Microbiota Flashcards

1
Q

Microbiota

A

The microorganisms that typically inhabit a specific environment

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2
Q

Microbiome

A

The totality of microbes, their genomes and environmental interactions in a defined environment

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3
Q

Dysbiosis

A

Microbiome imbalance

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4
Q

Gut microbes

A

Involved in immune system regulation, remove toxins and carcinogens, crowd out pathogens, improve intestinal functions and gut brain links

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5
Q

HMP

A
  • Determine whether individuals share a core human microbiome
  • Can changes in the human microbiome be correlated with changes in human health
  • Develop new technological + bioinformative tools needed to support the HMP
  • Address the ethical, legal and social implications raised by human microbiome research
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6
Q

Microbiome analysis

A
  • 16S rRNA sequencing
    All bacteria have a 16S subunit of ribosomes
    It contains both highly conserved and highly variable regions, that can be used to identify taxonomic groups
    Useful for defining the composition of the microbiota
  • Metagenome sequencing
    Whole genome shotgun sequencing of the microbiome
    Identify the repertoire of functions and pathogens present within the microbiome
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7
Q

Microbial diversity in the human microbiome

A

178 HMP-sequenced genomes present

  • 2 kingdoms
  • 9 phyla
  • 18 classes
  • 24 orders
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8
Q

The gut microbiome

A
  • The most heavily colonised organ in the human body is the GI tract
  • Strict anaerobes outnumber faculatative aerobes and aerobes

The gut microbiota is dominated by 2 phyla

  • Bacteroidetes
  • Firmicutes
  • It is estimated that the human gut contains ~ 500 - 1000 bacterial species
  • Bacterial abundance increases as we progress from the stomach to the colon
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9
Q

Obesity and gut microbiome

A
  • Obesity was associated with a large shift in the relative abundance of the taxa present
  • A 50% reduction in Bacteroidetes + a significant increase in Firmicutes
  • Obese = more Firmicutes
    Better at harvesting energy
  • An ‘obese microbiome’ promoted weight gain when transplanted to a germ-free mouse
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10
Q

IBD

Crohn’s disease

A
  • Nod2 is an intracellular sensor for bacterial peptidoglycan
    It is trying to find the microbes in you to upregulate the innate immune system
  • Nod2 function is required for optimal defensin expression which is an important antimicrobial peptide, a critical component of the innate immune system
  • Nod2 is a function which is required for optimum defensin expression in individuals
  • Defensins are important antimicrobial peptides, a critical part of the innate immune system
  • 3 polymorphisms of Nod2 associated with CD, each polymorphism results in reduced activation of NF-kB in response to bacterial peptidoglycan
    There is a higher incidence of adhesive or invasive E.Coli in patients with dysfuntion in Nod2
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11
Q

CD vs healthy

A

DNA from faecal samples of healthy individuals and CD individuals have been looked at
A change in microbiome

Is there a function of the microbes which is inducing or reducing an individuals likelihood of having CD?
- Faecalibacterium is an anti-inflammatory commensal bacterium
It is promoting anti-inflammatory cytokines and inhibiting pro-inflammatory conditions
Decreasing inflammation in CD individuals
Not found in not CD patients

An anti-inflammatory gut organism such as Faecalibacterium might be an effective probiotic treatment of CD

Eradication therapy targeted against ‘harmful’ components of the microbiota Eg. H. pylori

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12
Q

Disease

A

A condition that impairs normal tissue function

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13
Q

Infection

A

An infection results when a pathogen invades and begins growing within a host
Disease results only if and when, as a consequence of the invasion and growth of a pathogen, tissue function is impaired

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14
Q

Pathogen

A

An organism that is capable of causing disease

It is a disease causing agent in a susceptible host

A true pathogen is an infectious agent that causes disease in virtually any susceptible host

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15
Q

Pathogenicity

A

Pathogenicity is defined by the capacity of a microbe to cause damage in a susceptible host
It is a discontinuous variable
It is dependent on host variables

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16
Q

Virulence

A

It is a continuous variable that is defined by the amount of damage or disease that is manifest

Median infective dose (ID50)- the amount of pathogenic microorganisms that will produce a 50% infection of the test subjects

Median lethal dose (LD50)- the quantity of an agent that will kill 50% of the test subjects

17
Q

What can influence the ID50 and LD50 of a pathogen

A
  • Host
  • Immunological status
  • Physiological status
  • Route of infection
18
Q

Koch’s molecular postulates

A
  • Gene under investigation should be associated with pathogenic members of a pathogenic spcies
    The gene in question should be found in all pathogenic strains of teh species but be absent in non-pathogenic strains
  • The gene which causes virulence must be expressed during infection
  • Specific inactivation of the gene associated with teh suspected virulence trait should lead to a measurable loss in pathogenicity of virulence
    Virulence of the microorganism with the inactivated gene must be less than that of the microorganism with the inactivated gene must be lesss than that of the unaltered microorganism in an appropriate animal model
  • Allelic replacement of the mutated gene should lead to restoration of pathogenicity
19
Q

Incidence

A

The number of new cases of a disease in a given area or population

20
Q

Prevelance

A

The total number, new and already existing

21
Q

Major adherence factors

A

Capsule layer: E.Coli

Adherence proteins: Streptococcus pyogenes, M protein
Neisseria gonorrhoeae, Opa protein

Lipoteichoic acid: Streptococcus pyogenes

Fimbrae/ pili: Neisseria gonorrohoeae, pili
Salmonella, type I fimbriae
E.Coli, fimbriae

22
Q

Type of exotoxins

A
  1. Cytolytic enzymes- they work by attacking cell constituents, causing lysis
  2. A-B toxins- Unit B binds to the cell receptor and allows A to cross the membrane
23
Q

Type of exotoxins

Cytolytic enzymes

A
  • Toxins that lyse red blood cells are called hemolysins

- Staphylococcal a-toxin kills nucleated cells and lyses erythrocytes

24
Q

Type of exotoxins

A B toxins

A

Eg. Diptheria toxin, tetanus toxin, botulinum toxin and shiga toxin

25
Q

Type IV secretion system

A
  • The type IV secretion system of gram negative bacteria: exchange of genetic material with other bacteria
26
Q

Mucous membranes

A
  • Bathed in antimicrobial secretions
  • Contain MALT
  • Antimicrobial peptides don’t target own cell membrane as they are not negatively charged
27
Q

Defensins

A

Antimicrobial peptides
- They are found in neutrophils, Paneth cells and epithelial cells

Cationic peptides
Eg. Cathelicidin, produced by a variety of cells
Neutrophils and respiratory epithelial cells
They make pores in membranes

28
Q

Bacteriocins

A

Peptides produced by the normal bacteria
- They interfere with membranes and form pores
- Degrade DNA and RNA
Eg. Colicins from E.Coli
Sakacins from lactobacilli

29
Q

Type III secretion system

A
  • It is a protein found in some gram negative bacteria
  • It is used as a probe to detect the presence of eukaryotic organisms and secrete proteins to infect them
  • The effector proteins are secreted from the bacterial cell into the host cell
    Eg. Salmonella
30
Q

Effector proteins

A
  • Proteins secreted by pathogenic bacteria using a type III or IV secretion system
  • Usually help a pathogen invade host tissue and suppress the immune system
  • They are normally critical for virulence
    Eg. Yersinia pestis, the removal of the T3SS can leave the bacteria avirulent
31
Q

NF-kB

A
  • A protein complex that controls transcription of DNA, cytokine production and cell survival
  • It regulates the immune response to infection
32
Q

Type I pili

A
  • They attach to mannose receptors
33
Q

Infective and Lethal dose

A

The infective dose can change with how it enters the body

34
Q

Pathogenic E.Coli

A
  • Uropathogenic E.Coli is responsible for roughly 90% of UTI
  • They use fimbriae to bind urinary tract urothelial cells
  • These adhesins specifically bind D-galactose moieties
  • They produce alpha and beta hemolysins
35
Q

Lactobacillus

A
  • Gram positive
  • Facultative anaerobe
  • Non spore forming
  • In the lactic acid bacteria group
36
Q

E.Coli

A
  • Gram negative
  • Facultative anaerobe
  • Rod shaped
  • Commensal in gut and benefit hosts by producing vitamin K2

VIRULENCE FACTORS

  • adhesins, P fimbriae
  • mannose resistant adhesins
  • type 1 fimbriae
  • hemolysin
  • K capsule
37
Q

Medically relevant gram negative cocci

A
  • Neisseria gonorrhoeae
  • Neisseria meningitidis
  • Moraxella
  • Haemophilus
38
Q

Medically relevant gram negative bacilli

A
  • Klebsiella pnemoniae
  • Legionella pneumophila
  • Pseudomonas aeruginosa
  • E.Coli
  • Enterobacter
  • Helicobacter pylori
  • Salmonella
39
Q

Haemophilus

A
  • Gram negative

- Facultative anaerobe