lecture 7) persistant and chronic infections Flashcards
“if antibiotics and immune systems were 100% effective there would be no infections”. why isnt this the case in clinical practice?
persistant and chronic infections exist
why dont antibiotics kill all infections?
bacterial populations include persister cells, phenotypic variants
what is the main cause of antibiotics being unable to clear infections?
multidrug tolerance of persister cells
is there a genetic difference between bacterial cells and persister cells?
no
are persister cells mutants?
no because they dont grow in the presence of antibiotics
what makes normal bacterial cells different to persister cells if they are genetically the same?
persister cells arent growing
if persister cells are genetically identical to normal bacterial cells, what does this mean in terms of their phenotype?
they are phenotypic variants of the wild type
where in terms of growth phases are persister cells present?
mostly at the stationary phase
most persister cells are found at the stationary phase of growth. what does this suggest?
that optimal individual strategy is not to enter persistence
persister state is an alturistic behaviour benefiting the kin. what is meant by the term kin?
organism favours genetically related individuals over non-related organisms in social behaviours
if the whole bacterial population was killed by a lethal factor, what cells would remain and what would they do?
persister cells would remain
they would propagate genome with their kin
are these cells thinking??
are all cells equal?
no
when looking at individual cells you may have low/medium/high producers
when would evaluating if all cells are equal become problematic?
when looking at big cultures
if all cells in a bacterial population are genetically identical, how are persister cells produced?
by a stochastic process (random)
name the 2 process involved in mechanism of persistence
stochastic fluctuation
controlled and regulated mean of expression
what does stochastic fluctuation refer to in mechanism of persistence?
happens in level of specific persister proteins
what does controlled and regulated mean of expression refer to in mechanism of persistence?
happens in specific persister proteins depending on density of population
what influence does the environment have on stochastic fluctuation?
the environment sets a baseline for stochastic fluctuation
why would a cell be in growth arrest?
something is inhibiting essential cellular processes eg DNA replication, protein synthesis
what could be causing inhibition of essential processes of cells leading to persister cell formation?
toxins
environmental cues leading to toxin release
what are toxin antitoxin systems?
colocated on plasmids (ineffective complex) or chromsome on gene locus (locus = toxin and antitoxin gene)
constant fluctuation
cellular proteases controlling the environment
environmental factors
what would cause the degradation of the toxin-antitoxin system?
elevated proteases
what happens if a toxin antitoxin where to become degraded due to elevated proteases?
toxin would be liberated which would initiate growth arrest
suggest why the protease wouldnt degrade the toxin
secondary structure of the toxin could be preventing the protease from degrading it
when is quorum sensing more active?
in higher density populations
what impact does quorum sensing have on persister cells?
quorum sensing produces a higher proportion of persister cells in a bacterial culture
suggest a reason why antibiotics may not work against persister cells
they are tolerant to the antibiotics (cope with anitbiotics but antibiotics wont kill them)
have a mechanism for tolerance eg efflux pump
is antibiotic tolerance genetic?
no
are persisters in biolfims able to regrow after cessation of antibiotic therapy?
yes
why is there no commercial driver to treat persister cells?
FDA only approve antibiotics for actively growing cells
what is the impact of antibiotic treatment on persister cells?
serially reducing the concentration of antibiotic gives fewer persister cells with each round of treatment
