Kachur - Topic 2 - Bacterial Structure Flashcards

1
Q

What is peptidoglycan?

A
  • repeating disaccharide of NAG and NAM
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2
Q

What is NAG

A
  • N-acetyl glucosamine
  • a monosaccharide derivative of glucose
  • amide between glucosamine and acetic acid
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3
Q

What is NAM

A
  • N-acetyl muramic acid
  • monosaccharide derivative of NAM
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4
Q

How are NAG and NAM cross-linked

A

with oligopeptides at the lactic acid residue of NAM

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5
Q

How do crosslinking peptides between gram positive and gram negative differ

A

Gram pos
- 9-15 aa
- often pentaglycine cross link
Gram neg
- 2 aa crosslink
- tetrapeptide links directly to another tetrapeptide

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6
Q

What is special about the D isomer of amino acids

A
  • uncommon in nature
  • used in bacteria to avoid protease digestion
  • key to regulating disease
  • connects through lysine component
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7
Q

What is N. gonorrhea?

A
  • gram negative
  • highly cross-linked -> harder to break down
  • resistant to some antibiotics
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8
Q

What is the lipopolysaccharide layer?

A
  • major component of the outer membrane of Gram negative bacteria
  • elicit strong immune responses (O antigen can induce strong immune responses)
  • LPS contribute greatly to the structural integrity of the bacteria and protecting the membrane from chemical attacks
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9
Q

How does LPS affect the charge of the cell membrane

A
  • LPS also increases the negative charge of the cell membrane and helps stabilize the overall membrane structure
  • LPS requires association with divalent cations (Mg++) to neutralize charge repulsion
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10
Q

What are the 3 molecular domains of LPS?

A
  • lipid A
  • the core
  • the O-antigen
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11
Q

What are the non-essential components of the LPS

A
  • the core and the O antigen
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12
Q

What is Lipid A?

A
  • phosphorylated glucosamine disaccharide with associated fatty acids
  • 4-6 fatty acids tails
  • allows bilayer formation
  • antigenic
  • bacteria can function with only Lipid A
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13
Q

What is the core?

A
  • attached directly to Lipid A
  • mostly sugar but can contain amino acids
  • diverse
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14
Q

What is Kdo?

A

the most common sugar in LPS

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15
Q

What is the O-antigen

A

attached to core olysaccharide
- highly diverse
- often determines strain type

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16
Q

What is the difference between rough and smooth LPS?

A
  • rough O antigen generally associate with non-pathogens (less variable, usually less resistant to antibiotics)
  • smooth can generally be more virulent than rough
  • long O antigens are associated with virulence
17
Q

What is the lipid A domain responsible for

A

toxicity of the gram negative bacteria
- upon bacterial lysis by the immune system, fragments containing lipid A are released into circulation causing:
- fever, diarrhea and endotoxic shock

18
Q

What are the different types of PAMPS

A
  • peptidoglycan
  • lipid A
  • teichoic acid
  • capsules
  • these are all unique to bacteria -> allow host detection
19
Q

What are toll-like receptors (TLRs)?

A
  • recognize PAMPs
  • expressed in all cells of innate immune system (either on cell surface or endosomes)
  • when a TLR is bound by a ligand, it activates a signalling cascade that initiates the release of pro-inflammatory cytokines
20
Q

What is TLR6?

A
  • recognizes peptidoglycan in gram +
  • recognizes lipoteichoic acid in gram +
  • recognize lipoproteins of gram -
21
Q

What is TLR4?

A
  • recognizes LPS in gram -
  • found on cell surface
22
Q

What is TLR3?

A
  • found in endosomes
  • detects intracellular + phagocytosed pathogens
23
Q

What are NODs

A
  • nucelotide-binding domain, leucine rich-repeat - containing receptors)
  • sensors of intracellular PAMPS
  • overlap between TLR cascades and NOD cascades
24
Q

What is the pathogen profile of helicobacter pylori?

A
  • gram negative
  • acid tolerant
  • infects lining of gut (asymptomatic)
  • cause acute gastritis + chronic inflammation (ulcers)
  • survives in the gut by secreting a base to neutralize acid + liquify mucus
  • flagellar bundle: spirochaete shape allows it to penetrate mucus layer
25
Q

What does NOD 1 recognize?

A

a modified dipeptide commonly found in gram negative

26
Q

What does NOD 2 recognize?

A

peptidoglycan in both gram + and gram -

27
Q

What is the pathogen profile of Listeria monocytogenes?

A
  • gram negative
  • causes listeriosis: serious infection usually caused by eating contaminated food
  • likely to sicken pregnant women and their newborns, adults aged 65 or older and people with weakened immune systems
  • can grow 0-37 degrees Celcius
  • present in soft cheeses + raw milk
  • attached to host via D-galactose (sugar on surface)
  • can survive in phagocytes + can manipulate host cytoskeleton
28
Q

How does Lm evade NLR recognition

A

50% of NAG replaced by glucosamine through deacetylation by the PgdA enzyme

29
Q

What are some modifications in the cell envelope that help Lm evade NLR recognition

A
  1. Deacetylation of NAG by PgdA
  2. Glycosylation of teichoic acid = mechanism that enhances virulence is unknown
  3. Lysine is added to cell walls to increase + charge
  4. Adaptation for virulence => enhancing + charges which allows avoidance of cationic AMPs
30
Q

Why are lipid A modifications important

A

essential to evade AMPs and TLR4

31
Q

What are evasion strategies of Helicobacter pylori that promote survival in the host

A
  1. Dephosphorylation = removes (-) charge, resistant to CAMPs
  2. Removal of (-) charge by adding amine
  3. 2 fewer HC tails: hexacylated lipid A is highly antigenic
32
Q

What are evasion strategies of Yersinia pestis that promote survival in the host

A
  • when residing in the flea vector, Y. pestis produces an endotoxic hexa-acylated lipid A that is a strong immunostimulant in humans
  • temperature change from fleas in humans causes changes in gene expression => turns on virulence genes
  • in fleas = hexacylated lipid A is antigenic but not to flea
  • Yersinia is virulent at 37 degrees
  • enzyme is activated with temp shift that cleaves 2 acyl chains = TLR4 evasive
33
Q

What are evasion strategies of Vibrio cholera

A

water borne illness that exists in copepod reservoirs
- addition of a diglycine to Lipid A decreases AMP sensitivity

34
Q

What are antimicrobial peptides?

A
  • potent members of the innate immune response
  • have been shown to kill gram-negative and gram-positive bacteria
35
Q

What are different subgroups of antimicrobial peptides?

A
  • alpha helices
  • beta sheets
  • mixture of alpha and beta
  • cyclic
  • extended
36
Q

What is Kalata B2?

A
  • found in plants
  • shown to have insecticidal, antitumor, antimicrobial
37
Q

What are the three models of action mechanisms by AMPs

A

A) Barrel-Stave model: AMP inserts perpendicularly
B) Carpet model: small areas of membrane are coated in AMPs
C) Torodial pore model: represents Barrel Stave except AMP associates with phospholipid head