Term
| Microbial Content within the Host |
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Definition
-About a 1:1 ratio of 30 trillion human cells to 30 trillion bacteria cells
-Colon and teeth have richest proportion
of bacterial cells
5000-10000 different bacterial species
-Most variety found in skin and intestines |
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Term
| The Three main surfaces (substrata) of Microbial Attachment to the Host |
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Definition
• skin
• mucosae
• teeth
Bacteria must be flexible in attachment due to range of surfaces
--> Streptococci and staphylococci attach to a lot of different body parts |
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Term
| The Three Steps of Colonization of Host Cell Surfaces |
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Definition
1. Non-specific interactions (first, weak entrance)
− Hydrophobic interactions
− Cation-bridging
2. Initial anchoring adhesion (weak, smapling surface)
– Pili, S-layer, capsule, flagella
3. Tight adhesion (receptor-ligand interaction)
– Specific adhesins |
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Term
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Definition
• Hydrophobic interactions:
– non-polar molecules on bacterial surface/host
• Cation-bridging:
– Divalent metal ions (eg. Ca2+)
- Bridges with + ions as the cell surfaces are typically negative |
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Term
| Bacterial Adherence Mechanisms |
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Definition
• Pili/fimbriae:
– mediate initial attachment
• S-layers
• Capsules
• Flagella:
– Motility/attachment
• Adhesins:
– intimate attachment between bacterial/host |
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Term
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Definition
• Pilus:
– ordered array of single pilin subunits (20 kDa)
• Tip of pilus attaches to molecule on host surface
– glycoproteins or glycolipids – specialized tip structure
• Vary phenotypically – different tip
• Expression can be turned on and off
“Phase Variation” - Helps with tissue tropism (can stop expression, release and go elsewhere) |
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Term
| Pap (pyelonephritis-associated pili) pili: |
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Definition
– uropathogenic E. coli (UPEC) strains
– binds to glycolipids on host cells lining upper urinary tract
-Pili binds high number of mannose on
the tract (opposite of the norm)
-Ascending Urinary tract infection
-Gram negative |
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Term
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Definition
– binds to mannose-containing host molecules
(Mannose within host, exception to generally high
mannose seen on pathogens and not host)
– all E. coli strains, including UPEC
-Gram (-) |
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Term
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Definition
– enteropathogenic E. coli, Vibrio cholerae, Neisseria spp.
– Bind to gangliosides (carbohydrates) on host
-gram (-) |
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Term
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Definition
– Thin, aggregative pili
– diarrhea-producing E. coli strains, Salmonella enteritidis
– Bind to fibronectin, laminin, plasminogen
-Gram (-) |
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Term
| Tissue tropism and pili expression |
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Definition
• Uropathogenic E. coli – Pap pili and Type I pili– bladder cells
• Enteropathogenic E. coli – Type IV pili – intestinal cells |
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Term
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Definition
| (Type I pili) binds mannosylated glycoproteins - bladder |
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Term
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Definition
| binds gala1-4galb disaccharides - kidney cell glycosphingolipids |
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Term
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Definition
Flagellum as an Adhesin
Pseudomonas aeruginosa
– FliD mediates attachment to mucin (sticky stuff on top of mucosal layer)
-FliD is the Pili tip structure |
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Term
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Definition
• Mediate tight adherence
• Most pathogens possess many adhesins
• Differentially regulated
Regulation depends on which stage in infection
-Adhesives turned on closer to infection
• Often multifunctional |
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Term
| Attachment of adhesin to host cell (effects) |
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Definition
– Signal transduction within the bacterium
-Secretion systems infect into host following attachment
-Via typeIII (at least in E. coli)
– Uptake of the bacterium by the host cell = invasion
– Signaling within the host cell |
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Term
| Pseudomonas aeruginosa Adhesion |
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Definition
Type IV Pili - Flagella and FliD Adhesin
Attachment induces Type III secretion system
Effector proteins
• ExoS and ExoT
• ExoU and ExoY
ExoU: Cleaves phospholipids within plasma membrane within host cell resulting in cell death |
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Term
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Definition
-Killing/impairment of phagocytes
-Disruption of epithelial/endothelial barriers |
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Term
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Definition
Down regulation of IL-1beta and IL-18
-Will dampen inflammatory response
-Pseudomonas aeruginosa lung infections typically lead to other infections of the lung due to this weakening |
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Term
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Definition
N. gonorrhoeae and N. meningitidis
• Pili
• Opa Adhesins
-Deep invasion allows infection to exist for long and systemic infection |
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Term
| Neisseria Pili (Type IV) - Initial Attachment |
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Definition
PilE – pilin protein
N-terminus of protein – conserved (function)
C-terminus of protein – hypervariable (invasion) |
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Term
| Opa (Opacity) Adhesins - Result in Tight Adherence |
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Definition
• Family of outer membrane proteins found in N. gonorrhoeae and N. meningitidis
• Mediate adherence to epithelial cells, endothelial cells, T lymphocytes, neutrophils |
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Term
| Host Cell Receptors that Opa Attaches To |
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Definition
– Vitronectin, heparin sulfate proteoglycans
– CEACAM family (carcinoembryonic antigen cell adhesion molecule) |
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Term
| Neutrophil Opa-CEACAM engagement |
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Definition
Bacteria taken in and killed
-Thought to be decoy mechanism |
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Term
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Definition
Movement of bacteria deeper into tissues and through cells
-ex. Neisseria: there is attachment to the epithelial layer --> movement through this layer via transcytosis (from OPA and CEACAM engagement at points) --> moves into deeper epithelial layer --> moves through endothelial layer --> can enter blood stream and deseminate through, spreading infection |
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Term
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Definition
Invasion of host cells by intracellular pathogens
Tissue invasion by pathogens
– Extracellular pathogens
-> gain access to deeper tissue by going through cell junction
-used by many extracellular pathogens |
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Term
| Facultative Intracellular Bacteria Examples |
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Definition
-Salmonella spp. (typhoid, gastroenteritis)
-Yersinia spp. (plague, gastroenteritis)
-Listeria monocytogenes (listeriosis) |
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Term
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Definition
-E. coli (gastroenteritis, meningitis)
-Streptococcus pyogenes (fasciitis, rheumatic fever) |
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Term
| Overview of Tissue Organization |
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Definition
– Cell junctions
– Extracellular matrix (ECM)
Connective and Epithelia tissue |
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Term
| General Characteristics of Connective Tissue |
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Definition
-cells sparse
-ECM plentiful
-cell-cell attachment rare
-matrix bears stress |
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Term
| General Characteristics of Epithelial Tissue |
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Definition
-cells plentiful
-ECM sparse
-cell-cell junctions prevalent
-cells bear stress
-epithelial layer is tightly packed
with not a lot of extracellular
tissues; no cushioning |
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Term
| Three Types of Cell Junctions |
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Definition
1. Occluding
2. Anchoring
3. Communicating -Gap junctions
found in every cell and tissue
-important for communication, relay electrical impulses and signals, prevalent in places like retina, muscles, etc
-open exchange between cells
-only allows small cells to pass between them (<1000Da)
-signals allow for response to occur within a tissue |
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Term
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Definition
Tight Junctions
• Seal cells together in epithelium
• Selective permeability barriers
• Prevent nutrients from diffusing back into lumen
• Keep transport proteins and things in place |
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Term
| Occluding Junction Receptors |
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Definition
Apical receptors = faces lumen
Basolateral receptors = face bloodstream |
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Term
| How Occluding Junctions Hold Together |
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Definition
-Formed from: claudin and occludins membrane proteins
-link with cytoskeletal proteins |
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Term
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Definition
Anchors via cell-cell and cell-matrix
Mediate cell-cell and cell-matrix junctions
-important for survival
-without this interaction, cells will die |
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Term
| Transmembrane adhesion proteins |
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Definition
Adherens junctions and desmosomes
•cell-cell junctions
•cadherin family
Focal adhesions and hemidesmosomes
•cell-matrix junctions
•integrin family |
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Term
| Intracellular anchor proteins interactions |
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Definition
Adherens junctions and focal adhesions:
-talin and vinculin
-interact with actin filaments
Desmosomes and hemidesmosomes:
-plectin
-interact with intermediate filaments |
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Term
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Definition
Function:
• mediate cell-ECM attachment
• matrix-cell and cell-matrix signaling
-important for survival through contact with matrix, development of cell layers and structure of cell layers |
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Term
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Definition
Structure
• a and b subunits (alpha and beta)
-9 b subunits
-24 a subunits
•overlapping recognition
-8 integrins bind fibronectin
-5 integrins bind laminin
Pathogens can mimic these components to allow invasion |
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Term
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Definition
The RGD Region is the cell-binding motif
--> aa's R,G,D ; binds integrin molecules
Pathogens exploit the RGD motif |
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Term
| Pathogen Exploitation of Anchoring Junctions (E-Cadherin) |
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Definition
Pathogen protein binds to cell-cell anchoring junction protein
– binds to E-cadherin
-internalin binds e cadherin (cell-cell)
– Eg. Yersinia pseudotuberculosis invasin -binds b1 integrins
Listeria monocytogenes internalin - binds E-cadherin |
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Term
| Mechanisms used by bacteria to enter cells: INVASION |
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Definition
Trigger
-massive disruption and reorganization
-membrane ruffling
Zipper
-not a lot of disruption; invagination, pathogen comes in
Opa: binds CEACAM, IntA/A (internalin), Invasin (InvA) etc |
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Term
| Salmonella invasion - SopB |
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Definition
-induces membrane ruffling
-activates Rho kinase-dependent actin rearrangement recruits AnnexinA2
-induces actin rearrangement |
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Term
| Salmonella invasion - SopE/E2 |
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Definition
-guanine nucleotide exchange factors
-activates Rho GTPases
induces actin polymerization and membrane ruffling |
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Term
| Salmonella invasion - SipA/SipC |
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Definition
-bind to actin
-inhibits actin depolymerization (SipA)
-nucleates actin (SipC) |
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Term
| Salmonella invasion - SptP |
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Definition
-induces actin depolymerization
-Does this by removal of inorganic P group
--> Inactive GDP |
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Term
| Salmonella invasion - SipB/C (Before SopB) |
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Definition
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Term
| Invasive Extracellular Pathogens |
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Definition
Generally, their goal is not to get within a cell; they want to stay extracellular
virulence factors allows them to stay extracellular and combat immune response
-BUT they do want to get deeper into tissues |
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Term
| Mechanisms of Invasion for Extracellular Pathogens |
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Definition
1. Exploitation of anchoring junctions
– Transcytosis: allows access to deeper epithelium and bloodstream -->also allows access to the lymphatic system
-Just like Firbronectin yersinia example
2. Disruption of tight junctions
Then they will spread via the bloodstream |
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Term
| Pathogen exploitation of tight junctions |
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Definition
Enteropathogenic E. coli (EPEC) – disrupts tight junctions
-causes diarrhea (related to tight junction disruption) |
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Term
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Definition
• Binds to: Actin, nWASP, Arp2/3
• Causes:
– Actin removal from Tight Junction (TJ)
– Recruitment of TJ proteins into pedestal
• EspF mutant:
– No TJ disruption
- Smaller pedestals
(EspF till needs other effector proteins to work) |
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Term
| What Happens in EspF Mutant? |
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Definition
An EspF mutant (does not express EspF) causes formation of smaller pedestals. THIS IS BECAUSE:
-you still get pedestal formation because of Tir, but EspF is needed to get extra movement into the pedestals (ZO proteins wouldn't move) |
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