Module 12 - Bacterial Pathogenesis Flashcards
1
Q
In what two groups can bacteria be divided into?
A
Pathogenic and nonpathogenic
2
Q
What is pathogenesis?
A
Processes used by pathogens to produce disease
3
Q
What are the key aspects of bacterial pathogenesis?
A
Attachment to host tissue to gain access, avoid host defense, damage host tissues to get nutrients and replicate
4
Q
What is a principle feature in pathogen evolution?
A
Genetic mobility
5
Q
What are virulence factors?
A
Pathogen products that enhance the ability to cause disease
6
Q
In what common ways do virulence factors act?
A
They can gain access to tissue, overcome host defense, and get nutrients (by damaging cells or stealing from the host)
7
Q
What diseases does Neisseria gonorrhoeae lead to?
A
STIs such as gonorrhea
8
Q
What virulence factors are produced by Neisseria gonorrhoeae?
A
Fimbriae, IgA protease, and LOS
9
Q
What does Neisseria gonorrhoeae do with its fimbriae?
A
Attaches to host cell and invades underlying tissues
10
Q
What does Neisseria gonorrhoeae do with LOS?
A
It invokes an intense inflammatory response in the host
11
Q
Why would a pathogenic bacteria want to induce inflammation?
A
It damages host tissue, which facilitates invasion and provides nutrients
12
Q
How come pathogenic bacteria want to stop the host immune system?
A
The host defense system can stop entry and growth of pathogenic bacteria
13
Q
What does Neisseria gonorrhoeae do with IgA protease?
A
It uses it to avoid the host defense system
14
Q
How can pathogenic bacteria avoid the host defense system?
A
By changing surface antigens, or by producing IgA protease
15
Q
What disease does Bordetella pertussis lead to?
A
Whooping cough
16
Q
What disease does Escherichia coli O157:H7 lead to?
A
Hemorrhagic colitis and kidney failure
17
Q
What disease does Helicobacter pylori lead to?
A
Gastritis, ulcers
18
Q
What disease does Streptococcus pneumoniae lead to?
A
Pneumonia, meningitis
19
Q
What disease does Streptococcus pyogenes lead to?
A
Various skin, throat, and systemic infections
20
Q
What do the symptoms of Neisseria gonorrhoeae depend on?
A
The site of infection
21
Q
What do nonpathogenic bacteria do (when growing)?
A
They colonizes and do not directly attach to host cell
22
Q
What are some common attachment factors used by pathogenic bacteria?
A
Fibronectin binding proteins, fimbriae, outer membrane molecules, and other specialized proteins for attachment
23
Q
What are adhesions?
A
Molecules that allow bacteria to bind to host tissues
24
Q
In which bacteria are fibronectin binding proteins best studied in?
A
Streptococcus pyogenes, Staphylococcus aureus, and E. coli
25
What is fibronectin?
A plasma glycoprotein in plasma and as fibers in extracellular matrix
26
How come fibronectin is a prime target for pathogen binding?
It is present everywhere
27
What disease does Corynebacterium diphtheria lead to?
Diptheria
28
What disease does Clostridium difficile lead to?
Colitis
29
What disease does Clostridium perfringens lead to?
Gas gangrene
30
What disease does Mycobacterium tuberculosis lead to?
Tuberculosis
31
What disease does Staphylococcus aureus lead to?
Various skin and invasive diseases
32
What disease does Streptococcus pyogenes lead to?
Various invasive and toxic diseases
33
What disease does Treponema pallidum lead to?
Syphilis
34
What disease does Borrelia burgdorferi lead to?
Lyme disease
35
What disease does Porphyromonas gingivalis lead to?
Gum disease
36
What do fimbriae do?
They are used for attachment to host tissues and nonbiological surfaces (medical implants)
37
What is a fimbriae?
A specialized pili with an adhesive tip?
38
How come fimbriae are used to aid in adhesion?
It can help span the distance of repulsion
39
What repulsion is there when bacteria try to bind to host tissues?
Cell surfaces have net negative charge that causes electrostatic repulsion
40
What is found at the end of a fimbriae strand?
A specific adhesive tip composed of a tip protein
41
What does the adhesive tip of a fimbriae do?
It is used for attachment by targeting oligosaccharides
42
True or false: several different types of fimbriae can be produced by a single bacterium
True: they are frequently modified
43
Why are fimbriae modified?
To respond to environmental conditions
44
How does Neisseria gonorrhaea use its fimbriae?
It is needed for attachment to epithelial cells of urethra and cervix
45
What happens once infection has been established (in terms of fimbriae)?
Fimbriae expression can be turned on or off
46
How can fimbriae avoid host immune system?
By undergoing an amino acid change through genetic combination
47
What is the consequence of fimbriae undergoing amino acid change?
By the time one specific antibody is made, another fimbriae is produced
48
How do E. coli cells form lesions to obtain nurtients?
Through interactions of intimate virulence factors
49
What special adherence proteins are used by E. coli?
Intimin and Tir
50
Where is Tir found?
It is produced by E. coli, and translocated to intestinal cells
51
Where is Intimin found?
It is produced by E. coli
52
When do intestinal cells express Tir?
When E. coli insert it through a type III secretion pathway
53
What happens once Tir is inserted into intestinal cells?
It can interact with Intimin found on the E. coli cell
54
What happens when Tir interacts with Intimim?
A pedestal is formed for the E. coli cell
55
What is a capsule?
A well organized polysaccharide layer that surrounds some bacterial cells
56
What is another name for a capsule?
The glycocalyx
57
What are capsules composed of?
Usually polysaccharides, but sometimes polypeptides
58
True or false: capsules can help adhere to surfaces
True: they can bind to receptors to help adhere to surfaces
59
What is the primary role of capsules for pathogens?
To protect the bacterium from early immune defenses (phagocytosis and lyse from complement)
60
What happens to nonencapsulated bacteria (in terms of early immune defenses)?
They are opsonized and are regularly phagocytosed by phagocytes
61
What happens to encapsulated bacteria (in terms of early immune defenses)?
The antibody must move through the capsule to attach to the cell surface, so it will not be available for phagocyte binding
62
What is needed for phagocytosis of encapsulated bacteria to occur?
An antibody specific to the capsule
63
What is the result of constructing a capsule from host self molecules?
It prevents stimulation of the host immune response
64
What is the purpose of capsules containing water?
It protects the bacteria against desiccation
65
What do capsules exclude?
Bacterial viruses
66
True or false: immunity to one type of capsule is sufficient
False: immunity to one capsule type does not result in immunity to other types
67
What is the capsule of Bacillus anthracis made out of?
Poly-D-glutamic acid
68
What is the capsule of Streptococcus pyogenes made out of?
Hyaluronic acid
69
What is the capsule of Haemophilus influenzae made out of?
There are six different capsule types
70
What is the capsule of Neisseria meningitidis made out of?
Sialic acid
71
What is the capsule of Pseudomonas aeruginosa made out of?
Alginate (biofilm formation)
72
How do bacteria release toxins or virulence factors?
Either through their lysis, secretion to extracellular environment, or injection directly into a host cell
73
What are major virulence factors in gram negative bacteria?
Type III and Type IV secretion systems
74
What are some examples of gram negative bacteria that use Type III secretion systems?
E. coli, Shigella sonnei, Klebsiella pneumoniae, Nesseria gonorrhoeae, Salmonella Typhimurium
75
What are Type III secretion systems?
Injection assemblies that deliver virulence factors directly into the target cell
76
How do Type III secretion systems work?
They form a channel that passes through plasma membrane and outer membrane of pathogen and host cell membrane
77
Which is more common: Type III or Type IV secretion systems?
Type III secretion systems
78
How do Type IV secretion systems work?
They deliver molecules across the plasma membrane to inject virulence factors
79
What are Type III and IV secretion systems often encoded with?
The gene products that they will inject
80
Why is iron a limiting nutrient for the pathogen?
It is kept tightly bound by host iron binding proteins
81
What are the 4 strategies pathogens can use to obtain iron from the host?
Siderophores, transport proteins, low pH, and hemolysin
82
What are siderophores?
Bacterial iron binding proteins
83
How do siderophores obtain iron?
They compete with host iron binding proteins for iron
84
How are transport proteins used to obtain iron?
They can transport host iron binding proteins into the bacterial cell
85
How can low pH be used to obtain iron?
It reduces the ability of host iron binding proteins to bind to iron
86
What do hemolysins do?
Lyse red blood cells
87
How can hemolysins be used to obtain iron?
They can lyse red blood cells to release intracellular iron and other nutrients
88
Why do bacteria use toxins?
To gain nutrients from the host
89
What is a toxin?
A poisonous substance produced by an organism
90
What are the two categories of toxins?
Endotoxins and exotoxins
91
What are endotoxins, and what do they do?
They are part of the cell wall structure, and induce inflammatory responses
92
What are some examples of endotoxins?
LPS and LTA
93
What type of bacteria use LPS?
Gram-negative bacteria
94
What type of bacteria use LTA?
Gram-positive bacteria
95
What does LPS stand for?
Lipopolysaccharide
96
What does LTA stand for?
Lipoteichoic acid
97
What are exotoxins?
Soluble proteins released outside of the producing cell, or passively released upon bacterial lysis
98
What are some examples of exotoxins?
AB toxins, cytolysins, and super antigens
99
What are AB toxins?
Exotoxins with two subunits (A and B)
100
What does the A subunit do in an AB toxin?
It has toxic enzymatic activity
101
What does the B subunit do in an AB toxin?
It binds to the host cell receptor
102
Generally, what is a cytotoxin?
A substance toxic to cells
103
What are cytolysins?
Bacterial cytotoxins that act on the plasma membrane
104
What are super antigens and what do they do?
Exotoxins that can non specifically stimulate T cells to secrete cytokines
105
What does LOS stand for?
Lipooligosaccharide
106
What is the structure of LOS?
Lipid A and a core polysaccharide
107
What is the structure of LPS?
Lipid A, a core polysaccharide, and an O antigen
108
How was LPS discovered?
Scientists isolated a heat stable element from gram negative bacteria that was responsible for many toxic effects of systemic diseases
109
Where is LPS found?
In the outer membrane of gram-negative bacteria
110
What is the most common type of endotoxin?
LPS
111
What is the composition of the O antigen?
Repeating units of polysaccharide
112
What does the O antigen do?
It is strain specific, and the target of the immune response
113
What is used for serotyping?
The O antigen
114
What is the composition of the core polysaccharide?
Various sugars with side chains that are genus or species specific
115
What is the innermost component of LPS?
Lipid A
116
What does Lipid A do?
It anchors LPS to outer membrane, and causes inflammation
117
What is the composition of Lipid A?
Unusual fatty acids
118
What is the toxic portion of LPS?
Lipid A
119
What does Neisseria meningitis cause?
Inflammation of meninges
120
What are meninges?
Lining that surrounds the brain and spinal cord
121
What was shown to be responsible for the toxic properties of Neisseria meningitis?
Lipid A
122
What does endotoxin do in low concentration?
It stimulates immune system response that can prevent disease
123
True or false: systemic production of endotoxin is deadly
True: this can overwork the immune system
124
Where is LTA found?
Anchored to the plasma membrane in most gram positive pathogens
125
What is LTA?
A cell wall molecule
126
True or false: LTA is recognized by TLRs?
True: like LPA, LTA is recognized by TLRs
127
What does LTA do?
It induces inflammation
128
True or false: LTA is useful in small quantities
True: the endotoxin produces septic shock only when there are large amounts of bacteria present
129
What is the protective activity of a fever?
Inhibition of pathogen replication, increase in immune cell activities
130
What is the protective activity of complement activation?
Lysis by MAC formation, induction of inflammation
131
What is the protective activity of inflammation?
Transport of immune cells and molecules to site of infection
132
What is the protective activity of B-cell proliferation?
Antibody production
133
What is the protective activity of IFN-gamma expression from T cells
Activation of macrophages and NK cells
134
What is the protective activity of stimulation of the clotting cascade?
Prevention of pathogen spread
135
How are exotoxins grouped?
By structure (AB toxins), molecular activity (super antigens), or cellular activity (cytotoxins)
136
Which bacteria have an AB toxin with one B subunit?
Diptheria, tetanus, and botulinum
137
Which bacteria have an AB toxin with multiple of the same B subunit?
Cholera and Shiga
138
Which bacteria have an AB toxin with multiple different B subunits?
Pertussis
139
How does Corynebacterium diphtheria AB toxin spread?
It is absorbed in the circulatory system, where it is distributed to other organs (heart, kidney, liver, and spleen)
140
What does Corynebacterium diphtheria AB toxin do?
It prevents protein synthesis
141
How does Corynebacterium diphtheria AB toxin enter the host cell?
Through receptor mediated endocytosis
142
What happens when the AB toxin is in the endosome?
Acidification causes a conformational change, forming a channel
143
What happens once the B subunit forms a channel in the endosome?
The A subunit can inactivate EF2 to stop protein synthesis
144
What does EF2 do?
It is a translation factor needed for protein synthesis
145
What does EF2 stand for?
Elongation factor 2
146
Which bacteria produces Shiga toxin?
E. coli O157:H7
147
How come cattle, pigs, sheep, and deer can be a reservoir of infection for Shiga toxin?
These animals do not have the Shiga receptors, but these receptors are enriched in human kidney cells
148
What do Shiga toxins do?
They cleave ribosomal RNA to prevent protein synthesis
149
How does Diphtheria toxin inactivate EF2?
By adding an ADP ribose to EF2
150
What is ADP-ribosylation?
The process of adding an ADP ribose to a protein
151
How does EF2 work?
It is needed for movement of ribosomes along mRNA in eukaryotes
152
How does Pertussis toxin work?
It adds an ADP ribose to Gi to activate adenylyl cyclase
153
How does Cholera toxin work?
It adds an ADP ribose to Gs to activate adenylyl cyclase
154
What is the effect of increased activation of adenylyl cyclase?
Disruption of ion and water balance
155
What are two examples of AB toxins that cleave host proteins?
Botulinum toxin and tetanus toxin
156
What do botulinum toxin and tetanus toxin have in common?
They are both neural toxins, similar in structure and function, and act on SNARE proteins
157
What does SNARE protein stand for?
Snap receptor
158
What do SNARE proteins do?
They are required to release neurotransmitters
159
What are SNARE proteins?
A large protein super family, consisting of more than 60 members in yeast and mammalian cells
160
What happens when neurotoxins cleave SNARE proteins?
They prevent neurotransmitter release
161
What does acetylcholine do?
Causes muscle contraction
162
What does botulinum toxin lead to?
Flaccid paralysis (botulism)
163
What is flaccid paralysis?
Weakness of muscle and loss of muscle tone (limp and cannot contract)
164
How does botulinum toxin lead to flaccid paralysis?
It prevents release of acetylcholine
165
How can flaccid paralysis be fatal?
If it affects respiratory muscles (suffocation)
166
What is one possible cause of sudden infant death syndrome?
Infant botulism
167
What does tetanus toxin lead to?
Spastic paralysis (tetanus)
168
What is spastic paralysis?
Unusual tightness or stiffness of muscles (persistent contraction)
169
How does tetanus toxin lead to spastic paralysis?
It prevents release of glycine and GABA, which leads to continuous secretion of acetylcholine
170
What does GABA stand for?
Gamma aminobutyric acid
171
How do patients usually die in botulism or tetanus?
Respiratory failure
172
What is needed to release neurotransmitters in vesicles?
The vesicles must fuse with the neuronal plasma membrane
173
Which SNARE proteins help with membrane fusion?
Synaptobrevin, SNAP-25, and syntaxin
174
Where is synaptobrevin found?
Inserted in the vesicle membrane
175
Where is syntaxin found?
Inserted in the neuronal membrane
176
What does SNAP-25 do?
It binds to synaptobrevin and syntaxin to form a complex that allows the membranes to fuse
177
What is the primary role of SNARE proteins?
To mediate fusion of vesicle with target membrane bound compartments
178
What is needed for normal muscular contraction?
Release of acetylcholine neurotransmitter from vesicles in the terminals of motor neurons
179
What does botulinum toxin type A do?
It cleaves SNAP-25 to prevent muscular contraction
180
How toxic is botulinum toxin?
300,000x more toxic than snake venom
181
What is one of the most important toxins discovered?
Botulinum toxin
182
What toxins attack synaptobrevin?
Tetanus toxin, botulinum toxin type B, D, F, G
183
What toxins attack SNAP-25?
Botulinum toxin type A, C, E
184
What toxins attack syntaxin?
Botulinum toxin type C
185
How is muscular contraction halted?
By the release of neuroinhibitory neurotransmitters glycine and GABA
186
How does tetanus toxin move through the body?
It is taken up by motor neurons, transported to the central nervous system, and then to the inhibitory neurons
187
What does tetanus toxin do?
It cleaves synaptobrevin in inhibitory neurons
188
How do glycine and GABA work?
They act on motor neurons to block acetylcholine release, ending contraction
189
How does tetanus toxin lead to continuous muscle contraction?
It allows acetylcholine to be continually released from stimulated neurons
190
True or false: cytolysins can destruct membranes without creating lysis
True: they do not have to cause lysis
191
What does MDT stand for?
Membrane damaging toxin
192
How much of bacterial protein toxins are cytolysins?
1/3
193
How many cytolysins have been studied and published?
70
194
How are cytolysins named?
According to the cells that they can destroy
195
What do hemolysins do?
Lyse red blood cells
196
What is the result of hemolysis?
A zone of clearing surrounding the bacteria
197
What are hemolysis patterns used for?
Identifying streptococcus species (characteristic patterns)
198
What are the three different types of hemolysis?
Alpha, beta, and gamma
199
What is alpha hemolysis?
Partial hemolysis
200
What is beta hemolysis?
Complete hemolysis
201
What is gamma hemolysis?
No hemolysis
202
What type of hemolysis do streppygenes bacteria that cause strep throat cause?
Beta hemolysis
203
What type of hemolysis do strep pneumonia bacteria cause?
Alpha hemolysis
204
What type of hemolysis do Entercoccus faecalis cause?
Gamma hemolysis
205
What causes the green color in alpha hemolysis?
Partially decomposed hemoglobin
206
What categories can cytolysins be grouped into?
Pore-forming toxins and membrane degrading toxins
207
How do pore forming cytolysins work?
They are produced as monomers that polymerize in the membrane to form a circular pore
208
What is an example of a pore forming cytolysin?
Alpha toxin from Staphylococcus aureus, and perfringolysin from Clostridium perfringens
209
What do pore forming cytolysins do at high concentrations?
They form many holes, causing cell lysis
210
What do pore forming cytolysins do at low concentrations?
They allow influx of calcium ions, which causes membrane damage and induces apoptosis
211
How does perfringolysin work?
It binds to membrane cholesterol and contributes to tissue destruction in gas gangrene
212
What are the characteristics of gas gangrene?
Muscle necrosis and intense gas productions
