Lecture 6 - bacterial persistence and surviving an environment in flux Flashcards

1
Q

Environments that bacteria can grow in

A

Bacteria can pretty much grow in any environment (soil, hot, dry, cold, ice, within and on us)

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2
Q

oxygen is one of the most important ______ factors in both medical and environmental microbiology

A

Abiotic

Abiotic factors refer to non-living physical and chemical elements in the ecosystem.

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3
Q

Aerobic environment

A

Aerobic = high oxygen (atmospheric, 21%)

Aerobes prefer oxic environments

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4
Q

Microaerobic environment

A

Microaerobic = trace oxygen (2-10% or less)

Microaerophiles prefer hypoxic environments

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5
Q

Anaerobic environment

A

Anaerobic = no oxygen (strictly 0%)

Anaerobes prefer anoxic environments
Facultative = change metabolism under oxia (they can adapt)

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6
Q

Host associated environments

A

internal or bacteria dense environments are anaerobic

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7
Q

Soils and oceans as environments

A

decreasing oxygen with increasing depth (oxygen can’t diffuse as far and because of bacterial activity)

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8
Q

Eutrophication

A

High local activity of aerobes can lead to oxygen minimum zones, eutrophication (Eutrophication is when the environment becomes enriched with nutrients. The microbes may use up all the oxygen in the water, leaving none for other marine life. This results in the death of many aquatic organisms such as fish, which need the oxygen in the water to live.)

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9
Q

Flexibility in terms of microbes means

A

the ability to adapt to a wide range of environments

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10
Q

What environment does most microbes inhabit?

A

Relatively few microbes are lucky enough to live in nutrient-rich eutrophic environments. Rather, most inhabit oligotrophic environments - ones in which nutrient levels are low and some live in feast-and-famine environments.

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11
Q

Higher eukaryotes in terms of flexibility

A
Higher eukaryotes (which are hosts for example) = inflexible 
Obligately heterotrophic (e.g. sugars, amino acids, fats) 
Obligately aerobic (oxygen for respiration) 
Ferments transiently and products must be recycled
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12
Q

Bacteria in terms of flexibility

A

Bacteria = flexible
Diverse organic and inorganic electron donors
Oxygen and anaerobic electron acceptors (facultative anaerobe)
Fermentation as terminal, sustained mode of energy generation (even when there is limited processes for respiration to occur)

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13
Q

E. coli in terms of flexibility

A

Numerous substrates for energy generation

Can use greater than 6 alternatives to oxygen for respiration

Can live on trace gases (H2) if no nutrients are available

Flexiblity allows ATP generation when environment changes

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14
Q

Bacteria as recyclers

A

Bacteria are the ultimate recyclers which is part of their flexibility, there is a vast amount of carbon and energy sources that they harness - plant tissue, animal tissue, excretory products - end products, cells of dead bacteria, antibiotics, plastics, heavy metals

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15
Q

Bacteria have diverse _____ _____ for breaking down several polymers into monomers

A

digestive enzymes

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16
Q

Bacteria digestive enzymes are typically

A

Typically bound-in or associated with cell surface to prevent losses to competitors

Releases monomers or shorter oligomers that conserved pathways can use such as glucose, amino acids, fatty acids

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17
Q

Polymers and monomers

A

Polymers are molecules made of monomers such as proteins (monomer =amino acid), DNA (monomer = nucleotides, fats (monomers = glycerol)

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18
Q

What happens if there is not food for bacteria?

A

Bacteria are specialists at growing slowly or not at all - persistence

Still metabolically active

Different to true dormancy i.e. being an endospore (endospore is not only resistant to a variety of stressors but are also metabolically dormant)

Most environments are too nutrient limited to reflect batch culture

Persistence most likely normal state of bacteria in environment

In reality in the environment, bacteria can enter a long term stationary phase which is also known as long term resistance where the bacteria that have survived the death phase have now adapted to growing slowly/if not at all and in this case there is very little cell death but what we can have is spontaneous mutations occur that can create lots of different kinds of strains

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19
Q

R type strategist examples

A

e.g. E.coli, B.subtilis

20
Q

R type strategist

A

Fast growing (TD= minutes)

May use food wastefully

Last ditch strategies during stress: sporulation, “bust and boom”

Dynamic persistence of small subpopulation

Overproduce and those that survive are those that are likely to have entered the persistent state

21
Q

R type strategist TD

A

Fast growing (TD= minutes)

22
Q

K type strategist examples

A

e.g. M.tuberculosis, soil bacteria

23
Q

K type strategist

A

e.g. M.tuberculosis, soil bacteria

Slow growing (TD= days)

Uses food efficiently therefore there is less waste

Survives stress for months-years with less drastic metabolic changes

Bulk of population persists

24
Q

K type strategist TD

A

Slow growing (TD= days)

25
Gram negative vs gram positive
Gram negative cell wall has two plasma membranes separated by a periplasmic space, gram positive has one inner membrane and peptidoglycan layer that is thick
26
current antibiotics
are only effective when a bacterium is growing (log phase) e.g. cell wall synthesis inhibitors and protein synthesis inhibitors
27
Starvation responses induce ....
protective responses to some antibiotics
28
Some antibiotics need...
Some antibiotics need energy to be taken up by bacteria, stationary vs log - Adding nutrients can recover activity However since 1940s its known that some log phase bacteria survive in clinic
29
Persisters
Persisters are bacterial cells identified by their ability to survive exposure to an antibiotic (often multiple antibiotics) even though they do not harbour antibiotic resistance genes. They are non-growing cells that are though to be dormant. Dormancy is central to the hypotheses regatding their antibiotic-tolerant phenotype; in dormant cells, the target of an antibiotic is unavailable to inactive and would be unaffected by the antibiotic. Persisters are of considerable interest for several reasons, including their potential to cause recurrent infections after major antibiotic treatment
30
Antibiotic resistance
Antibiotic resistance = heritable genetic changes allow bacteria to grow Mutate their genes or acquire enzymes but there are changes in DNA therefore are heritable
31
Antibiotic persistance
Antibiotic persistance = non-heritable physiological changes allow survival of a few slow or non-growing cells Something happens during the course of treatment, most of them die off but there is a dynamic subpopulation of cells that grow very slowly can then regrow back to the beginning point when conditions become favourable again
32
What keeps the resistance genes in a population and contributes to the drug-resistant bacteria strains is ...
exposure to the drug
33
What makes treatment time longer in terms of antibiotics?
inability of antibiotics to kill non-growing cells makes treatment time longer
34
Persistence can lead to
resistance
35
Wiping out populations with antibiotics ...
Unlike environmental persistence, although we have the R and K type selection in the environment and population level strategies, when we just wipe out populations with antibiotics it is environmental catastrophe, their responses tend to look a lot more like an R type selection response regardless of the organism
36
Environmental persistence features
Response to fluctuating food and nutrient supplies Different population-level strategies (r/K) Adaptation for long-term survival More time to respond
37
Antibiotic persistance features
Response to an environmental catastrophe (antibiotic killing) Similar population-level strategies Subpopulation of cells stochastically (randomly) preadapted Less time to response
38
responses to stress (3)
stringent response, SOS response, Toxin-antitoxin systems
39
methods of persistance (5)
mutations, stationary phase, antibiotic exposure, vacuoles and biofilms
40
responses to stress purpose
Evidence suggests that in some cases, small sub­ sets of cells in a population of growing cells spontaneously be­ come dormant persister cells, even when nutrients are readily available. These persisters can be thought of as the population’s attempt to prepare for future possible starvation conditions. There is also increasing evidence that persisters arise in response to various triggers, with starvation probably being the most im­ portant.
41
Stringent response
shift in the expression the genes to a survival based response Mediated by molecule (p)ppGpp Stops expensive biosynthetic processes ppGpp is a signaling molecule that functions in a regulatory network called the stringent response. ppGpp is often referred to as an alarmone because it is synthesized in response to many stressors and regulates the activity of numerous genes and proteins so that the cell can survive.
42
SOS response
stress induces DNA repair, also has survival features Both repair and survival responses Mediated by protein RecA
43
Toxin-antitoxin systems
Balancing act with diverse cellular functions Disruption of antitoxin leads to growth inhibition by toxin The toxin when functioning disrupts normal cellular functions, causing growth arrest and the persister phenotype inter­nal, nonsecreted toxin and a cognate antitoxin that prevents the toxin from exerting its effects on the cell. The toxin, when func­tioning, disrupts normal cellular functions, causing growth arrest and the persister phenotype.
44
Hypoxia in terms of persistance and example
gradual depletion of oxygen leads to a stationary phase, slowed growth and persistent phenotypes M.tuberculosis frequently encounters hypoxia in host and intracellular environments Macrophage phaglysosome Granuloma; immune structures forming wall
45
Biofilms
Slimy matrix of various bacteria produced polymers Local depletion of nutrients/oxygen leads to persister cell formation Physical protection from environment combined with antibiotic persistence A mature biofilm is a complex, dynamic community of microorganisms. It exhibits considerable heterogeneity due to differences in the metabolic activity of microbes at various locations within the biofilm; some are persister cells While in the biofilm, microbes are protected from numerous harmful agents such s UV light and antibiotics
46
All forms of persistance cause a shift to form of
energy metabolism that permits survival without growth