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BMS2052 > Current Challenges in Infectious Disease > Flashcards

Current Challenges in Infectious Disease Flashcards

1
Q

How are there different rabies P-protein isoforms?

A

Differing Kozak sequences around start codons that determine the likelihood of the ribosome initiating translation at that site. Results in 5 different P-proteins

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2
Q

Definition

denoting or relating to a cell-produced substance that has an effect on the cell by which it is secreted

A

Autocrine

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3
Q

Definition

A bacterium that is the most common cause of gas gangrene, a lethal infection of soft tissue, especially muscle

A

C. perfringens

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4
Q

Definition

Lyssavirus protein that encapsidates the genome; required for transcription and replication

A

Nucleoprotein (N)

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5
Q

Definition

Lyssavirus protein required for viral assembly and budding

A

Matrix (M)

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6
Q

These type of spores indicate what type of Clostridium?

A

C. tetani

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7
Q

Define

Dysbiosis

A

a term for a microbial imbalance or maladaptation on or inside the body, such as an impaired microbiota

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8
Q
A
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9
Q

What does DNA dependent RNA polymerase do?

A

Transcribes DNA into RNA

aka RNA polymerase

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10
Q

Definition

a toxin produced in or affecting the intestines, such as those causing food poisoning or cholera

A

Enterotoxic

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11
Q

Which rabies proteins help form the Negri Bodies?

A

N and P

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12
Q

Definition

family of proteins, which function as general cross-linkers between plasma membrane proteins and the actin cytoskeleton and are involved in the functional expression of membrane proteins at the cell surface

A

Ezrin

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13
Q

Define

Glycoprotein (G)

A

Lyssavirus protein found on the outside or particle, immunogenic; required for viral entry into host cell

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14
Q

Define

β-catenin

A

a multifunctional protein that plays an important role in the transduction of Wnt signals and in the intercellular adhesion by linking the cytoplasmic domain of cadherin

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15
Q

Define

Ovoid subterminal (OST) spores

A

The ovoid shaped spores that most Clostridium spp., including C. perfringens and C. botulinum have

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16
Q

What makes up the nucleocapsid of the Rabies virus?

A

The nucleocapsid is a Ribonucleoprotein (RNP) - complex composed of RNA and proteins

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17
Q

Define

Adherens junctions (AJ)

A

a cell junction whose cytoplasmic face is linked to the actin cytoskeleton

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18
Q

List the enterotoxic Clostridia

A

C. perfrigens

C. difficile

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19
Q

Definition

the outer surface layer of mature spores

A

Exosporium

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20
Q

Definition

tiny, self-organized three-dimensional tissue cultures that are derived from stem cells

A

Organoid

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21
Q

What form is the Rabies virus genetic material in?

A

Negative sense RNA

(-)ssRNA

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22
Q

How does Rabies virus travel from the bite site to the brain?

A

Retrograde axonal transport along the microtubules of neurons

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23
Q

Which species of Clostridia cause tetanus?

A

C. tetani

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24
Q

Which toxin is responsible for intestinal necrosis seen in C. perfringens?

A

β-toxin

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25
Q

What are the three broad strategies that viruses have to avoid IFN action?

A
  1. General inhibition of host gene expression
  2. Sequestration/masking of PAMPs
  3. Sequestration/modification of signally components
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26
Q

Define

RNA antigenome

A

The complementary strand of RNA from which the genome of a virus is constructed

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27
Q

Which Rabies genes are required for RNA synthesis?

A

N, P and L

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28
Q

List the neurotoxic Clostridia

A

C. tetani

C. botulinum

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29
Q

What are the basic characteristics of Clostridium?

A

Gram-positive rods

Obligate anaerobes

Form heat resistant endospores

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30
Q

Define

Dead-end host

A

a host from which infectious agents are not transmitted to other susceptible hosts

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31
Q

Define

Hydrophobia

A

extreme or irrational fear of water, especially as a symptom of rabies in humans

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32
Q

When is the tetanus toxin released?

A

Released when the bacteria die

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33
Q

How does Rabies virus enter cells?

A

Rabies virus enters by receptor-mediated endocytosis

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34
Q

What are the new C. difficile treatments under consideration?

A
  • Probiotics
  • Intravenous IgG antibodies (containing human anti-toxin IgG)
  • Monoclonal antibodies for passive immunotherapy
  • Passive polyclonal immunotherapy (cow colostrum; egg yolk antibodies)
  • Faecal transplant therapy
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35
Q

Definition

a virus that can be transmitted from bats to humans, causing serious illness

A

Australian Bat Lyssavirus (ABLV)

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36
Q

What do you need to make a modified Rabies virus?

A

Rabies genome

N-protein

P-protein

L-protein

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37
Q

Describe the structure of the Rabies P-protein

A
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38
Q

Define

Clostridium

A

an anaerobic bacterium of a large genus that includes many pathogenic species, e.g. those causing tetanus, gas gangrene, botulism, and other forms of food poisoning

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39
Q

This posture is typical of which type of C. perfringens infection?

A

Type D

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40
Q

Which of the species of Clostridia cause botulism?

A

C. botulinum

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41
Q

Definition

A transmembrane protein that links plasma membranes of adjacent cells together in a Ca2+-dependent manner; aids in maintaining the rigidity of the cell layer

A

E-cadherin

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42
Q

What are Negri Bodies?

A

Membrane-less cytoplasmic inclusions caused by Rabies infection

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43
Q

Definition

The complementary strand of RNA from which the genome of a virus is constructed

A

RNA antigenome

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44
Q

Definition

a contagious and fatal viral disease of dogs and other mammals, transmissible through the saliva to humans and causing madness and convulsions

A

Rabies

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45
Q

Definition

a nucleic acid motif that functions as the translation initiation site in most mRNA (link) transcripts

A

Kozak sequence

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46
Q

Definition

a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum

A

Clostridium botulinum

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47
Q

Definition

Lyssavirus protein required for replication and transcription; also known as RNA-dependent RNA polymerase

A

Large protein (L)

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48
Q

What is the order of Rabies virus genes?

A

N, P, M, G then L

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49
Q

Define

Clostridium tetani

A

the bacteria responsible for the often fatal disease tetanus

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50
Q

Which toxin is responsible for the histotoxic effects of C. perfringens?

A

α-toxin

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51
Q

Define

Encephalitis

A

inflammation of the brain, caused by infection or an allergic reaction

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52
Q

True or False:

Rabies viruses only need one method to disrupt the IFN pathway

A

False

Viruses use many ways to disrupt IFN pathway

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53
Q

What are the three main types of IFN?

A

Type I: IFNα and IFNβ - direct response to infection broad cellular expression and receptors

Type II: IFNγ - immune cells

Type III: IFNλ

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54
Q

Define

Negri bodies

A

eosinophilic, sharply outlined, pathognomonic inclusion bodies (2–10 μm in diameter) found in the cytoplasm of certain nerve cells containing the virus of rabies, especially in pyramidal cells within Ammon’s horn of the hippocampus

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55
Q

What makes up the three main components of the assembled Rabies virus?

A
  1. Nucleocaspid (RNA, N, P, L)
  2. M (at plasma membrane)
  3. G (glycosylated - sugar groups added)
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56
Q

What shape are Rabies viruses?

A

Helical

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57
Q

List the 4 different ways that the rabies P-protein inhibits IFN signalling

A
  1. P binds and prevents nuclear import of STAT1/2
  2. P traffics into nucleus and brings STATs out
  3. Nuclear P3 isoform binds STATs in nucleus and prevents bind to DNA
  4. P3 binds STATs and arrests them on microtubules
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58
Q

Definition

a toxin produced by the bacterium Clostridium perfringens (C. perfringens) and is responsible for gas gangrene and myonecrosis in infected tissues

A

α-toxin

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59
Q

What type of spores do most Clostridium spp. including C. sporogenes and C. botulinum produce?

A

Ovoid subterminal (OST) spores

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60
Q

Define

Mononegavirus infections

A

the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus

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61
Q

What toxins do Type C C. perfrigens infections involve?

A

α and β toxins

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62
Q

Define

Sporulation

A

the formation of nearly dormant forms of bacteria

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63
Q

How many genes do Lyssaviruses encode? What are they?

A

5

N, P, M, G, L

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64
Q

What is the new name for the Clostrdium species?

A

Clostridioides

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65
Q

What does the α-toxin of Clostridia do?

A

Phospholipase

Disrupts host-cell plasma membranes

Extensive destruction of cells and tissues

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66
Q

Define

Anaerobic jars

A

an instrument used in the production of an anaerobic environment. This method of anaerobiosis as others is used to culture bacteria which die or fail to grow in presence of oxygen (anaerobes)

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67
Q

What happens to epithelial cell polarity in C. difficile infection?

A

Completely disrupted

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68
Q

True or False

Both botulism and tetanus can be prevented with a vaccine

A

False

Tetanus has a toxoid vaccine available but botulism has no vaccine available (antitoxin can be used)

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69
Q

Which Rabies protein binds to N-RNA and L (linking them together)?

A

P protein

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70
Q

Definition

relating to or denoting a hormone which has effect only in the vicinity of the gland secreting it

A

Paracrine

71
Q

What causes sporulation?

A

Adverse conditions

72
Q

Define

Anaerobic chamber

A

atmosphere control units designed to be used when working with oxygen sensitive materials, product containment needs, and/or general isolation control

73
Q

The Rabies genome (-RNA) makes _________ (+RNA) in order to make new genomes

A

The Rabies genome (-RNA) makes antigenome (+RNA) in order to make new genomes

74
Q

Define

botulinum neurotoxin (BoNT)

A

a neurotoxic protein produced by the bacterium Clostridium botulinum and related species

75
Q

List the histotoxic Clostridia

A

C. perfrigens

C. septicum

C. sordellii

76
Q

Where does replicaiton of the Rabies viral genome occur?

A

In “liquid” Negri Bodies

77
Q

What are the three groups of pathogenic clostridia?

A

Neurotoxin

Enterotoxix

Histotoxic

78
Q

Oxygen causes Clostridium to do what?

A

Form endospores

79
Q

Definition

a cell junction whose cytoplasmic face is linked to the actin cytoskeleton

A

Adherens junctions (AJ)

80
Q

What conditions often develop following microbiota dysbiosis?

A

Candida

C. difficile infection

81
Q

Which type of Clostridia causes gas gangrene?

A

C. perfringens

82
Q

What function do many IFN stimulated genes (ISGs) have?

A

Antiviral properties

83
Q

Are Rabies viruses enveloped or naked?

A

Enveloped

84
Q

True or False

All strains of C. difficile have toxins A and B

A

False

Only virulent strains have the toxins

85
Q

What does C. difficile do to tight junctions in the intestial epithelium?

A

C. diff infection disrupts the junctions between cells

86
Q

Definition

extreme or irrational fear of water, especially as a symptom of rabies in humans

A

Hydrophobia

87
Q

Describe the pathogenesis of Type D C. perfringens infections

A

Pro-ε-toxin: produced in intestine

=

Activated by trypsin/other proteases

=

Increases intestinal pemeability

=

Absorbed into systemic circulation

=

Endothelial cells of brain, kidney etc.

88
Q

Define

Histotoxic

A

poisonous to tissue.

89
Q

Define

C. perfringens

A

A bacterium that is the most common cause of gas gangrene, a lethal infection of soft tissue, especially muscle

90
Q

Define

Clostridium botulinum

A

a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum

91
Q

Why is Rabies almost impossible to completely eliminate?

A

There are so many wild-life reservoirs

92
Q

Define

Organoid

A

tiny, self-organized three-dimensional tissue cultures that are derived from stem cells

93
Q

What are the current C. difficile treatments?

A
  • Discontinuation of antibiotic and fluid replacement
  • More antibiotics!
    • Oral metronidazole and/or vancomycin
      • Relapses occur
      • Other antibiotics are also undergoing trials or have been approved, (eg fidaxomicin; narrow host range)
94
Q

What must Rabies virus bring to the cell in order to replicate?

A

RNA polymerase since it is (-) ssRNA

95
Q

Definition

The round shaped spores that C. tetani have

A

Round terminal (RT) spores

96
Q

What are the major virulence factors of C. difficile?

A

Toxins A and B

97
Q

What types of spores fo C. tetani produce?

A

Round terminal (RT) spores

98
Q

Define

Ezrin

A

family of proteins, which function as general cross-linkers between plasma membrane proteins and the actin cytoskeleton and are involved in the functional expression of membrane proteins at the cell surface

99
Q

Definition

Lyssavirus protein that acts as a cofactor of polymerase L, links L to N-RNA; required for transcription and replication; binds N, immune evasion

A

Phosphoprotein (P)

100
Q

True or False:

C. tetani spores need aerobic conditions to germinate

A

False

They need anaerobic conditions

101
Q

Which toxins are associated with C. perfringens type D infections?

A

α and ε toxins

102
Q

What happens to the Rabies virus in between entry and retrograde transport?

A

The virus is engulfed by the endosome which become acidic. The acidity causes a conformational change in the G protein causing the viral envelop and the endosomal membrane to fuse. This causes the nucleocapsid to be released into the cytoplasm

103
Q

Define

Large protein (L)

A

Lyssavirus protein required for replication and transcription; also known as RNA-dependent RNA polymerase

104
Q

Where do C. perfringens sporulate?

A

In the intestine

105
Q

Define

Retrograde

A

directed or moving backwards

106
Q

Define

Autocrine

A

denoting or relating to a cell-produced substance that has an effect on the cell by which it is secreted

107
Q

Definition

The ovoid shaped spores that most Clostridium spp., including C. perfringens and C. botulinum have

A

Ovoid subterminal (OST) spores

108
Q

What are the two forms of Rabies symptoms? Which one is more common?

A

Furious 80%

Paralytic 20%

109
Q

Define

Rabies

A

a contagious and fatal viral disease of dogs and other mammals, transmissible through the saliva to humans and causing madness and convulsions

110
Q

Define

IFN stimulated genes (ISGs)

A

a gene whose expression is stimulated by interferon

111
Q

How does Rabies P-protein block IFN induction and signalling?

A

Induction:

  • P-protein inhibits phosphorylation of IRF3, therefore IRF3 cannot be activated
  • Mechanism not clear

Signalling:

  • P-protein binds phosphorylated STAT1/2, prevents nuclear import
  • Blocks activation of ISGs likely using several ways
112
Q

Definition

the taxonomic home of numerous related viruses. Members of the order that are commonly known are, for instance, Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus

A

Mononegavirus infections

113
Q

True or False:

P-protein inhibition of STATs is critical to pathogenesis

A

True

114
Q

What is the virulence of C. perfringens assocaited with?

A

Production of a unique cocktails of 22 toxins

115
Q

Define

Australian Bat Lyssavirus (ABLV)

A

a virus that can be transmitted from bats to humans, causing serious illness

116
Q

Definition

atmosphere control units designed to be used when working with oxygen sensitive materials, product containment needs, and/or general isolation control

A

Anaerobic chamber

117
Q

Definition

Lyssavirus protein found on the outside or particle, immunogenic; required for viral entry into host cell

A

Glycoprotein (G)

118
Q

Define

α-toxin

A

a toxin produced by the bacterium Clostridium perfringens (C. perfringens) and is responsible for gas gangrene and myonecrosis in infected tissues

119
Q

Describe the oxygen requirements of C. difficile

A

Strict anaerobe

120
Q

Definition

an anaerobic bacterium of a large genus that includes many pathogenic species, e.g. those causing tetanus, gas gangrene, botulism, and other forms of food poisoning

A

Clostridium

121
Q

C. difficile only colonises the gut when?

A

The normal microbiota has been disrupted

122
Q

Definition

an instrument used in the production of an anaerobic environment. This method of anaerobiosis as others is used to culture bacteria which die or fail to grow in presence of oxygen (anaerobes)

A

Anaerobic jars

123
Q

Definition

directed or moving backwards

A

Retrograde

124
Q

List the steps to Rabies infection of the host

A
  1. Animal bite or scratch (virus in saliva)
  2. Infects muscle (replicates), transmitted to peripheral nerves, then central nervous system (CNS)
  3. Virus particles transport in along neuronal axons (i.e. retrograde = towards cell body) in vesicles using microtubules.
  4. When at neuronal cell body, released from vesicle, replicate, assemble new virus particles, then infect next neuron.
  5. Travels up spinal cord, leading to brain, causes encephalitis.
  6. Spreads to other organs (e.g. salivary glands)
125
Q

Define

Kozak sequence

A

a nucleic acid motif that functions as the translation initiation site in most mRNA (link) transcripts

126
Q

Definition

a bacterium that can cause symptoms ranging from diarrhea to life-threatening inflammation of the colon

A

Clostridium difficile

127
Q

Which Clostridia often causes ‘leaky gut’? Why?

A

C. difficile infection damages junctions between cells leading to ‘leaky gut’

128
Q

How do Rabies viruses leave the cell?

A

Budding

Gain membrane envelope from host cell

129
Q

What are the common clinical symptoms of Rabies?

A

Fever, mouth salivation, convulsions

Hydrophobia

Hallucinations

Hypersexual behaviour

Moments of clarity

Coma, death

130
Q

Definition

a host from which infectious agents are not transmitted to other susceptible hosts

A

Dead-end host

131
Q

Definition

a multifunctional protein that plays an important role in the transduction of Wnt signals and in the intercellular adhesion by linking the cytoplasmic domain of cadherin

A

β-catenin

132
Q

Definition

eosinophilic, sharply outlined, pathognomonic inclusion bodies (2–10 μm in diameter) found in the cytoplasm of certain nerve cells containing the virus of rabies, especially in pyramidal cells within Ammon’s horn of the hippocampus

A

Negri bodies

133
Q

After how long does the symptoms of Rabies appear?

A

20-90 days

134
Q

Definition

The inhibition of one bacterial organism by another

A

Bacterial antagonism

135
Q

How is a transciption gradient created for Rabies proteins?

A

Transcription gradient generated due to start-stop mechanism - polymerase complex doesn’t always re-engage with genome (N > P > M > G > L)

136
Q

Define

Bacterial antagonism

A

The inhibition of one bacterial organism by another

137
Q

Definition

poisonous to tissue.

A

Histotoxic

138
Q

Define

Round terminal (RT) spores

A

The round shaped spores that C. tetani have

139
Q

Order the Rabies proteins in terms of the quantity produced through transciption

A

N > P > M > G > L

140
Q

What does the integrity of the intestinal epithelium rely on?

A

Cellular polarity

Formation and maintenance of tight junctions

Renewal of the stem cell population and maintenance of the stem cell niche

141
Q

Does Australia have Rabies virus?

A

Not technically

It does have Australian Bat Lyssavirus Virus which is very similar to Rabies

142
Q

Define

Paracrine

A

relating to or denoting a hormone which has effect only in the vicinity of the gland secreting it

143
Q

Definition

the formation of nearly dormant forms of bacteria

A

Sporulation

144
Q

Define

Phosphoprotein (P)

A

Lyssavirus protein that acts as a cofactor of polymerase L, links L to N-RNA; required for transcription and replication; binds N, immune evasion

145
Q

What does C. difficile infection do to stem cells?

A

Alters their function

Can be seen in organoid growth

146
Q

Definition

inflammation of the brain, caused by infection or an allergic reaction

A

Encephalitis

147
Q

True or False:

The mRNA synthesised from the Rabies genome has a cap and poly-A-tail

A

True

Generated by L

148
Q

Where is β-toxin produced?

A

In the gut

149
Q

Which toxin is found in all C. perfringens?

A

α-toxin

150
Q

What are the functions of the rabies P protein?

A

Co-factor for RNA polymerase (L)

Links L and N-RNA

IFN antagonism

151
Q

Define

Matrix (M)

A

Lyssavirus protein required for viral assembly and budding

152
Q

Describe the pathogenesis of tetanus

A

Results in uncontrolled stimulation of muscles

  • Tension, cramping twisting of muscles
  • Spasms and convusions
  • Rigid paralysis
  • Death from spasms of the diaphragm and respiratory muscles
153
Q

Define

Nucleoprotein (N)

A

Lyssavirus protein that encapsidates the genome; required for transcription and replication

154
Q

Definition

a genus of RNA viruses in the family Rhabdoviridae, order Mononegavirales

A

Lyssavirus

155
Q

What two techniques are used to culture anaerobic bacteria?

A

Anaerobic Jars

Anaerobic Chambers

156
Q

Define

Enterotoxic

A

a toxin produced in or affecting the intestines, such as those causing food poisoning or cholera

157
Q

Definition

the bacteria responsible for the often fatal disease tetanus

A

Clostridium tetani

158
Q

Definition

a neurotoxic protein produced by the bacterium Clostridium botulinum and related species

A

botulinum neurotoxin (BoNT)

159
Q

Definition

a gene whose expression is stimulated by interferon

A

IFN stimulated genes (ISGs)

160
Q

Describe the pathogenesis of botulism

A

Results in an uncontrolled relaxation of muscles

  • Symptoms within 18 to 24 hours of ingesting toxin
  • Blurred vision, difficulty swallowing and speaking, muscle weakness, nausea, vomiting
  • Flaccid paralysis
  • Death due to cardiac or respiratory failure
161
Q

Definition

a term for a microbial imbalance or maladaptation on or inside the body, such as an impaired microbiota

A

Dysbiosis

162
Q

Define

Clostridium difficile

A

a bacterium that can cause symptoms ranging from diarrhea to life-threatening inflammation of the colon

163
Q

How does the normal microbiota provide non-specific immunity?

A
  1. Producing metabolic products that inhibit the growth of many pathogens
  2. Adhering to target host cells to prevent pathogens from colonising
  3. Depleting nutrients essential for the growth of pathogens
  4. Stimulating the immune system
164
Q

Define

E-cadherin

A

A transmembrane protein that links plasma membranes of adjacent cells together in a Ca2+-dependent manner; aids in maintaining the rigidity of the cell layer

165
Q

Describe the synthesis of the Rabies genome

A
166
Q

Define

Lyssavirus

A

a genus of RNA viruses in the family Rhabdoviridae, order Mononegavirales

167
Q

What happens during Type C C. perfringens infections when trypsin levels are low? What can cause low trypsin?

A

Low trypsin (sweet potatos contain trypsin inhibitors) means β-toxin remains active

=

Intestinal necrosis

=

Toxins to be absorbed

=

Damage to distant organs

168
Q

Describe the oxygen requirements of C. perfringens

A

Aerotolerant anaerobe

169
Q

Define

Exosporium

A

the outer surface layer of mature spores

170
Q

What can degrade β-toxin?

A

Gut trypsin

171
Q

What type of toxin is assocaited with C. perfringens?

A

Enterotoxin

172
Q

Where is pro-ε-toxin produced? What activates it?

A

Pro-ε-toxin is produced in the intestine and is activated by trypsin/other proteases

173
Q

What type of virus is Rabies caused by?

A

Lyssaviruses

BMS2052 (6 decks)

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