Bacterial Pathogenesis - Sumby Flashcards
1
Q
How common is death by infectious disease or parasites worldwide?
A
2nd most common
2
Q
Bacteria outnumber human cells how many fold?
A
3 fold
3
Q
What are the stats in number, wt, vol, and gene:gene: ratio for bacteria vs human?
A
100 trillion bacterial cells
3 pounds in weight
3 pints in volume
50:1 genes
4
Q
Mutualistic and commensual relationships predominate over (blank)
A
parasitic
5
Q
What types of microorganisms make up the human microbiome?
A
bacteria, fungi, viruses, and protozoa
6
Q
What are the four benefits we get from having a microbiome?
A
- easier nutrient digestion
- educates innate defenses and stims both innate and adaptive immunity
- maintains epithelial boundary functions and integrity
- colonization resistance against pathogens
7
Q
what are some negative disease states caused by our microbiome?
A
psoriasis, obesity, IBS, colorectal carcinoma
8
Q
How many CHO digesting enzymes does the human genome code for? How many does a gut flora have?
A
20; 260
9
Q
The fact that Japanese people have an enzyme from bacteria that allows them to digest seaweed is evidence that the micrbiome promotes (blank)
A
adaptation
10
Q
What is first line therapy for C diff?
A
two week oral vancomycin
11
Q
Why are relapsing infections common in C dff? Why is this a problem?
A
spores are antibiotic resistant; multiple rounds damages gut microbiome
12
Q
What is the success rate of a fecal transplantation for curing C. diff? How is it placed?
A
95%; in GI tract during colonoscopy, DIY enema, or via nasal tube
13
Q
T/F: The diversity and abundance of different bacterial species vary from person to person.
A
True, exposure to different microbes
or environments alters the microbiome.
14
Q
T/F: . The diversity and abundance of different bacterial species vary over time in a single person.
A
True, microbiome is constantly changing over time.
15
Q
T/F: H. pylori dramatically alters the diversity of the stomach microbiome.
A
True, H. pylori infection decreases the number and abundance of other bacterial species.
16
Q
T/F: Variation in the gut microbiome can affect susceptibility to C. difficile infection.
A
True, the microbiome has a major role in protecting against C. difficile and many other infections.
17
Q
T/F: Three-year-old identical twins have identical skin microbiomes.
A
False, no two individuals microbiomes are identical.
18
Q
What is the time between the moment the person is exposed to the microbe (or toxin) and the appearance of symptoms (note info is an important diagnostic clue?
A
Incubation period
19
Q
what is the time during which nonspecific symptoms occur?
A
prodrome period
20
Q
What is the time during which specific clinical signs and symptoms occur?
A
Disease period
21
Q
What is the : time during which symptoms resolve and health is restored?
A
recovery period
22
Q
After the recovery period, some people become (blank) carriers of the organism and in others (blank) infections develop.
A
chronic, latent
23
Q
Some people have subclinical infections during which they remain asymptomatic; the presence of (blanks) reveals that a prior infection has occurred.
A
Abs
24
Q
What is convalescence?
A
period after the decline of the infection in which there are no signs or symptoms
25
What are the two modes of human-human transmission?
Direct contact or vector
26
What are the two modes of transmission from animal-to-human?
direct contact or vector
27
Human diseases in which animals are the resevoir are called (blank) and the pathogens are called zoonotic
zoonoses
28
What are the main PORTALS OF ENTRY?
respiratory, GI, GU tracts, and skin
29
T/F: any object can be capable of carrying an infectious organism. This is called a fomite.
True
30
What are the four routes of human-human transmission?
1. direct contact
2. no direct contact
3. transplacental
4. Blood-borne
31
What are the three nonhuman-human (excluding animal) modes of transmission?
1. Soil
2. Water
3. Fomites
32
What are the three animal to human modes of transmission?
1. Direct contact
2. Insect vector
3. Animal excreta
33
How is gonorrhea transmitted?
Direct contact
34
How is cholera transmitted?
No direct contact; fecal-oral route
35
How is congenital syphillis transmitted?
transplacentally
36
How is coagulase-negative staph transmitted?
blood-borne
37
How is tetanus transmitted?
spores from SOIL enter through wound in skin
38
How is Legionnaire's disease transmitted?
Bacteria in WATER aerosol are inhaled
39
How is a staph skin infection spread?
bacteria on an OBJECT are transferred to the skin
40
How is cat-scratch fever transmitted?
Direct animal contact
41
How is lyme disease transmitted?
via insect vector
42
How is Hemolytic-uremic syrndome transmitted?
via enterohemorrhagic E.Coli via cow feces in undercooked hamburger
43
How many microorganisms of TB do you need to cause infection? How does this compare to other bacteria?
ONLY 1-10 HOLY FUCKBALLS; next lowest is 10^2, ranging up to 10^8
44
What are the four characteristics of a successful pathogen?
1. Colonize
2. Immune evasion
3. Reproduce
4. Disseminate
45
What is the concept of pathogen virulence vs. host immunity?
Host and pathogen strike a balance that allows both of them to survive
46
Is death of the host a common event?
nope!
47
(blank) is a process whereby microbes attach to host cells or tissues.
adherence
48
(blank) is the asymptomatic harboring of microbes on or in the body; commensals as well as pathogens.
colonization
49
Do good bacteria also colonize us?
yes
50
How do we define infection?
epithelial barrier breached; some host damage caused by a microbe; can be subclinical.
51
What is a hospital acquired infection? how common is it?
nosocomial infection; 1:10
52
How do we define disease?
tissue destruction with specific signs and symptoms.
53
How do we define a pathogen?
a microbe with the inherent capability of causing infection and disease in a host with an
intact immune system.
54
opportunistic pathogens only cause disease in (blank) pt's
immunocompromised
55
What is the ability of a microorganism to produce infection and disease in the host?
pathogenicity
56
What is the quantitative measurement of pathogenicity?
virulence
57
(blanks) are gene products that enable a microbe to establish itself on or in a host
virulence factors
58
Strep salivarius is how virulent? Where is it found?
LOW virulence; oral flora; can cause septicemia in immunocompromised pts
59
E. Coli is how virulent? Where is it found? What can it cause?
MODERATE virulence; universal in the GI tract; can cause acute UTI
60
Bordetella pertussis is how virulent? What does it cause? Is it found in normal flora?
HIGH virulence; causes whooping cough; not in normal flora; causes disease in almost EVERY NONIMMUNE PERSON IT CONTACTS
61
Yersinia pestis is how virulent? What does it cause?
EXTREMELY FUCKING HIGH virulence; causes plague; death in a few days of 70% of untreated cases.
62
What is an extremely important diagnostic clue for determining what organism has infect the pt?
Incubation time; if they have symptoms three hours after event X, you know it can't be bug Y that doesn't show up for at least 12 hours
63
Salmonella spp. causes what and in what time?
food poisoning, bloody diarrhea; 16 hours - 2 days post ingestion
64
Shigella spp. causes what and in what time?
food poisoning, bloody diarrhea, 16 hours to 6 days post ingestion
65
S. aureus in food causes what and in what time?
secretes heat-stable enterotoxins; when in food will enter the blood
66
(blanks) promote attachment of bacteria to host cells or tissues
adhesins
67
Slime layers / glycocalyx / surface capsules prevent (blank)
phagocytosis
68
(blank) systems inject regulatory molecules and toxins into host cells, coopting cellular machinery/communication
secretion systems
69
Cytotoxic proteins, degradative enzymes, and superantigens are examples of (blank)
exotoxins
70
Gram negative bacteria produce this class of toxin
endotoxin
71
What are two types of structures that allow bacterial binding to human cells, such as E.coli to the uroepithelium?
Fimbriae or Pili
72
Collagen, Fibrinogen, Fibronectin, and Laminin binding proteins are all (blanks)
adhesins
73
T/F: capsules and slime layers promote bacterial adherence
true
74
What are the two mechanisms by which slime layers evade phagocytosis?
1. Inhibit access to PAMPs
| 2. Inhibit C3b deposition and access to deposited C3b
75
What is biofilm?
Bacterial cells embedded in extracellular polymeric substance (EPS)
76
What makes up EPS of biofilm?
extracellular DNA, proteins, and polysaccharides
77
What is the order of membranes in E. Coli from inside to outside?
1. Plasma membrane
2. Periplasmic space
3. Outer membrane
78
What are the three steps in biofilm development?
1. Attachment
2. Growth
3. Dispersal
79
What are the five functions of biofilm?
```
ARE RAT
Adhere to environmental surfaces
Resist flushing
Enhance immune evasion
Resist antibiotic treatments
Associate with other bacteria
Trap nutrients for bacterial growth
Trap nutrients for growth
```
80
What is the most common type of bacterial secretion system?
Type 3 Secretion System (T3SS)
81
Explain the overall form of the T3SS?
Secretion apparatus is assembed in the BACTERIAL cell wall that polymerizes to form a hollow "needle" to penetrate the host cell membrane
82
What is another name for the secretion system?
injectosome
83
what is an invasin?
protein that promotes bacterial invasion of tissues or cells
84
T/F: invasins can be extracellular or intracellula proteins
TRUE, extra: hyaluronidase of Strep pyogenes
| intra: IpaB of Shigella flexneri
85
T/F: some bacteria multiply in the phagolysosome
true
86
What are three methods of bacteria invading a cell?
1. Bind to cell receptors and induce their own endocytosis
2. Escape the vacuole
3. Multiply in phagolysosome
87
What is transcytosis?
Bacteria moving through the cell and escaping into the submucosa
88
Are endotoxins secreted?
NO they are teh LPS on the outer membrane of grame negative!
89
Are exotoxins secreted?
Yes!
90
Where do you find exotoxins?
Secreted into the environment or bound to the microbial surface
91
Are exotoxins are specific or nonspecific?
somewhat specific, they have to bind to certain receptors
92
T/F: Exotoxins stimulate an Ab response
TRUE, they're called antitoxins
93
What is a toxoid and how is it different from a exotoxin?
Toxoids are antigenic (create Ab response) but not toxic (like the Tetanus toxoid vaccine)
94
What are the four classes of exotoxins?
1. Cell surface active
2. membrane damaging
3. intracellular
4. Extracellular damaging
95
Superantigens like toxic shock syndrome toxin is a class (blank) exotoxin
type 1
96
Clostridial alpha toxin that has phospholipase acivity is a type what exotoxin?
membrane damaging
97
AB toxins like cholera toxin is a type what exotoxin?
intracellular
98
hydrolytic enzymes such as hyaluronidase and collagenase are what type of exotoxin?
extracellular damaging
99
What portion of the cholera toxin is catalytically active?
A1
100
What is the structure of cholera toxin subunits?
A1A2(B)5
101
In cholera toxin, A1 ADP-ribosylates protein Gs which results in continuous activation of (blank)
adenylate cyclase
102
In cholera, high cAMP activates the (blank), causing a huge efflux of ions and water (diarrhea)
cystic fibrosis transmembrane regualtor (CFTR)
103
What ions are lost during cholera induced diarrhea?
Na, Cl, K, and HCO3
104
What type of PM receptor does choleratoxin bind to?
ganglioside receptor
105
Superantigens bind simultaneously to T cell receptors and MHC class II molecules (oustide/within) the normal peptide-binding groove.
outside
106
superantigens can cause a cytokine (blank)
storm
107
Up to (blank) % of all peripheral T cells can be stimulated by a superAg
20%
108
What are the two superAg responses associated with S. aureus?
```
Toxic shock syndrome toxin (TSST)
Staphylococcal enterotoxins (SEA)
```
109
What is the superAg associated with S. pyogenes?
streptococcal pyrogenic exotoxins (SpeA)
110
Can a superAg bind without a peptide being bound to MHC?
yes
111
What class of MHC does a superAg bind to?
MHCII
112
Does the superAg bind to the B or A chain of the TCR?
B
113
What is the toxic component of LPS?
lipid A
114
What does lipid A cause?
overproduction of cytokines like tNF-a and other inflammatory mediators
115
What cell does lipid A stimulate?
macrophages
116
what are the symptoms of the inflammatory mediators released by lipid A stimulation?
sepsis
and septic shock; fever, hypotension, disseminated
intravascular coagulation (DIC), and multi-organ
system failure (MOSF).
117
LPS activates the (blank) cascade resulting in DIC and ARDS
coagulation cascade
118
LPS activates the (blank) cascade, resulting in increased vascular permeability
complement cascade, along with release of prostaglandins and leukotrienes
119
T/F: LPS can activate the MBL complement system
False, it activates classical and alternate pathways
120
T/F: endotoxins are highly antigenic
false, they are POORLY antigenic
121
Is LPS presented directly to the macrophage?
No, it must first bind LPS binding protein and then can be recognized by TLR-4 on the macrophage
122
T/F: biofilms can allow pathogens to better adhere to surfaces like medical equipment, catheters, etc.
true
123
What normal skin bacteria can form a biofilm and cause systemic disease if introduced to the blood?
s. epidermis
124
Panton-Valentine leukocidin is a cytotoxin found in some strains of (blank)
S. aureus, especially MRSA
125
Pyrogenic exotoxin is produced by group (blank) strep.
group A
126
Streptokinase is produced by group (blank) strep
group A
127
B-lactamase activity would confer what ability to bacteria?
penicillin resistance!
128
Environmental factors such as (blank 3x) may control expression of virulence genes
temp, pH, and osmolarity
129
diphtheria toxin is regulated by (blank) concentrationj
iron
130
Borrelia burg. surface protein expression is regulated by (blank)
temp
131
V. cholerae toxin is regulated by (blank 2x)
pH and temp
132
How does iron regulate diphtheria toxin?
iron-dependent repressor protein turns off transcription at high iron levels
133
Quorum sensing is the release of (blanks) by individual bacteria to change gene expression when the colony hits a certain density
autoinducers
134
What is the big picture reason for quorum sensing?
facilitates coordinated responses between bacteria
135
What are the specific actions induced during quorum sensing?
biofilm formation
virulence factor secretion
sporulation
competence for DNA uptake
136
The Agr system of S aureus is used in what process?
quorum sensing
137
The expression of (blank) factors makes a pathogen pathogenic
virulence factors
138
T/F: The complete gene sequence (genome) of virtually every human pathogen is known.
true
139
T/F: Different isolates of the same bacterial species can have widely different virulence characteristics.
True
140
T/F: there are some virulence factors that are present on all isolates of a given species
true
141
what are mobile genetic elements?
plasmids, bacteriophages, and pathogenicity islands (PAIs)
142
E. coli enterotoxins are encoded by what type of moblie genetic element?
plasmid
143
Adherence factors for mucosal invasion of E. coli and Shigella are encoded by what type of moblie genetic element?
plasmids
144
pXO2 capsule factors and pXO1 edema/lethal/protective factors essential for virulence of B. anthracis are encoded by what type of moblie genetic element?
plasmid
145
Shiga-like toxins that inhibit protein synth by E. coli are encoded by what type of moblie genetic element?
phage
146
Cholera toxin is encoded by what type of moblie genetic element?
phage
147
strep pyrogenic exotoxins are encoded by what type of moblie genetic element?
phage
148
Type III secretion systems and effector proteins of E. coli are encoded by what type of moblie genetic element?
PAI
149
TSST superAg is encoded by what type of moblie genetic element?
PAI
150
R28 adhesins of strep pyogenes are encoded by what type of moblie genetic element?
PAI
151
How do most bacterial plasmids replicate?
extra-chromosomally
152
What is the range of size in kb of plasmids?
one to hundreds of kb
153
T/F: a bacteria can have multiple plasmids
true
154
T/F: plasmids play an essential role in B. anthracis virulence
true
155
what B. anthracis plasmid codes for toxin components?
pXO1
156
what B. anthracis plasmid codes for capsule biosynth?
pXO2
157
What are the two types of life cycles of a bacteriophage?
lytic or lysogenic
158
Do lytic or lysogenic phages encode virulence factors like the Shiga-like-toxin of ETEC?
lysogenic
159
T/F: some pathogens have no integrated phage while others have up to 10% of the chromosome as phage
true
160
Lysins are currently being studied as anti-(blanks)
bacterials
161
What are pathogenicity islands?
clusters of genes on the bacterial chromosome which code for virulence factors
162
PAIs are important in (blank) gene transfer via conjugation
horizontal gene transfer
163
What percent of the bacterial genome is made up of PAIs?
10-20%
164
What does the locus of enterocyte effacement (LEE) of E. coli code for?
multiple virulence factors
165
What determines an E. coli pathotype?
mobile genetic elements
166
What strain of E. coli is the cause of traveler's diarrhea and leading cause of diarrhea in the developing world?
ETEC enterotoxigenic E coli
167
What mobile genetic element does ETEC contain?
pENT= enterotoxin-encoding plasmid
168
What distinguishes EPEC enteropathogenic E coli from ETEC?
EPEC causes diarrhea but the virulence mechanism is unrelated to normal E. coli enterotoxins
169
What mobile genetic element does EPEC contain?
pEAF= EPEC adherence factor plasmid; LEE PAI
170
EHEC enterohemorrhagic E coli produces what symptoms, leads to what syndrome, and is important in what organ failure in children?
causes diarrhea or hemorrhagic colitis; progresses to hemolytic uremic syndrome (HUS), causes renal failure in children and morbidity and mortality in adults
171
What mobile genetic elements does EHEC contain?
LEE PAI; Stx phage = Shiga-toxin encodiing phage
172
EIEC enteroinvasive E. coli produces a syndrome that is identical to (blank)
Shigellosis; profuse diarrhea and high fever
173
What mobile genetic element and abnormlity does EIEC contain?
invasion plasmid and a black hole of deleted genes
174
UPEC uropathogenic E. coli causes (blank)% of uncomplicated UTIS
80%
175
what mobile genetic element does UPEC contain?
Unknown PAIs
176
T/F: mobile elements can influence virulence factor production
true
177
Treating EHEC with antibiotics can increase the incidence of (blank)
HUS hemolytic uremic syndrome
178
What is the cause of HUS?
rapid and premature destruction of RBCs; clogs the glomerulus leading to kidney failure
179
T/F: Antibiotics have no effect on Shiga-like toxin production by EHEC
false; they INCREASE it
180
What are the two mechanisms by which it is thought that antibiotic therapy increases toxin release in E. coli?
1. Lysis of bacteria releases more toxin
| 2. Increased gene transcription of toxins post phage induction
181
During the SOS response of EHEC, what protein binds to repressors to allow toxin gene transcription in the lytic cycle?
RecA
182
What are all the mechanisms by which bacteria evade the immune system?
```
Encapsulation
Antigenic mimicry
Antigenic variation
Anti-Ig proteases
Destruction of phagocytes
Intracellular replication
Inhibition of chemotaxis
Inhibition of phagocytosis
Inhibition of phago-lysosomal fusion
Resistance to lysosomal enzymes
```
183
what are the mechanisms that group A strep uses to thwart the immune response?
1. Antimicrobial peptide resistance
2. Degradation of NETs
3. Phagocyte lysis
4. Chemokine degradation
5. Nonopsonic binding/Ab degradation
6. Cloaking of opsonins
7. Complement deposition interference
8. Phagocyte uptake impairment
184
What is the mechanism by which GAS evades complement deposition?
Hyaluronic capsule, fibrinognen, Factor H, and M protein prevent adherence
185
What is the mechanism by which GAS cloaks opsonins?
Fibronectin and Fibrinogen, M protein, M-like proteins, Sfb1
186
What is the mechanism by which GAS causes Ab degradation?
SpeB, EndoS, and Mac 1/2
187
What is the mechanism by which GAS causes nonopsonic binding?
M protein, protein H, Sfb1
188
What is the mechanism by which GAS causes chemokine degradation?
ScpA for C5a
| SpyCEP for IL-8
189
What two molecules are used by GAS to cause phagocytic lysis?
SLS and SLO
190
What is the DNase used by GAS to degrade NETs?
Sda1
191
What proteins are used by GAS for antimicrobial resistance?
SIC, DltABCD, SpeB
192
Mac from GAS has homology to the alpha subunit of leukocyte B2-integrin, aka (blank)
CD11b
193
Mac from GAS can bind to (blank) on the neutrophil surface inhibiting phagocytosis and activating the oxidative burst
CD16
194
Bacteria modify their surface proteins to evade (blank)
opsonization
195
What is phase variation? What bacterial protein is a good example of it?
Expression of surface proteins are switched on or off, such as in Neisseria pili protein
196
What is it called when surface antigens are switched from one type to another?
Antigenic variation, also seen in Neisseria pili
197
What are the two mechanisms of phase variation?
1. Site specific variation
| 2. Slipped-strand mispairing
198
What are the two mechanisms of antigenic variation?
Homologous recombination from silent to transcribed and slipped strand mispairing
199
Genetic change in bacteria is brought on by phase (and/or/both) antigenic conversion
BOTH
200
Intracellular bacterial pathogens avoid what type of immunity?
humoral
201
What are the three methods by which bacteria are capable of escaping death even after phagocytosis?
1. inhibition of phagosome-lysosome complex
2. resistance to lysosomal enzymes
3. escape from phagolysosome
