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Lecture 12

BIOC17H3 Lecture Notes - Lecture 12: Protozoa, Beta-Lactamase, Integrase


Department
Biological Sciences
Course Code
BIOC17H3
Professor
M Terebiznic
Lecture
12

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Lecture 12:
- antimicrobial: substance that kills or inhibits the growth of bacteria, fungi, protozoa, or viruses
either kill microbes (microbicidal) or prevent their growth (microbistatic)
- antibiotic: term used to define therapeutic drugs to treat bacterial infections
- majority of antimicrobials are natural products that certain bacteria and fungi produce and send
outside of their cells only very few synthetic antibiotics
- antimicrobial resistance: ability of microbes to grow in presence of a drug that would normally kill or
limit their growth
How does drug susceptible bacteria become drug resistant?
- use of antibiotics in clinical settings can have two effects: 1) kill S pathogens 2) select mutant resistant
strains to drugs used (side effect)
- emergence of antibiotic resistance is a consequence of improper use of antibiotics, which selects for
antibiotic resistant strains of bacteria
- if don’t take the antibiotic at proper time, will not have a high enough concentration to kill the
bacteria, and this will select for R bacteria
- multidrug resistance (MDR): ability of a living cell to show resistance to a wide variety of structurally
and functionally unrelated compounds
- selective pressure is the use of an antibiotic
- dissemination: entire population of bacteria become resistant from a single bacterial mutation
- can occur due to point mutations, that can lead to missense mutations (wrong amino acid and thus
different protein), nonsense mutations (encode stop codon), and silent mutations (encodes same amino
acid sequence, thus no mutation seen phenotypically)
- presence of beta lactamase is due to point mutation which lead to a change the bacterial substrate
profile
- then the genes can be passed to other bacteria via transduction, transformation and conjugation
- bacteria that has this type of beta lactamase, has a low MIC, and thus cannot survive in the presence of
the antibiotic (cifotaxin)
- however, if there are mutations, these increase the MIC level, and they will become resistant to ctx
Integrons and transposable elemnents
- insertion sequences encode enzyme Tpasas
- composite: two IS are close enough that they can jump together
- some genes contain the tem 1 antibiotic resistance gene, such that when they jump to a new area,
they bring the resistance with them
- integrons contain two conserved regions and a variable region between them
5 prime conserved contains integrase that allows recombination of genes when they get inserted into
another variable region
Circle areas between cassettes are areas where integrase will recognize the area and recombine,
integrating a cassette into a variable region
- intergrase can also disintegrate and take out cassette from area
- cassettes are generally always associated with antibiotic resistance genes
Dissemination: spread of resistant genes among the entire metagenome
Non essential plasmid contains genes that are not required for survival
Attc and atti regions (cassette and 5 prime) are very similar and integrase recognizes them and produces
a homolous recombination, inserting the cassette
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