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MICR2209 > 20 - Antibiotic Resistance and Genetics > Flashcards

20 - Antibiotic Resistance and Genetics Flashcards

1
Q

4 main bacterial antibiotic resistance mechanisms

A
  1. Altered antibiotic target
  2. Inactivate antibiotic (Degrading the antibiotic or Chemically modify antibiotic)
  3. Reduced antibiotic accumulation
  4. alternate pathway to bypass the inhibited one
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2
Q

Altering the target of the antibiotic

A
  • Target protection
  • Target modification
  • Insensitive functional target
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3
Q

Target protection

A

Resistance protein blocks access of antibiotic target

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4
Q

Target modification

A

Resistance enzyme modifies antibiotic target

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5
Q

Vancomycin resistance

A

arises when bacteria change the terminal D-ala in the pentapeptide of peptidoglycan into D-serine or D-Lac, so vancomycin cannot bind

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6
Q

Insensitive functional target

A

Resistance protein is an alternative enzyme that is insensitive to antibiotic

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7
Q

Antibiotic degradation

A

Hydrolysis of the β-lactam ring of penicillins and cephalosporins by penicillinase (β-lactamase) enzymes

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8
Q

Chemically altering antibiotic

A

Acetyltransferase adds an acetyl group to aminoglycosides or
chloramphenicol, inactivating them

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9
Q

Reduced antibiotic accumulation

A

Antibiotic efflux

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10
Q

Antibiotic efflux

A
  • Rapid extrusion of antibiotic via efflux pump
  • Extrusion is energy dependent
  • Bacteria can also reduce uptake
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11
Q

Target bypass

A

Enterococci are intrinsically resistant to sulphonamides because they are able to use pre-formed folic acid from their environment (unlike other bacteria)

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12
Q

Vertical gene transfer

A

Transfer of genes from parent to progeny

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13
Q

Horizontal gene transfer

A
  • Transfer of genes from one independent, mature organism to another
  • Important in bacterial evolution, including the gain of antibiotic-resistance genes
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14
Q

Four possible fates of HGT donor DNA in the recipient cell

A
  • Integration via recombination with recipient’s genome
  • Self-replication of the donor DNA (if plasmid)
  • No replication and eventual loss of donor DNA
  • Degradation of donor DNA
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15
Q

Mobile genetic elements

A

DNA segments that can move to different locations on genomes and/or move from cell to cell.

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16
Q

Examples of mobile genetic elements

A
  • Plasmid
  • Transposable element
  • Integron
17
Q

Plasmid

A

Double-stranded DNA molecule, usually circular, that can exist and replicate independently of the chromosome

18
Q

Resistance (R) plasmid

A
  • A plasmid bearing one or more antibiotic-resistance genes
  • Gene cassette encoding antibiotic resistance inserts into integron which inserts into transposon which in turn inserts into a plasmid
19
Q

Transposable element

A

Small linear DNA molecule that carries genes for transposition and thus can move around the genome, or from one genome to
another (e.g. from plasmid to chromosome) via recombination

20
Q

Transposon

A
  • Also carries other genes such as antibiotic resistance genes
  • Is found as part of a bacterial chromosome or a plasmid, cannot self-replicate
21
Q

Integron

A
  • Very small linear DNA molecule which can capture even smaller “gene cassettes” encoding antibiotic resistance
  • Is found as part of a transposon or a plasmid, cannot self-replicate
22
Q

Three main mechanisms of horizontal gene transfer in bacteria

A
  • Conjugation
  • Transduction
  • Transformation
23
Q

Conjugation

A

Gene transfer mediated by plasmids that requires contact between cells

24
Q

Transduction

A

Gene transfer mediated by bacteriophages

25
Q

Transformation

A
  • The uptake of a piece of free DNA by a cell
  • Both chromosomal DNA and plasmid DNA can be transformed
26
Q

Process of conjugation

A
  1. F plasmid encodes proteins to build the sex pilus and the protein
    systems that perform DNA transfer
  2. Sex pilus tip binds to recipient cell. Pilus retracts, pulling donor and recipient cells together to make contact and form a mating pore
  3. Plasmid is nicked (one strand is cut), rolling circle replication of plasmid DNA starts
  4. Both cells recircularize their plasmids, synthesise second strands to form double-stranded plasmids, and form pili; both cells are now viable donors in conjugation
27
Q

Relaxosome

A

Protein complex including a relaxase protein that nicks and unwinds the DNA, ready for transfer of a single DNA strand through the pore

28
Q

Transferosome / T4SS

A

Pushes the DNA/relaxase complex into the recipient cell

29
Q

Virulent phage

A

Only have a lytic cycle

30
Q

Temperate phages

A

Have a lytic cycle, or a lysogenic cycle

31
Q

Lytic cycle

A
  • Phage injects its DNA into cytoplasm
  • Phage DNA directs the synthesis of many new phages
  • Cell lyses and releases the new phages
  • New phages can bind to bacterial cells
32
Q

Lysogenic cycle

A
  • Phage DNA integrates into bacterial host’s chromosome to form a lysogen.
  • Phage DNA is inactive (prophage) and replicated along with chromosome
  • Host cell does not lyse and grows normally.
33
Q

Prophage induction

A

Exposure to stress such as UV light triggers activation of the prophage and its excision from the host chromosome – lytic cycle
resumes

34
Q

Generalised tranduction

A
  • Transfer of any genes from donor
  • Occurs during the lytic cycle of virulent and temperate phages
  • Bacterial genes are packaged by mistake into a phage head (capsid). Phage carries only bacterial genes (i.e. no phage genes).
  • Any bacterial gene can be transduced, including antibiotic resistance genes
35
Q

Specialised tranduction

A
  • Transfer of only genes adjacent to prophage
  • Occurs during the lysogenic cycle of temperate phages only
  • Transducing phage carries mainly phage genes plus some bacterial genes, which it will inject into its next host cell to form a transductant
  • Only certain bacterial genes will be in the right location to be picked up and transduced by the temperate phage (i.e. they were right next to the
    prophage)
36
Q

Misuse of antibiotics

A
  • Use as growth enhancers in animals
  • Non-completion of antibiotic courses
  • Unregulated antibiotic sales
  • Use of wrong or suboptimal antibiotic doses

MICR2209 (26 decks)

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