PMI02-2007/8 Flashcards

1
Q

What is pathogenicity?

A

Ability of a microbe to cause disease, discrete (yes/no)

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2
Q

What is virulence?

A

Degree of pathogenicity of an organism, continuous (spectrum)

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3
Q

What are virulent bacteria?

A

Bacteria that usually cause disease when they infect a host

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4
Q

What is a virulence factor/gene?

A

Bacterial component/gene only involved in pathogenesis

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5
Q

What is a housekeeping gene?

A

Gene involved in all aspects of a bacterium’s life

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6
Q

List Koch’s Postulates.

A
  1. Pathogen occurs in every case of the disease and distribution corresponds to that of lesions observed
  2. Pathogen does not occur in healthy subjects
  3. After isolated and repeated growth in pure culture, pathogen can induce disease in susceptible animals
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7
Q

Why do Koch’s Postulates not apply to HIV?

A

Cannot be grown in pure culture (virus)

Poor animal models

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8
Q

Why do Koch’s Postulates not apply to Helicobacter pylori?

A

Present in healthy people

Poor animal models

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9
Q

Why do Koch’s Postulates not apply to Streptococcus mutans?

A

Present in healthy people

Not the sole cause of dental caries

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10
Q

Why do Koch’s Postulates not apply to Chlamydia?

A

Bacterium cannot be grown in pure culture

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11
Q

Why do Koch’s Postulates not apply to Diphtheria?

A

Bacterial distribution does not match lesions (systemic disease but organism only found in throat)

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12
Q

Why do Koch’s Postulates not apply to Mycobacterium tuberculosis?

A

Found in healthy (asymptomatic) people (1/3 of pop)

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13
Q

List the Molecular Koch’s Postulates.

A
  1. Disease phenotype should be associated significantly more often with the pathogenic organism than with a non-pathogenic strain
  2. Specific inactivation of the gene(s) associated with the suspected virulence trait should lead to a measurable decrease in virulence
  3. Restoration of full pathogenicity should accompany replacement of the mutated gene with the wild-type original
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14
Q

What are virulence genes often encoded on and why is this beneficial for microbes?

A

Mobile genetic elements

Can be swapped between micro-organisms

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15
Q

Give an example of a mobile genetic element.

A

Plasmid

Transposon

(Bacteriophage)

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16
Q

What is the main benefit of virulence genes for a microbe?

A

Improves competitive fitness advantage in host

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17
Q

What are pathogenicity islands?

A

20-50 genes with low G/C ratio found in genome

Often flanked by mobile elements so can be swapped in their entirety

Encode toxin gene systems and other virulence factors

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18
Q

What virulence genes are often found in plasmids?

A

Adhesins

Antibiotic resistance

Toxins

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19
Q

Why do bacteria adhere to surfaces?

A

Prevent rapid clearance/protection

Gain a source of nutrients

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20
Q

What three factors are usually required for a bacterium to cause infection?

A

Transmission

Adherence

Invasiveness (sometimes)

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21
Q

How could a microbe be transmitted?

A

Inhalation

Ingestion

Inoculation (needles, skin contact, insects)

Fomite route

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22
Q

What is fomite transmission?

A

Breathing/coughing/sneezing out droplets onto a surface and someone else touching that surface

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23
Q

What cellular structures can be used by bacteria to adhere to a surface?

A

Flagellae

Fimbriae

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24
Q

What are found within flagellae and fimbriae which aid adhesion?

A

Specialised surface proteins involved in:

  • direct attachment
  • signalling to eukaryotic cell to trigger further adhesion or ingestion
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25
What qualities of a microbe can adhesion affect?
Virulence Tissue tropism (what it can infect)
26
Is adhesion always linked to virulence? Why?
No Long-term commensals need to adhere to surfaces too
27
What does adhesion of a bacterial to a cell/surface cause?
Change in gene expression within bacteria Induction of eukaryotic intracellular signalling = changes in gene expression and production of compounds (eg antimicrobial markers, adhesion proteins)
28
What is colonisation?
Presence of micro-organisms without accompanying disease
29
What is infection?
Presence of micro-organisms resulting in disease
30
Describe the changes from contamination to infection.
Initial contamination is just the beginning of colonisation, bacteria not always bound Become resident micro-organisms on adhesion = colonisation; can stay here or progress further Division and invasion into deeper tissue = critical colonisation Gross changes in tissue and host = infection
31
How can bacteria obtain nutrients from a host?
Soluble waste products or host cell not taking up some nutrients Released from host cells through damage
32
What are the two options for a pathogenic bacterium to survive in a host?
Evade immune system Oppose immune function
33
What is superoxide dysmutase used for?
By microbes to prevent phagocytosis/damage by oxygen radicals
34
What is the benefit of being invasive for a microbe?
Penetrate mucosal layers and establish at systemic sites
35
What is septicaemia?
When a bacterial infection enters the bloodstream
36
What factors can aid the invasiveness of an organism?
Secretion of bacterial enzymes Anti-phagocytic factors Toxins that control host cell uptake mechanisms
37
Give an example of a bacterial enzyme that can aid the invasiveness of an organism.
Strep. pyogenes = collagenases Staph. aureus = proteases Haemophilus leucocidins = coagulases
38
Give some examples of anti-phagocytic factors that aid the invasiveness of an organism.
Capsule to prevent phagocytosis (Strep. pneumoniae) M proteins by Group A Streptococci prevent antibodies binding Fc binding proteins to prevent effector functions Leukotoxins to kill macrophages
39
Give an example of an obligate intracellular organism.
Some bacteria: - Chlamydia trachomatis - Rickettsia prowazekii - Mycobacterium leprae All viruses
40
Give an example of a facultative intracellular bacteria.
Salmonella Mycobacterium tuberculosis Legionella Listeria
41
What is a facultative intracellular bacteria?
Bacterium that can survive within or outside of a cell Often have intracellular phases of transcytosis
42
What cell invasion mechanisms do intracellular bacteria have?
Phagocytosis and escape of phagosome Inducing macropinocytosis or endocytosis by: - interaction of invasins with host receptors to control actin - injection of bacterial proteins into cell - complex interactions between toxins and proteins
43
What organism causes typhus?
Rickettsia prowazekii
44
What does Mycobacterium leprae cause?
Leprosy
45
Describe the possible life of a dimorphic intracellular bacterium.
Starts as infectious and metabolically inert elementary body Reorganises itself within phagosome to form a non-infectious and metabolically active reticulate body Multiplies and leaves cell to repeat
46
Describe Rickettsiae bacteria.
Gram-negative bacilli Arthropod-borne Replicates in cytosol of host endothelial cells after escaping phagosome Uses host's actin to escape cell
47
What common features of obligate intracellular bacteria?
Long generation time as not facing as many environmental pressures Small size and small genome (can use host mechanisms) Require exogenous energy supply May infect non-phagocytic cells Protected from lysosomal degradation Use own expression and replication mechanism so not completely dependent on host No environmental reservoir (acquired from other hosts) Cannot be grown by standard bacterial culture techniques so difficult to study
48
What are the advantages of intracellular invasion for a bacterium?
Immune evasion Easily carried around body Obtain nutrients from host Smaller genome (500-1000 genes vs 1500-6000) - "reductive evolution"
49
What is reductive evolution?
Intracellular bacteria lose genes for metabolic pathways as they can rely on host mechanisms Not wasting resources Adaptation to a defined ecological niche
50
Describe pyogenic inflammation.
Acute fever/increased body temperature Recognition of pathogen by innate immune system causes: - release of large amounts of cytokines - neutrophil and macrophage recruitment - opsonisation and bacterial killing Massive reactions may lead to shock
51
What organisms may cause pyogenic inflammation?
Streptococcus pyogenes Streptococcus pneumoniae Staphylococcus aureus
52
Name an organism that causes granulomatous inflammation.
Mycobacterium tuberculosis
53
What is a cytokine storm?
Overactivation of a healthy immune system leading to massive production of cytokines Surge in pro-inflammatory cytokines followed by surge in anti-inflammatory cytokines Usually multiple surges; leads to tissue damage, multiple organ failure, shock and death
54
What are the main cytokine participants in a cytokine storm?
TNF-α IL-6 IL-1
55
In what conditions are cytokine storms mainly seen?
Sepsis and septic shock Viral pneumonias
56
What group of microbes use molecular mimicry to induce a harmful antibody response?
Group A β-haemolytic streptococci
57
What are superantigens?
Antigens that inappropriately, excessively activate the immune response leading to shock
58
What is endotoxin?
Membrane structure/toxin associated with Gram-negative organisms, a type of PAMP LPS Heat-stable and poorly antigenic but triggers a strong innate immune response leading to shock and fever
59
What is an exotoxin?
Pore-forming or surface-acting or intracellular toxin
60
Describe the structure of endotoxin.
Lipid A core with 3 polysaccharide regions Polysaccharide region split into inner and outer cores O antigen, a repeating motif of polysaccharides, may protrude from the outer core
61
What is smooth LPS?
LPS/endotoxin with a long O antigen Gives shiny colonies
62
What is semi-rough LPS?
LPS/endotoxin with a very short O antigen Gives slightly matte colonies
63
What is rough LPS?
Damaged LPS/endotoxin with no O antigen Sometimes increases toxicity
64
How does LPS trigger strong innate immune responses?
Lipid A (of LPS) complexes with LPS Binding Protein (LBP) Macrophage surface complex (TLR4, CD14 and MD2) recognises LBP Triggers signalling in macrophage = cytokine storm, iNOS activation (vasodilation) and inflammation
65
What is endotoxinaemia?
Presence of LPS/endotoxin in blood
66
What are the possible different actions that membrane-acting exotoxins can have?
Enzymatic (digestion of membrane constituents) Pore formation Detergent-like action Perturb signalling
67
What is the enzymatic membrane-acting toxin?
Phospholipase used by C.perfringens, Listeria, C.albicans
68
What size are the pores formed through action of membrane-acting exotoxins and which enzymes may be involved?
Small or large pores = 7-30 subunits E.coli = α-haemolysin S.pyogenes = streptolysin O S.pneumoniae = pneumolysin
69
Describe the pore formation action by membrane-acting toxins.
Toxins associate with a particular receptor in the membrane (may be protein or cholesterol) Causes polymerisation of subunits (toxin + receptor) Undergo conformational change after polymerisation to protrude through membrane
70
How can a membrane-acting toxin have a detergent-like action?
Hydrophobic protein toxin associates with hydrophobic tails of membrane = disruption
71
Which types of membrane-acting toxins perturb signalling?
Stable toxin Specific proteases Superantigens
72
What is a stable toxin?
Small, cysteine-rich peptide produced by Enterotoxigenic E.coli (ETEC) Heat-stable Binds to extracellular domain of guanylyl cyclase C as it is similar to the natural ligand guanylin Leads to inappropriate activation of intracellular domain to produce cGMP from GTP Leads to efflux of Cl- and prevents Na+ influx => osmotic diarrhoea as water is drawn out of cells
73
How can membrane-acting toxins act as superantigens?
Associate with MHC class II on APCs and cross-link it to a vβ region of a TCR of a non-specific T cell Causes non-specific activation of T cells (polyclonal activation)
74
Give an example of a membrane-acting toxin that can act as a superantigen.
TSST-1 from S.aureus (leads to toxic shock syndrome)
75
What do intracellular toxins do?
Bind cell surface, cross membrane and have enzymatic activity in the cell (may be injected in directly)
76
What are the different parts of an AB toxin?
A fragment is active B fragment is involved with binding
77
Give an example of a neurotoxin.
Botulinum toxin Tetanospasmin
78
What do neurotoxins do?
Attack signalling between nerve cells or vesicle docking in synapse Associated with zinc proteases
79
What does tetanospasmin do?
Prevents postsynaptic inhibitory molecules from binding so signal never turns off
80
What does botulinum toxin do?
Prevents release of excitatory transmitter so no signal is generated Attacks syntaxin, synaptobrevin, SNAP-25
81
What are the symptoms of tetanus?
Restlessness Headaches Irritability Muscle spasms, eg lockjaw
82
What are the symptoms of botulism?
Muscle weakness Excess sweating Dry mouth Parkinson's type symptoms
83
Describe the diphtheria toxin.
AB toxin - additional T region as part of B region involved in endosome insertion/toxin translocation T region = series of α-helices with negatively charged loops between Acidic conditions in endosomes = H+ associate with negative loops which allows the α-helices to closely associate with the membrane and escape endosome Blocks EF-2 involved in peptide extension (translation) by adding ADP ribose (from NAD) => ADP-ribosylase enzyme
84
How is diphtheria treated/managed?
Vaccine Antitoxin Antibiotics Rest
85
What are the symptoms of diphtheria?
Inflamed throat Fever Diphtheric membrane in throat
86
Give examples of ADP-ribosylating enzymes and what they do.
Diphtheria toxin and P.aeruginosa ETA = modifies EF-2 Cholera and pertussis toxins, E.coli labile toxin = modify signalling proteins
87
Name some non-toxin diseases and their causative agents.
Plague = Yersinia pestis Typhoid = Salmonella typhoid Shigellosis = Shigella flexneri
88
How do non-toxin diseases cause damage?
Use secretion systems to inject toxins directly into cells
89
What did the type III secretion system evolve from?
Flagellae
90
What did the type IV secretion system evolve from?
Pili
91
What did the type VI secretion system evolve from?
Bacteriophages
92
Describe the type III secretion system.
Resting state = coiled, compressed protein complex spanning the membrane bilayer Contact with eukaryotic cell causes decompression and protrusion of system into cell to allow toxin secretion into it
93
Name a genus that uses type III secretion systems.
Yersinia
94
Describe how the type VI secretion system arose.
Viral DNA injected into bacteria Bacteriophage incorporated into inner membrane and genome Over time, these mutate and can be used by the target organism to inject their own toxins into a host
95
Give an example of an organism that uses type VI secretion systems.
Vibrio cholera
96
Why are toxins so potent?
Target key cellular components (membrane, protein synthesis, signalling) Usually enzymatic action so can be used repeatedly