module 4.1 Flashcards
(220 cards)
1
Q
What are the three generalized steps of successful bacterial infection?
A
1) Colonization
2) Spread
3) Persistence
2
Q
at what general step does the population of bacterial cells increase exponentially?
A
colonization
3
Q
what is an accidental pathogen and what is an example of one?
A
An accidental pathogen is a pathogen that does not mean to enter the body but does.
Example: Legionella
4
Q
what kind of pathogen is an STD?
A
intracellular obligates - STDs only stay between humans
5
Q
what other reasons, besides to infect, are virulence factors used for mainly?
A
To survive the extracellular environment
e.g., other bacteria, antibiotics, UV light, etc.
6
Q
bacterial pathogens are bacteria specialized for …
A
evading the immune system
7
Q
what are the 4 major problems bacteria face in the environment?
A
1) Sequestration of iron
2) Adhesion sites
3) Exposure to noxious chemicals
4) exposure to sunlight and extreme weather
8
Q
what kind of pathogens contain larger genomes, and why?
A
nonobligate, host-associated, and free-living microorganisms contain larger genomes than an intracellular obligate pathogen would because they need more tools to be able to survive freely in the environment
e.g., more fimbriae
9
Q
what is the importance of endospores?
A
endospores protect bacteria against deleterious situations/ conditions, i.e., preserve bacteria’s genetic material from any external environmental factor
10
Q
what bacteria are known for producing endospores?
A
1) bacillus
2) clostridium
11
Q
what other mechanisms besides the formation of endospores, do bacterial pathogens have to protect against external damage?
A
DNA repair, efflux pumps, change in membrane properties, and detoxification
12
Q
What are biofilms?
A
extracellular matrices/ gooey layers produced by bacteria that have colonized a surface. contains carbohydrates, proteins, and maybe even DNA that would form filaments to hold everything together
13
Q
biofilms are a constant source of …
A
PAMPs- causes constant activation of the immune system
14
Q
what is the level of resistance of biofilms?
A
very much resistant - resistant to antibiotics, disinfectants, and predators for the most part
15
Q
what bacterial pathogens are able to cause the formation of biofilms in humans?
A
- pseudomonas aeruginosa
2. staphylococcus viridans
16
Q
what infection is pseudomonas aeruginosa responsible for?
A
cystic fibrosis - formation of biofilms on lungs
17
Q
what is the significance of staphylococcus viridans?
A
commensal bacteria, form biofilms/plaque on teeth
18
Q
what is the main way biofilms are transmitted?
A
transmitted from medical devices such as a catheter. if too much biofilm enters the bloodstream it will cause septic shock
19
Q
what is the significance of flagella?
A
produced by bacteria to swim through liquids and travel through viscous medium
20
Q
what virulence factor contributes to the production of flagella
A
motility- critical for bacterial pathogens to reach their preferred site of infection
21
Q
what receptors in the host are flagellins recognized by?
A
TLR5 and NOD-like receptors - PAMPS
22
Q
Flagellins are highly …
A
antigenic
23
Q
because flagellins are highly antigenic, what do bacterial pathogens do in order for successful infection?
A
tightly regulate the production of flagellins, stopping production once they are inside the host
e.g., phase variation used by Salmonella to trick the immune system
24
Q
how do Treponema pallidum and Borrelia burgdorferi regulate their flagellin?
A
flagellum stays in the periplasmic space once inside the host
25
what infection is Treponema pallidum responsible for?
syphilis
26
what disease does Borrelia Burgdorfer cause?
lyme disease
27
how do flagellum move in Treponema pallidum?
moves in a screw-like motion - to penetrate the host membrane
28
bacteria use ... as ways to penetrate the skin
vectors
29
what are examples of bacteria that use vectors to penetrate intact skin?
1. Yersinia pestis, bypasses the skin layer and enters the bloodstream by a flea bite
2. Borrelia Burgdorfer - uses ticks to cross the skin barrier, causing lyme disease
30
where does Yersinia pestis come from?
rodents
31
how is yersinia pestis transmitted from rodents to humans?
infected rodent transmits the bacterial pathogen to an insect that bites the rodent. The infected insect (flea vector) then bites humans causing outbreaks
32
what is the main cause of yersinia outbreaks?
living in densely populated areas that have a lot of rodents running around
33
why was it so easy for scientists to recover the whole genome of yersinia pestis and study its evolution?
there were huge outbreaks which gave scientists a large source of infected individuals to put together a genome. yersinia pestis outbreaks also occured for a very long time so scientists were also able to study the genomic changes from infected individuals from different periods of time
34
Lyme disease transmission
transmission runs through deer and rodents which ticks feed on. these infected ticks are then able to survive for a while in the environment. they then latch on to pets and humans transmitting Lyme disease.
35
what virulence factor in bacteria allows for sufficient attachment to host cells?
production of adhesins
36
what are adhesins?
protein structures that recognize a molecule of the host and bind to it
37
what are the two categories of adhesins?
1. pili
| 2. afimbrial adhesins
38
what kind of response does the attachment of the pathogen to the host cell trigger?
a transcriptional response
39
what types of pili exist?
1. thin filament
2. curly pili, aggregation
3. type IV pili, rope-like
40
what is the structure of gram-negative pili?
rod-shaped filamentous protein structures. a whole variety differing in thickness and length
41
what are the protein-subunits of pili?
pilin. polymerization of these protein subunits forms pili.
42
how are pilin subunits packed?
packed in an ordered fashion, into a helical array to form a flexible cylindrical structure
43
what section of the pilus is the actual adhesin?
the tip. recognizes and attaches to a molecule on the surface of host cells
44
definition of tropism?
the specificity an adhesin of a particular species of bacteria, has for a particular host protein. contributes to host cell- or tissue-specific interaction. only the body sites expressing the specific molecules will be infected
45
what are typical targets of adhesins?
carbohydrate residues (sialic acid), glycoproteins, and glycolipids
46
what system assembles most pili?
the chaperone-usher system
47
how does the chaperone-usher system work?
consists of protein synthesis in the cytoplasm, proteins are secreted into the periplasm where they're ushered via chaperones along with other synthesized proteins, assembling the pili. the adhesive tip structure is assembled first, then the shaft of the structure and then a termination protein that stops the polymerization process.
48
what are the properties of pili of gram-negative bacteria?
bacteria constantly lose and re-form pili. they can be easily broken off by mechanical shearing.
49
why is losing and re-forming pili for bacteria beneficial?
if host antibodies are bound to the adhesin of the pilus, which blocks binding to host cells, and that pilus is then lost, the antibody will also de-attach from the bacterial cell membrane and form a new pilus with no antibiotic on it. increases the bacteria's chance of evading the immune system.
50
why do gram-negative pili help bind to host cells?
if the host membrane is also negatively charged, the pilus is able to overcome the electrostatic repulsion present between the gram-negative bacteria and the host cell. the pilus does this by mediating loose binding to host cells, keeping the bacteria and host cell initially at a distance. when surface adhesins are produces, they will then mediate closer attachment
51
What is Type IV pili?
a special type of fimbriae that is not made via the chaperone-usher system. It is made in the inner membrane and the shaft component protrudes through the periplasm and the outer membrane.
52
what is the significance of type IV pili's shaft?
can extend (polymerize) and de-extend (depolymerize). once attached to a host cell, the shaft will depolymerize, bringing the host cell closer to the bacteria, using the PilA component.
53
what are the characteristics of pili in gram-positive bacteria?
short and thin
54
what kind of molecular bond is formed between gram-positive pili?
covalent bond
55
covalent attachment of gram-positive pili to the peptidoglycan layer occurs via ...
sortase - a protein only in gram-positive bacteria
56
what motif mediates the attachment of pilin subunits to the peptidoglycan cell wall
LPXTG motif
57
what are nonfimbrial adhesins?
bacterial surface proteins that mediate attachment to the host cell surface
58
what type of ligands on host-cell surfaces mediate attachment of host cells to surrounding tissues?
integrins and cadherins - interact with the extracellular matrix
59
what two surface proteins do listeria monocytogenes use to bind to host cells?
internalin A and internalin B
60
yersinia pestis invasin binds to ...
alpha5beta1-integrin
61
invasin alpha5beta1-integrin shares structural features with ...
fibronectin, the natural host ligand of alpha5beta1-integrin
62
what does internal A bind to? (Listeria)
E-cadherin (tight junction)
63
what does internalin B bind to?
the receptor for the subunit C1q (receptor gC1qR) of the complement protein C1 , located on the host cell surface
64
... is one of the least understood virulence factors?
penetrating and moving through the mucin layer to reach the underlying epithelial cell layer
65
the layer of mucin is not a ...
uniform mat - bacteria that can produce enzymes to degrade the mucin layer still consists of a long process because of the complexity of the mucin layer
66
mucin is secreted by __ cells
goblet cells
67
what cells can bacteria travel through, overtaking the mucin layer?
M cells - not covered by a thick mucin layer because they are not closely located to goblet cells
68
what is the significance of H. pylori regarding the mucin layer?
able to penetrate through the mucin layer, by increasing the mucin's pH . the increase in pH causes the mucin to de-gel, allowing the bacteria to travel through and reach the gastric epithelium
69
what enzyme do H. pylori use to raise the mucin's pH?
urease - converts urea to ammonia, neutralizing the gastric acid
70
inflammation due to H.pylori invasion is due to ___ components
gastric acid, proteases, and effector molecules released by H. pylori
71
what is the significance of the production of ammonia produced via urease by H. pylori?
neutralizes the gastric acid and results in mucosal cell death along with production of cytokines due to inflammation
72
what is the mechanism role of sIgA?
simultaneously binds to the bacterial antigen via their antigen-binding sites and interact with mucin via their Fc portion - effectively traps bacteria in the mucin layer
73
what is bacterial mechanism against sIgA?
production of an sIgA protease - cleaves sIgA at the hinge region which separates the part of sIgA that binds to mucin from the part that binds to the antigen
74
the mucus layer contains ___ secreted by underlying host cells.
Antimicrobial peptides (AMP)
75
4 mechanisms of resistance to AMP by bacteria:
1. capsule (isolation from AMP)
2. LPS or LTA/TA modification (addition of a positive charge)
3. peptidases
4. efflux pumps
76
once pathogenic bacteria evade the immune system, they can __
grow and acquire nutrients
77
how do some bacteria avoid the recruitment of phagocytes?
produce enzymes that degrade C5a
78
what source of PAMPs can bacteria modify to be less recognized by the host immune system?
LPS - causes a reduction of the host response
79
some bacteria produce ___ that kill phagocytes, prevent their activation, inhibit their migration, or reduce the strength of the oxidative burst
toxins
80
what toxin do H. pylori produce?
VacA
81
what different roles can VacA perform?
effects on cell signaling, pore formation in the cell membrane, vacuolation, apoptosis, etc.
82
what is the significance of capsules?
forms a protective coating around bacteria - an unstructured network of polymer
83
what immune system components does the capsule protect bacteria from?
lysosomes, antimicrobial peptides, phagocytosis (opsonization and digestion), and the complement system
84
how does the capsule protect against the complement system?
capsules have a low binding affinity for the B factor or have a preference for the H factor (B factor located on complement proteins, i.e., C3b, C5b)
85
what is an effective host response against encapsulated bacterial pathogens?
producing antibodies that bind to the capsule and promote phagocytosis and activation of the complement by the classical pathway
86
capsules that resemble ___ are poorly immunogenic
host polysaccharides
87
___ serve as a site of attachment for C3b
LPS
88
what do bacteria attach sialic acid to, in order to inactivate C3b (H/I factor)
LPS O antigen
89
what is the significance of bacteria expressing long O antigens?
to cause the MAC complex to form far away from the bacterial membrane and render it ineffective
90
what mechanism allows for evading the host's antibody response?
antigenic variation, capsule resembling host polysaccharide, and coating of bacteria with host proteins
91
definition of intracellular pathogens
bacteria that live inside the host cells
92
some bacteria have evolved ways to invade non-phagocytic cells by inducing ___ reorganization by using ___ or ___
actin
| invasins or T3SS
93
example of non-phagocytic cells
mucosal cells
| epithelial cells
94
what occurs inside the host cell when Listeria's internalin A (InlA) component binds to E-cadherin and its InlB component binds to gClqR?
actin cytoskeleton rearrangements and signaling
95
why are bacteria like Yersinia and Mycobacterium considered such dangerous bacterial pathogens?
they are able to overcome the phagocyte's strategies to kill bacteria
96
what is the host cell response to pathogens who are trying to overcome phagocytosis?
activation of the macrophage response (mediated by T-helper cells) and the CTL response
97
what are the bacterial strategies for resistance to phagocytosis?
1. neutralization of the phagolysosome components: capsule, surface modification, proteases, peptidases, resistance to low pH
2. resistance to reactive oxygen species: production of catalase, superoxide dismutase, surface polysaccharide and proteins that detoxify oxygen radicals
3. prevention of phagolysosomal fusion
4. escape from the phagosome
98
how does legionella stop the acidification of the phagosome and the maturation process?
prevents acidification of the phagosome and eliminates phagosome surface proteins needed for the fusion with lysosomes
99
how does salmonella prevent phagolysosomal fusion?
actively remodels the endosomes at an early stage of maturation (after invasion of M cells)
100
how does mycobacterium tuberculosis (Mtb) prevent phagolysosomal fusion?
enters the phagocytes by binding to the receptor for activated C3b. It then recruits the host cell protein TACO, to the phagosome to block fusion with the lysosome
also prevents acidification, oxidative burst, and production of Il12 (Il12 normally activate Th1 response)
101
What is dissemination?
the action of cell-to-cell spreading by producing actin, known as actin-based motility. allows pathogens to completely avoid the antibody-mediated response; there is no extracellular phase during infection.
polymerization of actin to push the bacterium forward
102
dissemination also involves the production of ___ & ____ degradative enzymes to destroy cells
ECM (proteases, hyaluronidases) and toxins to destroy cells
103
what is the significance of the production of plasminogen activator?
induces degradation of fibrin clots and allows the bacteria to escape blood clots (streptokinase)
104
what does the production of DNAse do?
destroy NETs
105
most bacteria require ___ for growth
iron
106
what bacterial pathogen does not use iron for growth?
Borrelia burgdorferi - lacks all the iron-dependent cofactors and enzymes and uses MANGANESE instead of iron for the chemistry it needs for survival and replication
107
what are siderophores?
small molecules that have a high affinity for iron, even higher than the host's affinity
108
what do siderophores do?
excreted out of bacterial pathogen's membrane, acquires iron, and re-enters the bacterial cell by binding to the iron-siderophore receptor, and traveling back through a channel
109
bacteria that are dependent on co-infection for the acquisition of iron do what?
produce receptors for siderophores produced by other bacteria
110
besides producing siderophores and relying on other infections to be present, what else can bacterial pathogens do to acquire iron?
use the iron-binding protein of the host as a source of iron. bacterial receptors bind to the host iron-binding proteins (lactoferrin, transferrin)
111
____ pathogen is able to take up iron directly from heme
staphylococcus aureus
112
what is the benefit of pathogens inducing toxins inside the cell?
acquiring nutrients, evading the host immune system, or creating an optimal niche for growth
113
what is BoNT, and what does it cause?
botulinum neurotoxin. causes flaccid paralysis which leads to death due to the collapse of the respiratory system
114
why is it hard to understand the benefit of BoNT?
after the toxin enters the host, there is no infection of C. botulinum and the pathogen is rapidly eliminated from the body
115
where are most toxin genes found?
on PAIs, prophages and other mobile genetic elements
116
what is the major driving force in the evolution of toxins and toxin-producing bacteria?
HGT (horizontal gene transfer)
117
what organisms are the likely targets of toxins, that happen to also affect humans?
animals, lower eukaryotes, insects and protozoa
118
the C. diphteriae toxin is carried on a ____
prophage
119
toxins are categorized based on their ...
target, characteristics and structure, the disease they cause, and their mode of action
120
two general categories of toxins
1. endotoxin: part of the bacterial pathogen
| 2. exotoxin: secreted into the surrounding as the bacterial pathogen grows
121
categorizations by mode of action:
- type I toxin: binds to the target cell surface and acts extracellularly (ex. superantigen)
- type II toxin: binds to the target cell surface and acts on the eukaryotic cell membranes
- type III toxin: AB type toxin, binds to the target cell surface, enters the host cells, and activates or inactivates intracellular targets
122
endotoxins (nonprotein)
integral membrane components of bacteria such as LPS, LTA/TA, and peptidoglycan. both in gram negative and positive bacteria.
released from bacterial cells during replication and when they lyse.
weakly antigenic but highly immunogenic
produce general systemic effects
123
what is septic shock?
a state of multisystem organ hypofusion (low blood pressure) which deprives organs of nutrients and oxygen
124
what bacterial infections usually cause septic shock?
septicemia
125
what are the four clinical stages of septic shock?
1. systemic inflammatory response syndrome (SIRS): fever or hypothermia, high heart rate and high respiratory rate
2. Sepsis: SIRS + documented septicemia (presence of bacteria in the bloodstream)
3. severe sepsis: organ dysfunction and low blood pressure. at this stage 70% of patients die
4. septic shock: low blood pressure despite administration of fluid
126
what is the mechanism of septic shock?
bacteria lyse, LPS are released, LPS bind to LPS binding protein, LPS and the LPS binding protein attach to the CD14 receptor on the macrophage inducing interleukins, activation of the complement cascade, and activation of the coagulation cascade
127
what syndrome does activation of the coagulation cascade cause?
acute respiratory distress syndrome
128
what toxin does Bordetella pertussis produce?
tracheal cytotoxin (TCT, peptidoglycan subunit)
129
what does tracheal cytotoxin cause?
arrest of cilliary movement, cell death and release of IL-1 (pro-inflammatory) - cause of whooping cough
130
what kind of toxin is the tracheal cytotoxin?
an endotoxin, nonprotein
131
what kind of toxin is mycolactone?
an endotoxin, nonprotein
132
what does Mycobacterium ulcerans cause?
buruli ulcers, a chronic infection leading to necrotic lesions
133
mycolactone is a diffusable ___ toxin
lipid
134
lesions caused by mycolactone are characterized by ...
little inflammation and no physical pain
135
what kind of pathogen is M. ulcerans?
an intracellular pathogen that grows inside the macrophages and in necrotic tissues
136
what are type 1 exotoxins (protein toxins)? what do they do?
Superantigens: triggers uncontrolled, massive activation of T cells and APCs, leading to massive release of cytokines and shock
137
what syndrome do superantigens cause?
toxic shock syndrome and food poisoning
138
what is the cause of toxic shock syndrome?
tampons
139
what are type II exotoxins (protein toxins)?
membrane-disrupting toxins
140
what are the three different roles of membrane-disrupting toxins?
1. kill host cells
2. destroy the phagosome and enter the host cell cytoplasm
3. exit cells after intracellular replication
141
what are the two types of membrane-disrupting toxins?
1. pore-forming toxins
| 2. phospholipase
142
what do pore-forming toxins do?
forms a channel in the host membrane, leading to a sudden inrush of water and cell lysis
143
what are the two types of pore-forming toxins?
1. alpha-pore-forming toxins
| 2. beta-pore-forming toxins
144
what do alpha pore-forming toxins do?
form alpha helices that penetrate the membrane
145
what do beta pore-forming toxins do?
form beta sheets that form beta barrels in the membrane (requires oligomerization)
146
what is an example of a pore-forming toxin?
streptolysin - comes from streptococcus pyogenes
147
what bacteria use pore-forming toxins?
S. pneumoniae - toxin: pneumolysin
148
what does phospholipase do?
destroys the integrity of the host cell membrane phospholipids - lysis of host cells
149
what bacterial pathogen uses phospholipase?
listeria
150
what are AB toxins?
type 3 exotoxins, composed of 2 subunits (enzymatic subunit A, binding/cell entry B)
151
what does the A subunit of AB toxin do?
modifies a target inside the host cell leading to damage to the host
152
what does the B subunit of AB toxin do?
binds to specific cell receptors providing tissue/cell type specificity
153
how are the two subunits of the AB toxin linked?
covalent disulfide bond
154
what is the bond between multisubunit AB toxin?
non-covalent interactions, which are disrupted when the toxin is internalized
155
how do AB toxin cells enter the host?
endocytosis
156
how is endocytosis mediated of AB toxins into the host cell?
endocytosis requires the passage of the A subunit through the membrane of the endosome, usually mediated by the B subunit
157
how do anthrax toxins (a type of AB toxin), enter the host cell?
oligomerization of the B subunit on the surface of the host cell, binding of the A subunits to the B domain, and the endocytosis and passage of A subunits through the pore
158
What is the effect of the Diphteria toxin?
colonizes the throat via C. diphteriae that carry the lysogenic corynebacteriophages. causes considerable damage to the mucosa of the throat and also cause skin infections via wounds
159
what does ADP-ribosylation cause?
inactivation of the protein or a change in its activity
160
what toxin catalyzes ADP-ribosylation of host cell proteins?
the A subunit of the AB toxin
161
what are the two targets of ADP ribose during ADP-ribosylation?
- EF-2: stop protein elongation (death)
- Gs protein: regulates cyclic AMP levels, cell loses control of ion flow and results in massive loss of water when ADP ribose binds to the protein
162
What bacterium causes botulism?
Clostridium botulinum, anaerobe
163
how does botulism spread?
germination of C. botulinum's spores
164
what is the toxin produced by botulism?
BoNT - neurotoxin
165
what are the characteristics of BoNT?
- 7 serotypes
- very potent: lethal dose is 1-5 ng/kg
- recovery takes 4-6 months
166
what are the three types of botulism?
1. food-borne botulism
2. infant botulism
3. wound botulism
167
what is the mode of action of BoNT?
1. BoNT binds to the motor neuron receptor, specifically the heavy chain to the receptor, and endocytosis into the motor neuron
2. LC, an endoprotease that is part of BoNT, is translocated from the vesicle via the N-terminal portion of the heavy chain which forms a channel in the vesicle membrane, into the cytoplasm of the motor neuron
3. LC then cleaves SNARE proteins which prevents Acetylcholine being released into the muscle cell - this process prevent muscle contraction, i.e., flaccid paralysis
168
LC's from different BoNT ___ target different ___ proteins
serotypes
| SNARE
169
What is tetanus?
an infection coming from clostridium tetanii, found in the soil as a spore
170
what is the impact of the toxin, TeNT, that tetanus produces?
enters the blood stream, acts on the neurons, causing spastic paralysis, i.e., constant muscle contraction
171
what is the mechanism of TeNT?
targets inhibitory synapses of the CNS and undergoes retrograde transport to the inhibitory neuron
172
what happens during TeNT transcytosis?
TeNY inhibits Glycine secretion so the contracted muscles never receive a signal to stop muscle contraction
173
what specific SNARE protein does TeNT affect?
VAMP2
174
what is the treatment of tetanus?
1. vaccination
2. antitoxin (passive immunization)
3. antibiotics + cleaning of the wound
4. muscle relaxant + curare (block the Ach receptor)
175
what are secretion systems?
virulence factors of bacteria, that allow the bacteria to interact with and modify their surrounding environment. secretion systems also allow bacteria to transport virulence proteins (toxins)
176
what is the role of protein secretion systems?
transports adhesins (surface factors), toxins, exoenzymes, proteases, and other virulence factors onto the cell surface, for release into the medium and direct delivery inside the host cells
177
the protein secretion system of gram-negative bacteria are more ___, more ___, and more ____ than those of gram-positive bacteria
numerous
complicated
diverse
178
what is the basic secretory system (Sec system)?
a secretion system used by both gram-negative and gram-positive bacteria to translocate proteins across the cytoplasmic membrane
179
the Sec system transports ___ proteins
unfolded
180
where is the signal sequence located on proteins that are transported via the Sec system?
N-terminus
181
what are the proteins involved in Sec system?
SecB, SecA, SecYEG, SecDF, YajC
182
what is the function of SecB?
a chaperone that binds to signal sequences and keeps the protein to be secreted in an unfolded state
183
what is the function of SecA?
is an ATPase that provides some of the energy needed for translocation. the proton motive force or translocation provides the rest of the energy needed.
184
what complex do the SecYEG proteins make up?
the heterotrimeric complex
185
what is the role of the heterotrimeric complex?
forms a protein-conducting channel through the cytoplasmic membrane
186
what is the function of SecD, SecF, and YajC?
help to stabilize the whole complex
187
what is the overall mechanism of the Sec system?
SecB transports the unfolded protein to SecA where it'll be translocated across the membrane through the heterotrimeric complex (SecYEG proteins). YidC attaches the the heterotrimeric complex to act as an accessory protein that helps translocation. After the unfolded protein is exported, it attaches to SPase, located in the membrane, and where it is cleaved.
188
what is the Twin-arginine transport (TAT) system?
secretory system used by both gram-negative and gram-positive bacteria to translocate FULLY FOLDED proteins to the periplasm / surrounding medium
189
how is energy provided in the TAT system?
proton motive force across the membrane
190
what are secretion systems specific to gram-negative bacteria?
secretion systems used to cross the outer membrane
191
what are the two categories of secretion systems specific to gram-negative bacteria?
1. sec-dependent
- type 2, type 5
2. sec-independent
- type 1, 3, 4, 6
192
what is the type 2 secretion system (T2SS) and what is its general mechanism?
also known as the general secretion pathway. unfolded proteins transported into the periplasm via the Sec pathway, followed by the protein PulA being secreted by T2SS.
193
how are cholera toxins secreted through the T2SS?
A and B subunits are translocated separately from each other via the Sec system, followed by the formation of the toxin (bonding of A and B subunits) in the periplasm. the resulting cholera toxin is then translocated across the outer membrane via PulD and PulS protein complex
194
what is the Type 5 secretion system?
an auto transporter that transports itself across the outer membrane (the protein transports itself)
195
what is the makeup of the T5SS?
a large multi domain protein, including a Sec signal sequence, a beta domain, and other domains such as alpha, gamma, and sometimes a protease
196
the overall mechanism of T5SS?
protein is auto transported using the N-terminal signal sequence, entering the periplasm where it then travels through the beta domain of the T5SS and autocleaves it self into two parts (alpha and gamma), released from the outer membrane
197
what is the function of T1SS?
translocates protein directly from the cytoplasm to the cell surface, bypassing the Sec system and the periplasm
198
in what state are proteins translocated via the T1SS?
unfolded
199
what is the inner membrane component of the T1SS and what is its function?
an ATP binding cassette (ABC) transporter that serves as a channel in the cytoplasmic membrane. it supplies energy to the whole system
200
what is the signal sequence of T1SS?
C-terminal signal sequence consisting of a glycine-rich sequence repeated up to 36 times
201
what bacterial pathogen uses T1SS?
E. Coli - secretes alpha hemolysin
202
what is the outer membrane component of T1SS made up of?
a channel made of three monomers
203
what is the function of the Type 3 secretion system?
forms a channel through the bacterial cytoplasmic membrane, the periplasm, the outer membrane, and the host cell membrane so bacterial proteins can be injected into the host cell cytosol
204
what category of bacteria uses Type 3 secretion system?
a large number of gram-negative bacteria
205
what are T3SS effectors?
bacterial toxins transported by the T3SS - no B subunit because the specificity and transport is provided by the T3SS itself
206
what is the make-up of T3SS?
made of 3 channel complexes, one for each membrane it crosses. subunits must be transported in a chronological order: bacterial channel, needle, needle extension, translocation pore - effectors are then directly transported into the host cytoplasm
207
what bacterial pathogen uses T3SS?
Yersinia pestis - using this secretion system avoids the antibody-mediated immune response
208
what system is T3SS similar to?
the flagellar assembly system
209
what is the function of the T4SS?
translocates proteins and DNA in a contact-dependent and ATP-driven manner. very tight contact is needed
210
where is the T4SS sometimes found?
on PAI's
211
what is the make up of T4SS?
12 proteins that form a complex that span the 2 membranes of the bacteria. this system is related to the tra conjugal-transfer system used to transfer plasmid DNA
212
what bacterial pathogen largely uses T4SS?
L. pneumophila
213
what is the function of T6SS?
directly injects proteins into the host cells in a contact-dependent, ATP-driven mechanism. can also deliver toxins into other bacterial cells.
214
T6SS has a structural similarity with ...
bacteriophage tail proteins - may have originated from a defective prophage
215
what is the function of outer membrane vesicles?
eliminate toxic compounds and misfolded proteins. can also be used to transfer toxins into host cells via fusion of the OMV with the host cell.
216
what secretion systems are specific to gram-positive bacteria?
cytolysin-mediated translocation (CMT) (sec-dependent) and T7SS (sec-independent)
217
what is the main difference between sec systems in gram-positive and gram-negative bacteria?
sec systems in gram-positive bacteria do not involve a periplasm or an outer membrane because they do not exist in gram-pos.
218
what is the function of cytolysin-mediated translocation (CMT)?
secretes pore-forming toxins in to the host cytoplasm, creating a pore in the host membrane. this allows other bacterial proteins, such as toxins, to enter the host cells
219
an ____ binds to the host cell and ensures that the sec-system and the cytolysin are correctly aligned
adhesin
220
what is the T7SS particularly efficient for?
rapidly transporting bacterial toxins across the bacterial membrane and cell envelope of Mycobacterium and Gram positive
