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
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
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
4
Q
Definition
Lyssavirus protein that encapsidates the genome; required for transcription and replication
A
Nucleoprotein (N)
5
Q
Definition
Lyssavirus protein required for viral assembly and budding
A
Matrix (M)
6
Q
These type of spores indicate what type of Clostridium?
A
C. tetani
7
Q
Define
Dysbiosis
A
a term for a microbial imbalance or maladaptation on or inside the body, such as an impaired microbiota
8
Q
A
9
Q
What does DNA dependent RNA polymerase do?
A
Transcribes DNA into RNA
aka RNA polymerase
10
Q
Definition
a toxin produced in or affecting the intestines, such as those causing food poisoning or cholera
A
Enterotoxic
11
Q
Which rabies proteins help form the Negri Bodies?
A
N and P
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
13
Q
Define
Glycoprotein (G)
A
Lyssavirus protein found on the outside or particle, immunogenic; required for viral entry into host cell
14
Q
Define
Ovoid subterminal (OST) spores
A
The ovoid shaped spores that most Clostridium spp., including C. perfringens and C. botulinum have
15
Q
What makes up the nucleocapsid of the Rabies virus?
A
The nucleocapsid is a Ribonucleoprotein (RNP) - complex composed of RNA and proteins
16
Q
Define
Adherens junctions (AJ)
A
a cell junction whose cytoplasmic face is linked to the actin cytoskeleton
17
Q
List the enterotoxic Clostridia
A
C. perfrigens
C. difficile
18
Q
Definition
tiny, self-organized three-dimensional tissue cultures that are derived from stem cells
A
Organoid
19
Q
What form is the Rabies virus genetic material in?
A
Negative sense RNA
(-)ssRNA
20
Q
How does Rabies virus travel from the bite site to the brain?
A
Retrograde axonal transport along the microtubules of neurons
21
Q
Which species of Clostridia cause tetanus?
A
C. tetani
22
Q
Which toxin is responsible for intestinal necrosis seen in C. perfringens?
A
β-toxin
23
Q
What are the three broad strategies that viruses have to avoid IFN action?
A
- General inhibition of host gene expression
- Sequestration/masking of PAMPs
- Sequestration/modification of signally components
24
Q
Define
RNA antigenome
A
The complementary strand of RNA from which the genome of a virus is constructed
25
Which Rabies genes are required for RNA synthesis?
N, P and L
26
List the neurotoxic Clostridia
C. tetani
C. botulinum
27
What are the basic characteristics of Clostridium?
Gram-positive rods
Obligate anaerobes
Form heat resistant endospores
28
# Define
Dead-end host
a host from which infectious agents are not transmitted to other susceptible hosts
29
# Define
Hydrophobia
extreme or irrational fear of water, especially as a symptom of rabies in humans
30
When is the tetanus toxin released?
Released when the bacteria die
31
How does Rabies virus enter cells?
Rabies virus enters by receptor-mediated endocytosis
32
What are the new C. difficile treatments under consideration?
* 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
33
# Definition
a virus that can be transmitted from bats to humans, causing serious illness
Australian Bat Lyssavirus (ABLV)
34
What do you need to make a modified Rabies virus?
Rabies genome
N-protein
P-protein
L-protein
35
Describe the structure of the Rabies P-protein
36
# Define
Clostridium
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
37
This posture is typical of which type of C. perfringens infection?
Type D
38
Which of the species of Clostridia cause botulism?
C. botulinum
39
# 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
E-cadherin
40
What are Negri Bodies?
Membrane-less cytoplasmic inclusions caused by Rabies infection
41
# Definition
The complementary strand of RNA from which the genome of a virus is constructed
RNA antigenome
42
# Definition
a contagious and fatal viral disease of dogs and other mammals, transmissible through the saliva to humans and causing madness and convulsions
Rabies
43
# Definition
a nucleic acid motif that functions as the translation initiation site in most mRNA (link) transcripts
Kozak sequence
44
# Definition
a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum
Clostridium botulinum
45
# Definition
Lyssavirus protein required for replication and transcription; also known as RNA-dependent RNA polymerase
Large protein (L)
46
What is the order of Rabies virus genes?
N, P, M, G then L
47
# Define
Clostridium tetani
the bacteria responsible for the often fatal disease tetanus
48
Which toxin is responsible for the histotoxic effects of C. perfringens?
α-toxin
49
# Define
Encephalitis
inflammation of the brain, caused by infection or an allergic reaction
50
True or False:
Rabies viruses only use one method to disrupt the IFN pathway
False
Viruses use many ways to disrupt IFN pathway
51
What are the three main types of IFN?
**Type I:** IFNα and IFNβ - direct response to infection broad cellular expression and receptors
**Type II:** IFNγ - immune cells
**Type III:** IFNλ
52
# Define
Negri bodies
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
53
What makes up the three main components of the assembled Rabies virus?
1. Nucleocaspid (RNA, N, P, L)
2. M (at plasma membrane)
3. G (glycosylated - sugar groups added)
54
What shape are Rabies viruses?
Helical
55
List the 4 different ways that the rabies P-protein inhibits IFN signalling
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
56
# Definition
a toxin produced by the bacterium Clostridium perfringens (C. perfringens) and is responsible for gas gangrene and myonecrosis in infected tissues
α-toxin
57
What type of spores do most Clostridium spp. including C. sporogenes and C. botulinum produce?
Ovoid subterminal (OST) spores
58
# Define
Mononegavirus infections
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
59
What toxins do Type C C. perfrigens infections involve?
α and β toxins
60
# Define
Sporulation
the formation of nearly dormant forms of bacteria
61
How many genes do Lyssaviruses encode? What are they?
5
N, P, M, G, L
62
What is the new name for the Clostrdium species?
Clostridioides
63
What does the α-toxin of Clostridia do?
Phospholipase
Disrupts host-cell plasma membranes
Extensive destruction of cells and tissues
64
# Define
Anaerobic jars
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)
65
What happens to epithelial cell polarity in C. difficile infection?
Completely disrupted
66
True or False
Both botulism and tetanus can be prevented with a vaccine
False
Tetanus has a toxoid vaccine available but botulism has no vaccine available (antitoxin can be used)
67
Which Rabies protein binds to N-RNA and L (linking them together)?
P protein
68
# Definition
relating to or denoting a hormone which has effect only in the vicinity of the gland secreting it
Paracrine
69
What causes sporulation?
Adverse conditions
70
# Define
Anaerobic chamber
atmosphere control units designed to be used when working with oxygen sensitive materials, product containment needs, and/or general isolation control
71
The Rabies genome (-RNA) makes _________ (+RNA) in order to make new genomes
The Rabies genome (-RNA) makes **antigenome** (+RNA) in order to make new genomes
72
# Define
botulinum neurotoxin (BoNT)
a neurotoxic protein produced by the bacterium Clostridium botulinum and related species
73
List the histotoxic Clostridia
C. perfrigens
C. septicum
C. sordellii
74
Where does replicaiton of the Rabies viral genome occur?
In "liquid" Negri Bodies
75
What are the three groups of pathogenic clostridia?
Neurotoxin
Enterotoxix
Histotoxic
76
Oxygen causes Clostridium to do what?
Form endospores
77
# Definition
a cell junction whose cytoplasmic face is linked to the actin cytoskeleton
Adherens junctions (AJ)
78
What conditions often develop following microbiota dysbiosis?
Candida
C. difficile infection
79
Which type of Clostridia causes gas gangrene?
C. perfringens
80
What function do many IFN stimulated genes (ISGs) have?
Antiviral properties
81
Are Rabies viruses enveloped or naked?
Enveloped
82
True or False
All strains of C. difficile have toxins A and B
False
Only virulent strains have the toxins
83
What does C. difficile do to tight junctions in the intestial epithelium?
C. diff infection disrupts the junctions between cells
84
# Definition
extreme or irrational fear of water, especially as a symptom of rabies in humans
Hydrophobia
85
Describe the pathogenesis of Type D C. perfringens infections
Pro-ε-toxin: produced in intestine
=
Activated by trypsin/other proteases
=
Increases intestinal pemeability
=
Absorbed into systemic circulation
=
Endothelial cells of brain, kidney etc.
86
# Define
Histotoxic
poisonous to tissue.
87
# Define
C. perfringens
A bacterium that is the most common cause of gas gangrene, a lethal infection of soft tissue, especially muscle
88
# Define
Clostridium botulinum
a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum
89
Why is Rabies almost impossible to completely eliminate?
There are so many wild-life reservoirs
90
# Define
Organoid
tiny, self-organized three-dimensional tissue cultures that are derived from stem cells
91
What are the current C. difficile treatments?
* 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)
92
What must Rabies virus bring to the cell in order to replicate?
RNA polymerase since it is (-) ssRNA
93
# Definition
The round shaped spores that C. tetani have
Round terminal (RT) spores
94
What are the major virulence factors of C. difficile?
Toxins A and B
95
What types of spores fo C. tetani produce?
Round terminal (RT) spores
96
# Define
Ezrin
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
97
# 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
Phosphoprotein (P)
98
True or False:
C. tetani spores need aerobic conditions to germinate
False
They need **anaerobic** conditions
99
Which toxins are associated with C. perfringens type D infections?
α and ε toxins
100
What happens to the Rabies virus in between entry and retrograde transport?
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
101
# Define
Large protein (L)
Lyssavirus protein required for replication and transcription; also known as RNA-dependent RNA polymerase
102
Where do C. perfringens sporulate?
In the intestine
103
# Define
Retrograde
directed or moving backwards
104
# Define
Autocrine
denoting or relating to a cell-produced substance that has an effect on the cell by which it is secreted
105
# Definition
The ovoid shaped spores that most Clostridium spp., including C. perfringens and C. botulinum have
Ovoid subterminal (OST) spores
106
What are the two forms of Rabies symptoms? Which one is more common?
Furious 80%
Paralytic 20%
107
# Define
Rabies
a contagious and fatal viral disease of dogs and other mammals, transmissible through the saliva to humans and causing madness and convulsions
108
# Define
IFN stimulated genes (ISGs)
a gene whose expression is stimulated by interferon
109
How does Rabies P-protein block IFN _induction_ and _signalling_?
**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
110
# 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
Mononegavirus infections
111
True or False:
P-protein inhibition of STATs is critical to pathogenesis
True
112
What is the virulence of C. perfringens assocaited with?
Production of a unique cocktails of 22 toxins
113
# Define
Australian Bat Lyssavirus (ABLV)
a virus that can be transmitted from bats to humans, causing serious illness
114
# Definition
atmosphere control units designed to be used when working with oxygen sensitive materials, product containment needs, and/or general isolation control
Anaerobic chamber
115
# Definition
Lyssavirus protein found on the outside or particle, immunogenic; required for viral entry into host cell
Glycoprotein (G)
116
# Define
α-toxin
a toxin produced by the bacterium Clostridium perfringens (C. perfringens) and is responsible for gas gangrene and myonecrosis in infected tissues
117
Describe the oxygen requirements of C. difficile
Strict anaerobe
118
# 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
Clostridium
119
C. difficile only colonises the gut when?
The normal microbiota has been disrupted
120
# 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)
Anaerobic jars
121
# Definition
directed or moving backwards
Retrograde
122
List the steps to Rabies infection of the host
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)
123
# Define
Kozak sequence
a nucleic acid motif that functions as the translation initiation site in most mRNA (link) transcripts
124
# Definition
a bacterium that can cause symptoms ranging from diarrhea to life-threatening inflammation of the colon
Clostridium difficile
125
Which Clostridia often causes 'leaky gut'? Why?
C. difficile infection damages junctions between cells leading to 'leaky gut'
126
How do Rabies viruses leave the cell?
Budding
Gain membrane envelope from host cell
127
What are the common clinical symptoms of Rabies?
Fever, mouth salivation, convulsions
Hydrophobia
Hallucinations
Hypersexual behaviour
Moments of clarity
Coma, death
128
# Definition
a host from which infectious agents are not transmitted to other susceptible hosts
Dead-end host
129
# 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
Negri bodies
130
After how long does the symptoms of Rabies appear?
20-90 days
131
# Definition
The inhibition of one bacterial organism by another
Bacterial antagonism
132
How is a transciption gradient created for Rabies proteins?
Transcription gradient generated due to start-stop mechanism - polymerase complex doesn't always re-engage with genome (**N** \> **P** \> **M** \> **G** \> **L**)
133
# Define
Bacterial antagonism
The inhibition of one bacterial organism by another
134
# Definition
poisonous to tissue.
Histotoxic
135
# Define
Round terminal (RT) spores
The round shaped spores that C. tetani have
136
Order the Rabies proteins in terms of the quantity produced through transciption
**N \> P \> M \> G \> L**
137
What does the integrity of the intestinal epithelium rely on?
Cellular polarity
Formation and maintenance of tight junctions
Renewal of the stem cell population and maintenance of the stem cell niche
138
Does Australia have Rabies virus?
Not technically
It does have Australian Bat Lyssavirus Virus which is very similar to Rabies
139
# Define
Paracrine
relating to or denoting a hormone which has effect only in the vicinity of the gland secreting it
140
# Definition
the formation of nearly dormant forms of bacteria
Sporulation
141
# Define
Phosphoprotein (P)
Lyssavirus protein that acts as a cofactor of polymerase L, links L to N-RNA; required for transcription and replication; binds N, immune evasion
142
What does C. difficile infection do to stem cells?
Alters their function
Can be seen in organoid growth
143
# Definition
inflammation of the brain, caused by infection or an allergic reaction
Encephalitis
144
True or False:
The mRNA synthesised from the Rabies genome has a cap and poly-A-tail
True
Generated by L
145
Where is β-toxin produced?
In the gut
146
Which toxin is found in all C. perfringens?
α-toxin
147
What are the functions of the rabies P protein?
Co-factor for RNA polymerase (L)
Links L and N-RNA
_IFN antagonism_
148
# Define
Matrix (M)
Lyssavirus protein required for viral assembly and budding
149
Describe the pathogenesis of tetanus
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
150
# Define
Nucleoprotein (N)
Lyssavirus protein that encapsidates the genome; required for transcription and replication
151
# Definition
a genus of RNA viruses in the family Rhabdoviridae, order Mononegavirales
Lyssavirus
152
What two techniques are used to culture anaerobic bacteria?
Anaerobic Jars
Anaerobic Chambers
153
# Define
Enterotoxic
a toxin produced in or affecting the intestines, such as those causing food poisoning or cholera
154
# Definition
the bacteria responsible for the often fatal disease tetanus
Clostridium tetani
155
# Definition
a neurotoxic protein produced by the bacterium Clostridium botulinum and related species
botulinum neurotoxin (BoNT)
156
# Definition
a gene whose expression is stimulated by interferon
IFN stimulated genes (ISGs)
157
Describe the pathogenesis of botulism
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
158
# Definition
a term for a microbial imbalance or maladaptation on or inside the body, such as an impaired microbiota
Dysbiosis
159
# Define
Clostridium difficile
a bacterium that can cause symptoms ranging from diarrhea to life-threatening inflammation of the colon
160
How does the normal microbiota provide non-specific immunity?
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**
161
# Define
E-cadherin
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
162
Describe the synthesis of the Rabies genome
163
# Define
Lyssavirus
a genus of RNA viruses in the family Rhabdoviridae, order Mononegavirales
164
What happens during Type C C. perfringens infections when trypsin levels are low? What can cause low trypsin?
Low trypsin (sweet potatos contain trypsin inhibitors) means β-toxin remains active
=
Intestinal necrosis
=
Toxins to be absorbed
=
Damage to distant organs
165
Describe the oxygen requirements of C. perfringens
Aerotolerant anaerobe
166
# Define
Exosporium
the outer surface layer of mature spores
167
What can degrade β-toxin?
Gut trypsin
168
What type of toxin is assocaited with C. perfringens?
Enterotoxin
169
Where is pro-ε-toxin produced? What activates it?
Pro-ε-toxin is produced in the intestine and is activated by trypsin/other proteases
170
What type of virus is Rabies caused by?
Lyssaviruses
