19 - Bacterial Invasion Flashcards
1
Q
Use of term “invasiveness”
A
- Ability of a microbe to enter a host, grow and reproduce within the host and spread throughout the body
- Entry and survival within phagocytic cells
- Ability to enter non-phagocytic host cells, such as epithelial cells
2
Q
Ability of a microbe to enter a host, grow and reproduce within the host and spread throughout the body
A
Mediated by production of lytic substances or “spreading factors” that may alter or damage host tissue
3
Q
Collagenase
A
- Breaks down collagen
- E.g. Clostridium
4
Q
Fibrinolysin
A
- Digests fibrin clots
- e.g. Staphylococcus
5
Q
Hyaluronidase
A
- Depolymerises hyaluronic acid
- e.g. Streptococcus
6
Q
DNase
A
- Destroys DNA
- E.g. Clostridium, Staphylococcus, Streptococcus
7
Q
Three niches in phagocyte that intracellular pathogen survive by exploiting
A
- Bacteria live in phagolysosome and are resistant to killing
- Bacteria live in the phagosome and prevent phagosome-lysosome fusion
- Bacteria escape from phagosome into cell cytoplasm
8
Q
Ability to enter non-phagocytic host cells, such as epithelial cells
A
- Results in bacterial colonisation within the mucosa,
- or bacterial translocation across the mucosal barrier,
- or bacterial access to deeper or systemic tissues by way blood or lymphatic vesicles
9
Q
How do bacteria force “non professional phagocytes” to take them up
A
- Bacteria attach to host cell surface
- Cause changes to host cell cytoskeleton, causing actin rearrangements and pseudopod formation
10
Q
Invasins
A
Bacterial surface proteins that provoke uptake
11
Q
How does invasion benefit the bacterial pathogen
A
- Provides a safe environment for bacterial growth
- Gain nutrients from host
- No competition for nutrients from other microbes
- Pathogen can evade host immune system and antibiotics
12
Q
Two main mechanisms for invasion of non phagocytic cells
A
- Zipper mechanism
- Trigger mechanism
13
Q
Zipper mechanism
A
- Bacterial invasins bind to host cell receptors at a number of points along the cells
- Actin polymerization is triggered and bacteria are surrounded by tight-fitting pseudopodia and engulfed into phagosome
14
Q
Trigger mechanism
A
- Bacteria inject molecules into host cell via Type III secretion apparatus
- These activate changes to host cell’s actin cytoskeleton causing membrane ruffles or “splash”, leading to uptake of bacterial cell by host cell
15
Q
Examples of bacteria that use zipper mechanism
A
Listeria and Yersinia
16
Q
Examples of bacteria that use trigger mechanism
A
Shigella and Salmonella
17
Q
T3SS in trigger mechanism
A
- Type 3 needle is embedded in bacterial cell envelope
- Close physical contact between bacterial and eukaryotic cell
- Proteins travel from bacterial cell through hollow needle into eukaryotic cell (injection)
- Trigger membrane ruffling
18
Q
Listeria
A
- Gram positive rods
- Causes serious food-borne infections (listeriosis)
- Facultative intracellular pathogen
- Invades wide variety of cells including phagocytes, liver cells, epithelial cells
19
Q
Pathogenic species of listeria
A
Listeria monocytogenes
20
Q
Listeria zipper mechanism
A
- Listeria InLB (internalin, an invasin) binds to the host cell Met receptor
- Binding triggers a signal transduction that activates ARP 2/3 complex
- These promote the recruitment of G actin and assembly of F-actin to result in bacterial uptake by the host cell
21
Q
Cell to cell spread of listeria after invasion by zipper mechanism
A
- Bacteria contained within vesicle
- Bacteria lyse vacuole membrane and escape into cytoplasm
- Bacteria polymerise actin filaments at one end of cell forming actin tails which propel them through cytoplasm
- Bacteria push into neighbouring cells, forming a protrusion which buds off forming a double membrane vacuole in the new cell
- Bacteria lyse vacuole and enter new cell’s cytoplasm
22
Q
Actin based motility “comet tails”
A
- Actin is one of the proteins that makes up the eukaryotic cell cytoskeleton
- Listeria cells are able to induce the polymerisation of actin monomers into polymers at one end of the bacterial cell (mediated by Listeria’s ActA protein which activates host cell’s ARP2/3)
- Long actin tails form, where actin is being depolymerised at the end of the tail while being polymerised at the bacterial surface
- This provides a force to push the bacteria through the cell cytoplasm
23
Q
Shigella
A
- Gram negative rods
- Causes bacillary dysentery (bloody diarrhoea)
- Invades cells of the colon
24
Q
Invasion by trigger mechanism of Shigella
A
- Shigella are taken up by M cells in colon
- Reach the resident macrophages and are endocytosed
- Escape from the phagosome and induce death of macrophage
- Shigella are released from macrophage
- Enter epithelial cell from basolateral surface (underneath) by inducing actin polymerisation and engulfment
25
Cell to cell spread of Shigella
1. Shigella enter cell in vacuole, lyse the vacuole membrane, and escape into cell cytoplasm and multiply
2. Move rapidly within cytoplasm via actin mediated motility (lack flagella)
26
Cell to cell spread of Shigella
- Same as Listeria
- Lack flagella
27
Salmonella
- Gram negative rods
- Invade cells of small intestine via T3SS
- Salmonella enterica serovar Typhi causes typhoid fever
- Other serovars cause enterocolitis/diarrhoea
- Bacteria are ingested from contaminated water or animal products
28
Invasion by trigger mechanism and spread of salmonella
- Invade cells of small intestine via T3SS
- Vacuoles then translocate across cell using two host microtubule proteins
- Bacteria are released to underlying tissues, and then phagocytosed, survive and disseminate systemically
29
Salmonella vs shigella
- Following invasion from the lumen, Salmonella are translocated across intestinal epithelium and gain access to host circulation
- After translocation, Salmonella survive within phagocytes by preventing phagosome-lysosome fusion
- Bacteria disseminate to systemic sites
30
IpaB
- Adhesion
- Binds CD44 receptor
- Located at needle tip, supported by IpaD scaffold proteins
31
IpaC
Travels up needle, interacts with IpaB and inserts into host cell membrane forming a pore
32
IpaA
Actin depolymerisation
33
Invasion mechanism of listeria, shigella and salmonella
- Listeria: Zipper (invasions)
- Shigella: Trigger (T3SS)
- Salmonella: Trigger (T3SS)
34
Internal spread of listeria, shigella and salmonella
- Listeria: Actin based motility
- Shigella: Actin based motility
- Salmonella: Survival and spread in phagocytes
35
IpaC, IpgB1, IpgB2 and lpgD
Actin polymerisation
36
IpaB and D
IpaB located at needle tip, supported by IpaD scaffold proteins, forming needle tip complex
