and VanR
- VanR activates expression of vanX, vanH, and vanA genes
VanR (2)
- transcription factor
- activated after it is phosphorylated
vanX (2)
- peptidase
- eliminates D-ala D-ala PG precursor
VanH and VanA
- enable synthesis of D-ala D-lactate, which vancomycin does not bind
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
how does vancomycin resistance arise (3)
- all resistance genes carried on a transposon
- transposon resides on a conjugative plasmid
- resistance can spread quickly
conjugative plasmid (2)
- a mobile genetic element
- encodes transfer apparatus
multi-drug resistance (MDR) mechanism (2)
- efflux
- integrons
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
integrons (2)
- what is it
- role
- mobile genetic elements
- capture and mobilize “gene cassettes” via site-specific recombination
integrons: gene cassettes (2)
- all have 59bp element
- do not have their own promoters
how do integrons and gene cassettes interact
- 59bp element of gene cassette interacts with att site on the integron
how are gene cassettes connected to a promoter (2)
- rely on promoter in the integron
- located within the integrase gene, int
what are the origins of antibiotic resistance (2)
- antibiotic-producing microbes
- altered houeskeeping genes that recognize new substrates
