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Cameron Feb 20-23
Flashcards
53
Microbiology
Undergraduate 4
03/13/2017

Additional Microbiology Flashcards

 


 

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Term
Microbial Content within the Host
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
Term
The Three main surfaces (substrata) of Microbial Attachment to the Host
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
Term
The Three Steps of Colonization of Host Cell Surfaces
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
Term
Non-Specific Interations
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
Term
Bacterial Adherence Mechanisms
Definition
• Pili/fimbriae:
– mediate initial attachment
• S-layers
• Capsules
• Flagella:
– Motility/attachment
• Adhesins:
– intimate attachment between bacterial/host
Term
Pili (General Features)
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)
Term
Pap (pyelonephritis-associated pili) pili:
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
Term
Type I pili
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 (-)
Term
Type IV pili
Definition
– enteropathogenic E. coli, Vibrio cholerae, Neisseria spp.
– Bind to gangliosides (carbohydrates) on host
-gram (-)
Term
Curli Pili
Definition
– Thin, aggregative pili
– diarrhea-producing E. coli strains, Salmonella enteritidis
– Bind to fibronectin, laminin, plasminogen
-Gram (-)
Term
Tissue tropism and pili expression
Definition
• Uropathogenic E. coli – Pap pili and Type I pili– bladder cells

• Enteropathogenic E. coli – Type IV pili – intestinal cells
Term
FimH
Definition
(Type I pili) binds mannosylated glycoproteins - bladder
Term
PapG
Definition
binds gala1-4galb disaccharides - kidney cell glycosphingolipids
Term
FliD
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
Term
Adhesins
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
Term
Attachment of adhesin to host cell (effects)
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
Term
Pseudomonas aeruginosa Adhesion
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
Term
ExoS, T, U
Definition
-Killing/impairment of phagocytes
-Disruption of epithelial/endothelial barriers
Term
ExoS and ExoU
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
Term
Neisseria sp
Definition
N. gonorrhoeae and N. meningitidis
• Pili
• Opa Adhesins
-Deep invasion allows infection to exist for long and systemic infection
Term
Neisseria Pili (Type IV) - Initial Attachment
Definition
PilE – pilin protein
N-terminus of protein – conserved (function)
C-terminus of protein – hypervariable (invasion)
Term
Opa (Opacity) Adhesins - Result in Tight Adherence
Definition
• Family of outer membrane proteins found in N. gonorrhoeae and N. meningitidis

• Mediate adherence to epithelial cells, endothelial cells, T lymphocytes, neutrophils
Term
Host Cell Receptors that Opa Attaches To
Definition
– Vitronectin, heparin sulfate proteoglycans

– CEACAM family (carcinoembryonic antigen cell adhesion molecule)
Term
Neutrophil Opa-CEACAM engagement
Definition
Bacteria taken in and killed
-Thought to be decoy mechanism
Term
Transcytosis
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
Term
Invasive Pathogen
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
Term
Facultative Intracellular Bacteria Examples
Definition
-Salmonella spp. (typhoid, gastroenteritis)
-Yersinia spp. (plague, gastroenteritis)
-Listeria monocytogenes (listeriosis)
Term
Extracellular bacteria
Definition
-E. coli (gastroenteritis, meningitis)
-Streptococcus pyogenes (fasciitis, rheumatic fever)
Term
Overview of Tissue Organization
Definition
– Cell junctions
– Extracellular matrix (ECM)

Connective and Epithelia tissue
Term
General Characteristics of Connective Tissue
Definition
-cells sparse
-ECM plentiful
-cell-cell attachment rare
-matrix bears stress
Term
General Characteristics of Epithelial Tissue
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
Term
Three Types of Cell Junctions
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
Term
Occluding Junctions
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
Term
Occluding Junction Receptors
Definition
Apical receptors = faces lumen

Basolateral receptors = face bloodstream
Term
How Occluding Junctions Hold Together
Definition
-Formed from: claudin and occludins membrane proteins
-link with cytoskeletal proteins
Term
Anchoring Junctions
Definition
Anchors via cell-cell and cell-matrix

Mediate cell-cell and cell-matrix junctions
-important for survival
-without this interaction, cells will die
Term
Transmembrane adhesion proteins
Definition
Adherens junctions and desmosomes
•cell-cell junctions
•cadherin family

Focal adhesions and hemidesmosomes
•cell-matrix junctions
•integrin family
Term
Intracellular anchor proteins interactions
Definition
Adherens junctions and focal adhesions:
-talin and vinculin
-interact with actin filaments

Desmosomes and hemidesmosomes:
-plectin
-interact with intermediate filaments
Term
Integrins (Function)
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
Term
Integrins (Structure)
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
Term
Fibronectin
Definition
The RGD Region is the cell-binding motif
--> aa's R,G,D ; binds integrin molecules

Pathogens exploit the RGD motif
Term
Pathogen Exploitation of Anchoring Junctions (E-Cadherin)
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
Term
Mechanisms used by bacteria to enter cells: INVASION
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
Term
Salmonella invasion - SopB
Definition
-induces membrane ruffling
-activates Rho kinase-dependent actin rearrangement recruits AnnexinA2
-induces actin rearrangement
Term
Salmonella invasion - SopE/E2
Definition
-guanine nucleotide exchange factors
-activates Rho GTPases
induces actin polymerization and membrane ruffling
Term
Salmonella invasion - SipA/SipC
Definition
-bind to actin
-inhibits actin depolymerization (SipA)
-nucleates actin (SipC)
Term
Salmonella invasion - SptP
Definition
-induces actin depolymerization
-Does this by removal of inorganic P group
--> Inactive GDP
Term
Salmonella invasion - SipB/C (Before SopB)
Definition
T3SS pore
Term
Invasive Extracellular Pathogens
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
Term
Mechanisms of Invasion for Extracellular Pathogens
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
Term
Pathogen exploitation of tight junctions
Definition
Enteropathogenic E. coli (EPEC) – disrupts tight junctions
-causes diarrhea (related to tight junction disruption)
Term
EspF - Effector Protein
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)
Term
What Happens in EspF Mutant?
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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