Genetics of Bacterial Antibiotic Resistance Flashcards

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1
Q

describe a prokaryote

A
  • Cell wall
  • DNA is within the cytoplasm of the cell
  • Has a flagella
  • Smaller 2um
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2
Q

Describe a Eukaryote

A
  • Nucleus
  • Cytoplasm
  • Organelles
  • 20um
  • Has a cell membrane
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3
Q

What must antibiotics be

A
  • Must be toxic to the bacteria but not the host
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4
Q

when did resistance to antibiotic develop

A
  • From the first use of antibiotics there were some bacteria that couldn’t be inhibited by some antibiotics
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5
Q

Name mechanisms of action of antibiotics

A
  • inhibit cell wall synthesis
  • inhibit protein synthesis
  • folate metabolism is also inhibited
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6
Q

How does antibiotic resistance develop

A
  1. Mutation of the drug target
  2. Breakdown of the antibiotic
  3. Modification of the antibiotic
  4. Efflux of the antibiotic
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7
Q

How does rifampicin works

A
  • Rifampicin inhibits RNA polymerase preventing RNA production and is bactericidal
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8
Q

Give examples of target site mutations for drugs

A
  • Rifampicin
  • streptomycin
  • ciprofloxacin
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9
Q

Describe how the bacteria can break down the antibiotics

A
  • Resistance bacteria degrade the B lactam – produces a beta lactamase enzyme that breaks down penicillin
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10
Q

Describe how bacteria can modify the antibiotic to prevent it from working

A
  • Bacteria acquire genes encoding aminoglycoside modifying enzymes
  • These add small molecules to the drug to prevent it binding
  • Produce enzymes that modifies the aminoglycoside so it can no longer bind to the ribosome
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11
Q

Describe how bacteria can effect the efflux of antibiotics

A
  • Bacteria may up-regulate existing pump
  • By mutation – may arise during treatment
  • Bacteria may acquire genes for new pump
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12
Q

what antibiotics are effected by efflux mutations

A
  • Tetracycline
  • Chloramphenicol
  • Fluoroquinolones
  • Beta lactams
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13
Q

How can resistance genes be acquired by bacteria

A
  • plasmid transfer
  • transposable elements
  • transformation
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14
Q

describe how resistance genes can be acquired by bacteria by plasmid transfer

A

 F (fertility) factors are classic example of conjugative plasmids
 F+ cells produce F pili involved in making contact with recipient
 plasmid transfer involves replication

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15
Q

How can resistance genes be acquired via transposable elements

A

 DNA sequences capable of excision and insertion into new locations in chromosome or plasmid
 Simplest elements are insertion sequences (IS) which encode transposase gene flanked by inverted repeats
 Many genomes contain several ISs, some in multiple copies
- Transposition results in the duplication of the target sequence

 transfer genes from plasmid to plasmid
 conjugative transposons transfer from one cell to another (cf conjugative plasmids)
 transfer genes between plasmid and chromosome
 pick up chromosomal genes

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16
Q

What is an integron

A

special class of composite element carrying gene cassettes

17
Q

Describe the structure of integrons

A

 Each integron contains up to 5 cassettes
 More than 60 different cassettes have been found
 Most are antibiotic resistance determinants

18
Q

How can resistance genes be acquired by transformation

A

 transfer of naked DNA
 DNA integrated into chromosome by
homologous recombination
 Replacement of an existing chromosomal gene with a resistant variant
 E.g. Streptococcus pneumoniae penicillin resistance

19
Q

Where do resistance genes originate

A

 Antibiotics are natural products
 e.g. penicillin from mould

 Bacteria in the environment have co- evolved
 e.g. CTX-M β-lactamase originated in Kluyvera spp found in soil

20
Q

What can we do about antibiotic resistance

A
  • Develop new antimicrobials
  • Antibiotic development is decreasing
  • If we did get a new development we wouldn’t want to use it therefore drug companies wouldn’t make the money back that it costs to develop it