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MBBCh 2- HAEM2000A > v. Dysbiosis and Disease + Microbes and The Biofilm Concept > Flashcards

v. Dysbiosis and Disease + Microbes and The Biofilm Concept Flashcards

1
Q

What is Dysbiosis?

A

Dysbiosis: Change in the microbiota, no longer the normal balance between the different types of organisms and different proportions of each species.

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2
Q

What are the effects of dysbiosis? (3)

A
  • Loss of overall diversity
  • Change in the ratios of the major phyla
  • Bloom of a specific bacterium, especially one with the potential to cause damage
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3
Q

NOTE: Do not know whether the change in the microbiota that is associated with a disease is either the CAUSE of the disease or an EFFECT of the disease being present. THERE IS ASSOCIATION OF CHANGES IN THE MICROBIOTA WITH SPECIFIC DISEASES. So far it cannot be said conclusively that if you change the _____, you will stop the disease.

A

microbiota

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4
Q

Some of the associations between gut dysbiosis and disease: MAJOR CHANGE IN THE MICROBIOTA IS ASSOCIATED WITH THESE DISEASES OF VARIOUS ORGANS.

  • Brain disorders:
A

Autism, Depression, Stress, Stroke (atherosclerosis)

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5
Q

Some of the associations between gut dysbiosis and disease: MAJOR CHANGE IN THE MICROBIOTA IS ASSOCIATED WITH THESE DISEASES OF VARIOUS ORGANS.

  • Lung:
A

SCFAs produced by the microbiota supress the immune response in allergic Asma.

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6
Q

Some of the associations between gut dysbiosis and disease: MAJOR CHANGE IN THE MICROBIOTA IS ASSOCIATED WITH THESE DISEASES OF VARIOUS ORGANS.

  • Liver:
A

Non-alcoholic fatty liver disease(NAFLD) and Non-alcoholic steatohepatitis (NASH)

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7
Q

Some of the associations between gut dysbiosis and disease: MAJOR CHANGE IN THE MICROBIOTA IS ASSOCIATED WITH THESE DISEASES OF VARIOUS ORGANS.

  • Skin:
A

Atopic dermatitis, Psoriasis

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8
Q

Some of the associations between gut dysbiosis and disease: MAJOR CHANGE IN THE MICROBIOTA IS ASSOCIATED WITH THESE DISEASES OF VARIOUS ORGANS.

  • GIT:
A

Inflammatory bowel disease (Ulcerative colitis, Crohn’s disease)

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9
Q

Some of the associations between gut dysbiosis and disease: MAJOR CHANGE IN THE MICROBIOTA IS ASSOCIATED WITH THESE DISEASES OF VARIOUS ORGANS.

  • Whole body:
A

Metabolic syndrome (Diabetes T2, atherosclerosis – increased blood pressure)

Systemic lupus erythematosus: Autoimmune disease (Upregulation/Lack of inhibition of IS is contributing to the increased incidence of these diseases)

Undernourishment: Children chronically malnourished even with correct feeding for extended periods (incorrect gut flora).

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10
Q

Antibiotics are one of the cornerstones of modern medicine but WE ARE USING THEM TOO MUCH AND INCORRECTLY!
Effects on the individual: (4)

A
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11
Q

Maintaining our Gut Microbial ‘Lawn’:

How is this maintained? (3)

A
  • Probiotics
  • Prebiotics
  • Bacteriotherapy
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12
Q

Maintaining our Gut Microbial ‘Lawn’:
- Probiotics:

A
  • Probiotics: SEEDS. Live microorganisms that, when administered in adequate amounts,
    confer a health benefit for the host.
    Organisms known to be a part of the healthy gut microbiota. Only contain about 15 different organisms YET we need about 500-1000 different organisms in our gut. Cannot just buy probiotics to completely re-establish you microbiota.
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13
Q

Maintaining our Gut Microbial ‘Lawn’:
- Prebiotics:

A
  • Prebiotics: FOOD/FERTILIZER. Non-digestible food ingredients that, when consumed in sufficient amounts selectively stimulate the growth/activity of a limited number of microbial genera or species in the gut that confer(s) health benefits to the host
    Intense forms of fibre – Need diversity of fibres (eat as much variety in our diets as possible to feed the greatest amount of different bacterial species as possible).
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14
Q

Maintaining our Gut Microbial ‘Lawn’:
- Bacteriotherapy:

A

Transplantation of the entire ecosystem (Faecal transplants) Encapsulated versions are being developed. Take note of the different areas within the GIT and how not all the species of bacteria are represented in faceal matter due to the distribution in mucosal folds. Thus, even if you use a faecal transplant, you may not necessarily regenerate all the organisms that the original donor had.
Faecal transplants are very useful, especially for patients who have chronic gut infections (avoid further doses of antibiotics).

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15
Q

Establishment of microbiota: (2)

A
  1. FOOD IS MEDICINE – MICROBIOTA EFFECT
    The discovery of the microbiota and effects on the body is like the discovery of a whole new organ that requires treatment and care.
  2. GOOD MICROBIOTA = GOOD HEALTH AND MENTAL STATE
    - Mom via vaginal organism
    - Correct feeding/nutrition via breast milk
    - Balanced diet high in variety of fibres.
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16
Q

The Biofilm Concept:
- September 17, 1683: _____ ____ ______ gives us reason to brush & floss
- Scraped plaque from his own ____
- Observed _______ under his primitive microscope
- It’s the first known description of a ____

A

Antoine van Leeuwenhoek
teeth
“animalcules”
biofilm

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17
Q

What is a biofilm? (4)

A
  • Accumulations/aggregate of microorganisms of mono or poly microbial aggregates
  • Enclosed within a self-produced matrix of extracellular polymeric substances (EPSs)
  • The microorganisms produce the EPS (slime) for protection
  • Irreversibly associated to each other and/or to a surface
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18
Q

What is a biofilm:
- Common misconception :
- Reality:

A
19
Q

What is the morphology of biofilm? (2)

A
  • Biofilms have varied morphologies (seen under SEM) which depend on the constituent
    bacteria and the conditions under which the biofilm was formed.
  • A: Pseudomonas aeruginosa which is isolated attached to a glass surface.
    C: Staphylococcus aureus biofilm growing in vivo
20
Q

Biofilm structure:
- The structure of the extracellular polymeric substance (EPS) matrix of biofilms is composed: (3)

A

o One or more of extracellular polysaccharides (exopolysaccharide)
High molecular weight polymers that are composed of sugar residues and are
secreted by bacteria into the surrounding environment.
o DNA
o Proteins

21
Q

Biofilm structure:

  • ______ in the biofilm allow for water, air and nutrients to get to all parts of the structure.
  • Biofilms may form on ____ or _____ surfaces
  • Present in natural, industrial, & hospital settings (living tissues, medical devices - catheter)
A

Channels
Biotic
Abiotic

22
Q

What is a pre-requisite of biofilm?

A

Pre-requisite of biofilm formation is that bacteria should get close enough to a surface. As bacteria approaches a surface, several forces will act (both attractive and repulsive forces). When the bacteria is 10/20 nm away from the surface, the negative charges on the bacteria is repelled by the negative charges on most environmental surfaces. This repulsion may be overcome by attractive Van Der Waal forces between the bacterial cell and environmental surface, with the use of fimbria and flagella – Providing mechanical attachment to surface.

23
Q

How is biofilm formed: 5 Major stages of biofilm development:

A
  1. Dispersion:

Occurs because there is lack of nutrition due to growing population or due to intense competition among different bacterial species within the biofilm. May disperse as a whole or a specific part of the biofilm. When dispersed as a whole, they will form another biofilm

24
Q

What are the reasons for biofilm formation? (2)

A
  • Enhance the tolerance of bacteria to harsh environmental conditions.
  • Resistance to antibiotics & host immune system
25
Q

Reason for biofilm formation:
- Enhance the tolerance of bacteria to harsh environmental conditions.

How does this process occur? (2)

A

o Bacteria can avoid being washed away by water flow or blood stream by simply attaching to a surface or tissue.

o Cells in biofilms are about 1000 times more resistant than their planktonic

26
Q

Reason for biofilm formation:
- Resistance to antibiotics & host immune system

What are the factors affecting this? (6)

A
27
Q

Communication/Signalling in biofilm formation: Quorum sensing

  • Quorum sensing:
A
  • Quorum sensing: Cell-cell communication process that regulates gene expression at high cell density.
28
Q

What is the process of Quorum sensing? (7)

A
29
Q

Quorum sensing (QS):
- Chemical signals produced by _______ cells are not concentrated enough to cause changes in genetic expression
- The EPS in biofilms holds cells in close _______ & allows concentrations of signal molecules to build up in sufficient quantity to effect changes in cellular _______
- Microorganisms will only activate some genes when they are able to sense (via cell signalling) that their population is large enough to make it advantageous and/or “safe” to initiate that genetic activity.
Do not just upregulate certain genes whenever, they will sense a need for something specific and will produce it when it is advantageous or safe to initiate specific _____ _______.
- Example: Some bacterial pathogens will not produce ______ until they sense that an adequate population has been established to survive host defences.

A

planktonic
proximity
behaviour
genetic activity
toxins

30
Q

Biofilms in Infectious Diseases:
- About 65% of all bacterial infections are associated with bacterial biofilms
- Two types of medically important biofilms : (2)

A
31
Q

Biofilms & Hospital Acquired Infections:
Main nosocomial infections associated with biofilms: (4)

A
32
Q

Biofilm-related disease example: Cystic fibrosis (CF)
- CF in the lung causes the formation of thick and sticky mucus, which blocks _____ and makes it hard for patients to breath.
- 80% of CF patients are chronically infected by _______

A

airway
P. aeruginosa

33
Q

Biofilm-related disease example: Cystic fibrosis (CF):

  • Medical instruments, devices and tools can also be ______ with P. aeruginosa.
  • Several cases of hospital acquired P. aeruginosa infections have been reported, but unfortunately, there are not many good antibiotics that are available for treating ______ P. aeruginosa infection.

Because bacterial infection is occurring in a biofilm it is difficult for antibiotics to penetrate into the infection AND transfer of ______ ______ genes.

A

contaminated
refractory
antibiotic resistant

34
Q

Biofilm-related disease example: Cystic fibrosis (CF):

  • For patients who are infected with P. aeruginosa , _______ treatment often relieves the symptom of the infection but not necessarily cures the infection.
  • The lack of complete cure is mainly due to P. aeruginosa biofilms that act as _____ for disease recurrence (persister cells).
A

antibiotic
reservoir

35
Q

Biofilm-related disease example: Cystic fibrosis (CF):

  • Beyond acting as disease reservoirs, the components of biofilms, such as the major ______ of P. aeruginosa matrix (alginate), are virulence factors. For example, alginate can cause lung damage.
  • Mucoid variant (large colony) will overproduce the alginate (virulence factor in the matrix of the biofilm). Mucoid _____ are only found in patients with chronic biofilm infection. Thus, ______ is a biofilm-specific antigen.
    Nonmucoid variant (small colony)
A

polysaccharide
colonies
alginate

36
Q

Device-related Case Scenario:
- Mr. Kevin Naidoo is a 37 y/o with a history of extensive small bowel resection for Crohn’s disease.
- Presenting complaint:
o 7-day history of low grade fever (mean: 37.8 C) & malaise
o He is receiving long term parenteral nutrition (TPN) that he was taught to infuse
overnight at home via a Hickman intravascular line - On examination (in casualty department):
o Skin around the Hickman line insertion site is red & tender o Pus is oozing from the insertion site
o Now spiking a temperature of 38.6 C & looking very ill
- He is admitted to hospital
- A pus swab and blood cultures are taken for microscopy, culture & sensitivity
- He is started on IV antibiotics

A

READ

37
Q

Management of biofilm-related infections:
- Current approaches: (7)

A
38
Q

Management of biofilm-related infections:
- Novel and future approaches: (6)

A
39
Q

What is a biofilm?

A
  • Biofilms are defined as aggregated microorganism communities attached to surfaces and embedded in a self-produced matrix which is composed of extracellular polysaccharide, DNA and proteins. Combination of sessile and planktonic cells gathered together.
40
Q
  • There are 5 major steps in biofilm formation:
A
  1. Initial reversible attachment
  2. Irreversible attachment
  3. Micro-colony (growth & cell division)
  4. Maturation (production of EPS)
  5. Dispersion.
41
Q
  • The biofilm structure provides the bacteria with the ability to tolerate _____ environmental conditions, resistance to antibiotics and host immune systems, and provides an optimal environment for _______ DNA (plasmid)
  • Various human diseases are related to biofilm. Biofilms play an important role in _____ diseases.
A

harsh
extracellular
dental

42
Q
  • Signalling in biofilm formation: (2)
A

o Bacteria synchronize their gene expression by producing and responding to
autoinducers.

o Quorum sensing regulates biofilm formation in several bacterial species.

43
Q
  • Biofilms in vivo:
A

o The microenvironment in vivo is different from that in vitro.

It is important to investigate biofilms inhibition in vivo in animal models.

MBBCh 2- HAEM2000A (30 decks)

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