3 - Antimicrobial Resistance 1 Flashcards
(53 cards)
What is an antimicrobial
Any substance that kills or slows the growth of bacteria but causes little or no damage to the host
Used in treatment of bacterial diseases
Antimicrobial vs antibiotic
Microbial = semi-synthetic, synthetic or natural compound
Antibiotic = naturally produced
Four classes of antimicrobials
- Antibacterial
- Antiviral
- Antifungal
- Antiparasitic
Antimicrobial uses in agriculture
- therapy
- prophylaxis / metaphylaxis
- growth promotion
What is prophylaxis vs metaphylaxis
Pro = preventative use
Meta = mass medication of an entire animal population to reduce the incidence of disease in a population that already has some evidence of disease
How is antimicrobial use in agriculture unique?
Administration at the group level
Whole populations of animals and their bacteria exposed to antimicrobials
Three mechanisms of action of antimicrobials
- Inhibit cell wall synthesis and cell membrane synthesis/maintenance
- Inhibit DNA replication (novobiocin) or DNA synthesis (sulphonamides)
- Inhibit protein synthesis
Slides 13-15
What is antimicrobial resistance
Bacteria resist the effects of an antimicrobial
Can be intrinsic or acquired
Intrinsic vs acquired AMR
Intrinsic: always resistant (some genetic mechanism)
Acquired: become resistant with exposure by acquiring resistance genes
Example of intrinsic resistance
Gram negative e coli will not respond to penicillin bc cell walls do not have receptors
“Intrinsic AMR” has recently been changed to what? Why?
Expected resistant phenotype
where >90% considered resistant
Determination of susceptibility phenotypic breakpoints are always exposure dependent (i.e. survival changes with dosing, modes of administration)
Brief history of resistance biology
1926 = Alexander Fleming discovers penicillin
Soon noticed some bacteria were resistant
Since then, resistance has emerged to every antimicrobial, starting with random gene mutations
Four mechanisms of resistance
- Reduced permeability
- Antimicrobial agent modification
- Active efflux
- Target modification
Explain the mechanism of reduced permeability
Intrinsically resistant bacteria would have permanent cell wall differences that do not let the drug in
If not, can change their cell wall or receptors so drug can no longer enter cell
Explain the mechanism of antimicrobial agent modification
Enzyme or protein in cell (wall, cytoplasm) that changes the form of the antimicrobial compound so it can no longer bind its receptor
Explain the mechanism of active efflux
Bacterial cell membrane/wall has efflux pump, spits antimicrobial back out before it binds its receptors
Can be upregulated upon exposure to a drug, not always compound specific
Explain the mechanism of target modification
Mutation or genetic change in receptor so antimicrobial can no longer bind it therefore cannot invoke its action
What is antimicrobial cross-resistance
A physiological adaptation that increases the resistance to a number of unique agents through a single resistance mechanism (often efflux pumps that can pump out multiple antimicrobials in a drug class, different drug classes, biocides, heavy metals, etc)
What is triclosan
Antimicrobial that was present in many toothpastes, handsoaps
Cross resistance is, simply, …
a single mechanism conveying resistance to multiple different types of compounds
What is AMR co-selection
Multiple resistance mechanisms/genes to otherwise unrelated drugs/compounds of different classes are selected together as a result of genetic linkage
Examples of what is and is not co-selection
e.g. resistance to penicillin and ampicillin (both beta-lactam class)… NO! single mechanism = cross-resistance
e.g. two mechanisms (one plasmid) = ampicillin + oxytetracycline resistance genes
Slide 38*
Co-selection
Mechanisms of getting resistance genes
- acquired gene mutations
- horizontal gene transfer (mobile genetic elements)
- recombination between genetic elements
