lecture 7) persistant and chronic infections Flashcards

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1
Q

“if antibiotics and immune systems were 100% effective there would be no infections”. why isnt this the case in clinical practice?

A

persistant and chronic infections exist

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2
Q

why dont antibiotics kill all infections?

A

bacterial populations include persister cells, phenotypic variants

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3
Q

what is the main cause of antibiotics being unable to clear infections?

A

multidrug tolerance of persister cells

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4
Q

is there a genetic difference between bacterial cells and persister cells?

A

no

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5
Q

are persister cells mutants?

A

no because they dont grow in the presence of antibiotics

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6
Q

what makes normal bacterial cells different to persister cells if they are genetically the same?

A

persister cells arent growing

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7
Q

if persister cells are genetically identical to normal bacterial cells, what does this mean in terms of their phenotype?

A

they are phenotypic variants of the wild type

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8
Q

where in terms of growth phases are persister cells present?

A

mostly at the stationary phase

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9
Q

most persister cells are found at the stationary phase of growth. what does this suggest?

A

that optimal individual strategy is not to enter persistence

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10
Q

persister state is an alturistic behaviour benefiting the kin. what is meant by the term kin?

A

organism favours genetically related individuals over non-related organisms in social behaviours

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11
Q

if the whole bacterial population was killed by a lethal factor, what cells would remain and what would they do?

A

persister cells would remain
they would propagate genome with their kin
are these cells thinking??

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12
Q

are all cells equal?

A

no

when looking at individual cells you may have low/medium/high producers

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13
Q

when would evaluating if all cells are equal become problematic?

A

when looking at big cultures

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14
Q

if all cells in a bacterial population are genetically identical, how are persister cells produced?

A

by a stochastic process (random)

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15
Q

name the 2 process involved in mechanism of persistence

A

stochastic fluctuation

controlled and regulated mean of expression

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16
Q

what does stochastic fluctuation refer to in mechanism of persistence?

A

happens in level of specific persister proteins

17
Q

what does controlled and regulated mean of expression refer to in mechanism of persistence?

A

happens in specific persister proteins depending on density of population

18
Q

what influence does the environment have on stochastic fluctuation?

A

the environment sets a baseline for stochastic fluctuation

19
Q

why would a cell be in growth arrest?

A

something is inhibiting essential cellular processes eg DNA replication, protein synthesis

20
Q

what could be causing inhibition of essential processes of cells leading to persister cell formation?

A

toxins

environmental cues leading to toxin release

21
Q

what are toxin antitoxin systems?

A

colocated on plasmids (ineffective complex) or chromsome on gene locus (locus = toxin and antitoxin gene)
constant fluctuation
cellular proteases controlling the environment
environmental factors

22
Q

what would cause the degradation of the toxin-antitoxin system?

A

elevated proteases

23
Q

what happens if a toxin antitoxin where to become degraded due to elevated proteases?

A

toxin would be liberated which would initiate growth arrest

24
Q

suggest why the protease wouldnt degrade the toxin

A

secondary structure of the toxin could be preventing the protease from degrading it

25
Q

when is quorum sensing more active?

A

in higher density populations

26
Q

what impact does quorum sensing have on persister cells?

A

quorum sensing produces a higher proportion of persister cells in a bacterial culture

27
Q

suggest a reason why antibiotics may not work against persister cells

A

they are tolerant to the antibiotics (cope with anitbiotics but antibiotics wont kill them)
have a mechanism for tolerance eg efflux pump

28
Q

is antibiotic tolerance genetic?

A

no

29
Q

are persisters in biolfims able to regrow after cessation of antibiotic therapy?

A

yes

30
Q

why is there no commercial driver to treat persister cells?

A

FDA only approve antibiotics for actively growing cells

31
Q

what is the impact of antibiotic treatment on persister cells?

A

serially reducing the concentration of antibiotic gives fewer persister cells with each round of treatment