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micb 308 > Adherence > Flashcards

Adherence Flashcards

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)
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2
Q

what is adherence mediated by (2)

A
  • bacterial appendages or surface structures
  • interactions can occur directly or indirectly
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3
Q

adherence: direct interactions

A
  • “adhesin” on bacterium binds directly to a specific receptor
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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
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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
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5
Q

types of adhesins (2)

A
  • fimbrial adhesins
  • afimbrial adhesins
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6
Q

fimbrial adhesins (3)

A
  • fimbriae or pili
  • several types that form polymers
  • Pap pilus is heavily characterized and studied
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7
Q

afimbrial adhesins (2)

A
  • several types
  • a single protein
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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
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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
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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
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11
Q

host receptors for adhesins (4)

A
  • often carbohydrate-based
  • glycolipids or glycoproteins
  • often integrins
  • receptors determine the tropism of the disease
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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)
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13
Q

what is the receptor for H. pylori (2)

A
  • Lewis B-blood group antigen
  • found in stomach epithelium
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14
Q

tropism

A
  • tissue specificity
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15
Q

what binds to integrins

A
  • ECM proteins or bacterial adhesins that contain RGD motif
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16
Q

integrins (3)

A
  • have 2 chains: alpha and beta chains
  • have an extracellular and intracellular domain
  • intracellular domain is involved in signaling
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17
Q

what is the RGD motif (2)

A
  • arginine, glycine, aspartic acid sequence
  • often binds integrin
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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
Q

what are the host defenses in our urinary tract against UTIs (5)

A
  • pH
  • microbiota
  • flushing
  • metabolites
  • osmolarity
25
Q

pyelonephritis (3)

A
  • 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
Q

UPEC virulence factors (3)

A
  • adhesins
  • hemolysin (toxin that lyses RBCs and released iron)
  • serum resistance proteins
27
Q

how are UPEC virulence factors connected

A
  • they are linked together on the chromosome; found in a gene cluster
28
Q

Pap pilus assembly proteins (3)

A
  • structural component proteins
  • assembly proteins
  • gene regulation proteins
29
Q

Pap pilus gene regulation proteins (2)

A
  • PapI
  • PapB
30
Q

Pap pilus structural components (6)

A
  • PapA
  • PapH
  • PapE
  • PapF
  • PapG
  • PapK
31
Q

Pap pilus assembly proteins (2)

A
  • PapD: chaperone
  • PapC: usher
32
Q

Pilus structure (6)

A
  • PapG: binds to host
  • PapF: adaptor protein
  • PapE: multi-subunit
  • PapK: adaptor
  • PapA: multi-subunit
  • PapH: interacts with outer membrane
33
Q

PapG (3)

A
  • the major adhesin
  • found on the tip of the pilus as a single protein
  • joined to PapE by PapF
34
Q

PapF

A
  • adaptor between PapG and PapE
35
Q

PapE

A
  • subunits make up the thin fibrillum
36
Q

PapK

A
  • adaptor between the thick pilus PapA rod and the PapE fibrillum
37
Q

PapA

A
  • polymer of repeating PapA subunits makes up a thick pilus rod
38
Q

PapH (2)

A
  • terminates assembly of the pilus
  • links the rode to the outer membrane
39
Q

Pilus assembly: PapD (2)

A
  • assists in folding of subunits when they enter the periplasm
  • properly folded subunits are founds as assembly modules
40
Q

Pilus assembly: missing PapD (2)

A
  • subunits will misfold and aggregate
  • aggregation will lead to degradation
41
Q

donor strand complementation (3)

A
  • 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
Q

Pilus assembly: PapC (3)

A
  • 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
Q

donor strand exchange (4)

A
  • 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
Q

donor strand complementation vs exchange (2)

A
  • chaperone/subunit interactions are “loose”
  • subunit/subunit interactions are stable and tight; strand snap into place
45
Q

affinities and order for PapC (3)

A
  • 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
Q

what is a strategy to produce soluble PapG

A
  • genetically link donor strand from chaperone to PapG to prevent PapG from misfolding and degrading

micb 308 (22 decks)

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