antimicrobial resistance Flashcards
estimated deaths a year from amr
10million- GRAM, 2024
examples of antibiotic classes
beta lactams- target the cell wall
quinolones- target dna replication machinery
4 HGT mechanisms
conjugation- pillus
transduction- phage
vesiduction- vesicles
transformation- free
what is mic
minimum inhibitory concentration- min conc needed to kill off the bacteria, we want to get to this to avoid selecting for resistance
resistance evolution model
resistance needs to stabilise (through ‘compensatory mutation’), or it will be lost
example of successful combination therapy
HAART
case study of multiple antibiotics being used and helping prevent resiatance
nfxB mutations common in P. aeurigonosa treated with Quinolones. involves turning on an efflux pump
can use an Aminoglycoside, which select against these mutations (it actually pumps them out)
issues with a multidrug approach
bystander effects- exposing other bacteria to more antibiotics
hard to apply as it can be so niche
how rare is reversion under lab conditions
happens in about 1 in a billion genes per generation
example of a compensatory adaptation
rpoB- mutation on the binding site of RNAP
rpoC restores functionality without reverting the original mutation
how does resistance look in a real population
majorly rises, then crashes also very quickly- mutations are getting replaced or removed
role of body systems in encouraging mutation
refugia and immigration- bacteria tend to be in a certain area (refugia), other stuff moves in which is probably sensitive and takes over for other reasons- just dont stick around
resistant mutants are still susceptible to immunity like anything else
chromosomal vs plasmid importance
plasmid-encoded resistance is much more stable, and carries a smaller fitness cost (more like 5% vs 20%)
resistance genes in commensals
actually mostly just don’t spread to pathogens- but they can do so
example of a response to the emergence of a resistance gene
PV3 mutant of E. coli in pigs- spread to humans- stopped using colistin (the agricultural antibiotic that was used), and the strain went down loads
source and sink theory
plasmid costs vary between species and strains, so you see ‘source’ species where there are a load of plasmids and ‘sink’ species which just take them up- helps maintain plasmids in the population
why is compensatory evolution especially an issue in plasmids
the low-cost plasmids can spread like hell because they’re low-cost
why the plasmid idea might not entirely explain the dynamics of resistance we see
don’t actually see free transfer like you might expect- stuff that just Will Not move into pathogens
narrow host ranges a lot of the time
xenogenic immunity (i.e. bacterial defense systems say NO to plasmids e.g. restriction-modification system)
