Adherence Flashcards
(47 cards)
1
Q
what must a pathogenic microbe do to survive in a host and establish infection (5)
A
- attach to host cells for colonization
- evade host’s innate and adaptive immune defenses and persist
- obtain iron and other nutrients needed to multiply
- disseminate or spread within a host and to other hosts
- produce symptoms of disease (to be considered pathogenic)
2
Q
what is adherence mediated by (2)
A
- bacterial appendages or surface structures
- interactions can occur directly or indirectly
3
Q
adherence: direct interactions
A
- “adhesin” on bacterium binds directly to a specific receptor
4
Q
adherence: indirect interactions (2)
A
- adhesin binding first to the protein in the extracellular matrix (ECM)
- then, the ECM proteins binds to specific receptors on the host cell, acting as a bridge
4
Q
adherence: indirect interactions (2)
A
- adhesin binding first to the protein in the extracellular matrix (ECM)
- then, the ECM proteins binds to specific receptors on the host cell, acting as a bridge
5
Q
types of adhesins (2)
A
- fimbrial adhesins
- afimbrial adhesins
6
Q
fimbrial adhesins (3)
A
- fimbriae or pili
- several types that form polymers
- Pap pilus is heavily characterized and studied
7
Q
afimbrial adhesins (2)
A
- several types
- a single protein
8
Q
why do bacteria use long fragile structures to bind to host cells (3)
A
- outreach
- protection and survivability of core bacterial body from host immune system
- bacterial surface and host cell are negative; allows for connection despite repulsive forces
9
Q
can bacterium have multiple adhesins
A
- yes, they can be expressed all at once or sequentially during infection at different stages of pathogenesis
10
Q
are all adhesins virulence factors (2)
A
- as bacteria can have multiple adhesins, it is difficult to prove necessity of any one adhesin
- not all adhesins are virulence factors
11
Q
host receptors for adhesins (4)
A
- often carbohydrate-based
- glycolipids or glycoproteins
- often integrins
- receptors determine the tropism of the disease
12
Q
what is the receptor for Pap pilus (3)
A
- glycolipid
- a P-blood group antigen called gal (alpha1-4) gal
- found in the upper bladder and near the kidney (defining its tropism)
13
Q
what is the receptor for H. pylori (2)
A
- Lewis B-blood group antigen
- found in stomach epithelium
14
Q
tropism
A
- tissue specificity
15
Q
what binds to integrins
A
- ECM proteins or bacterial adhesins that contain RGD motif
16
Q
integrins (3)
A
- have 2 chains: alpha and beta chains
- have an extracellular and intracellular domain
- intracellular domain is involved in signaling
17
Q
what is the RGD motif (2)
A
- arginine, glycine, aspartic acid sequence
- often binds integrin
18
Q
integrin example
A
- CR3
19
Q
pathogenic E. coli (3)
A
- causes a variety of diseases
- all pathogenic E. coli express toxins and adhesins
- gram negative
20
Q
diseases caused by pathogenic E. coli (4)
A
- gastrointestinal
- invasive
- meningitis
- UTIs
21
Q
gastrointestinal pathogenic E. coli (2)
A
- watery diarrhea (cholera-type)
- bloody diarrhea (shigella-type)
22
Q
invasive pathogenic E. coli
A
- salmonella-type infection
23
Q
UTIs (2)
A
- 5-10% of people have a UTI in their life
- UTIs can be caused by variety of organisms, including E. coli
24
what are the host defenses in our urinary tract against UTIs (5)
- pH
- microbiota
- flushing
- metabolites
- osmolarity
25
pyelonephritis (3)
- caused by urinary pathogenic E. coli (UPEC)
- colonization of the gut or vagina serves as reservoir for organism
- bacteria then colonize the bladder and ascend to the kidneys
26
UPEC virulence factors (3)
- adhesins
- hemolysin (toxin that lyses RBCs and released iron)
- serum resistance proteins
27
how are UPEC virulence factors connected
- they are linked together on the chromosome; found in a gene cluster
28
Pap pilus assembly proteins (3)
- structural component proteins
- assembly proteins
- gene regulation proteins
29
Pap pilus gene regulation proteins (2)
- PapI
- PapB
30
Pap pilus structural components (6)
- PapA
- PapH
- PapE
- PapF
- PapG
- PapK
31
Pap pilus assembly proteins (2)
- PapD: chaperone
- PapC: usher
32
Pilus structure (6)
- PapG: binds to host
- PapF: adaptor protein
- PapE: multi-subunit
- PapK: adaptor
- PapA: multi-subunit
- PapH: interacts with outer membrane
33
PapG (3)
- the major adhesin
- found on the tip of the pilus as a single protein
- joined to PapE by PapF
34
PapF
- adaptor between PapG and PapE
35
PapE
- subunits make up the thin fibrillum
36
PapK
- adaptor between the thick pilus PapA rod and the PapE fibrillum
37
PapA
- polymer of repeating PapA subunits makes up a thick pilus rod
38
PapH (2)
- terminates assembly of the pilus
- links the rode to the outer membrane
39
Pilus assembly: PapD (2)
- assists in folding of subunits when they enter the periplasm
- properly folded subunits are founds as assembly modules
40
Pilus assembly: missing PapD (2)
- subunits will misfold and aggregate
- aggregation will lead to degradation
41
donor strand complementation (3)
- C-terminus of the subunits have alternating hydrophobic residues
- subunits line up in register with a similar region in PapD
- two beta strands (one from subunit and one from chaperone) are found in parallel conformation
42
Pilus assembly: PapC (3)
- assembly site for the pilus
- where donor strand exchange (DSE) occurs
- directs the ordered assembly of the subunits by influence of relative affinities of subunits and abundance of subunits
43
donor strand exchange (4)
- at PapC, the PapD chaperone is released, allowing the subunits to polymerize
- one strand from the subunit and one strand from another subunit are now found in anti-parallel conformation
- this new interaction is very strong as it has high affinity
- interaction occurs via the N-terminus of the incoming subunit
44
donor strand complementation vs exchange (2)
- chaperone/subunit interactions are "loose"
- subunit/subunit interactions are stable and tight; strand snap into place
45
affinities and order for PapC (3)
- PapD + PapG has highest affinity for PapC, so it binds first
- PapD + PapF assembly module is next, and so on
- PapH finds and anchors the pilus as it lacks the region that initiates DSE
46
what is a strategy to produce soluble PapG
- genetically link donor strand from chaperone to PapG to prevent PapG from misfolding and degrading
