Structure - LPS

Question 1

Lipopolysaccharides

Answer 1

A constituent of gram-negative bacteria membrane, providing integrity.

Question 2

What are the three poritons of LPS?

Answer 2

Lipid A
Core Oligosaccharide
O Antigen

Question 3

What is the function of Lipid A?

Answer 3

Anchors LPS to the membrane
Acts as an Endotoxin

Question 4

What is the structure of Lipid A?

Answer 4

Two glucosamine residues linked by beta 1-6 glycosidic bonds with variable acyl chains.

Question 5

What is an example of Lipid A alteration?

Answer 5

Phosphorylation of glucosamine alters charge/solubility.

Question 6

How does Lipid A act as an endotoxin?

Answer 6

TLR4 pathway being a macrophage/DC expressed receptor

Question 7

What does Lipid A interaction with TLR4 result in?

Answer 7

Signalling cascades and TF activation like NF-kb resulting in cytokine stimulation of inflammation.

Question 8

What is an example of acyl chain variability?

Answer 8

Long chain C18 or C20 fa increases hydrophobicity and decreases solubility thus more prone to aggregation.

Question 9

Why do longer Acyl chains have lower affinity for TLR?

Answer 9

Less stability between Lipid A and TLR4

Question 10

What is the function of the Core Oligosaccharide?

Answer 10

Structural integrity LPS and a recognition site.

Question 11

What is the structure of the Core Oligosaccharide?

Answer 11

Anchors Lipid A by 3-deoxy-D-manno-octulosonic acid with three structural regions( inner and outer core and terminal reigon)

Question 12

Structure of CO inner core?

Answer 12

Heptose residue, 2-3 Kdo residues and N-Acetylcglucosamine

Question 13

Structure of CO outer core

Answer 13

Terminated by galactose, glucose or NAG, bound by the terminal region

Question 14

What is the function of the O-antigen Polysaccharide?An

Answer 14

Antigenic component
Host immune defense
Virulence Factor

Question 15

What is the structure of the O Antigen?

Answer 15

Several dozen sugar residues

Question 16

How does the O-antigen assist host infilitration?

Answer 16

Prevent recognition and binding of LPS like TLR

Question 17

Virulence Factor

Answer 17

Bacteria associated molecules required for bacteria to cause disease whilst infection eukaryotic host.

Question 18

What makes LPS amphiphatic?

Answer 18

Hydrophobic Lipid A and hydrophilic O-antigen and CO

Question 19

What determines LPS effects on membrane packing?

Answer 19

Length and saturation of the acyl chains.

Question 20

What happens when Lipid A binds TLR4?

Answer 20

Dimerisation bringing it into contact with cytoplasmic domains of two TLR, inducing downstream signalling pathways.

Question 21

Anaphylatic Shock

Answer 21

This is an acute allergic reaction with airway and circulatory problems.

Question 22

What is the most diverse component of LPS?

Answer 22

O Antigen.

Question 23

What is the primary function of the LPS?

Answer 23

Establishes a permeabilit barrier, protecting cell from entry of toxic molecules.

Question 24

Pathogenicity

Answer 24

The property of causing disease.

Question 25

What makes LPS a strong barrier?

Answer 25

Its amphiphatic nature, and its ability to pack densely together.

Question 26

What type of FA are Lipd A acyl portions?

Answer 26

Saturated FA.

Question 27

How is condensing of LPS complicated?

Answer 27

Repulsion of the negatively charged phosphate groups.

Question 28

How do LPS counter the negative repulsion of the phosphate groups?

Answer 28

Divalent cations like Mg which intercalate between LPS, forming interactions that enhance packing and promote barrier function.

Question 29

What makes LPS an endotoxin?

Answer 29

Its prevalence on surface of bacteria, thus host immune systems respond dramatically to it.

Question 30

What is an example of Lipid A structural diversity in relation to stimulation of TLR4?

Answer 30

Hexacylated, biphosphorylated Lipid A produced by E.Coli and Salmonella are highly immunogenic, whilst others are less so.

Question 31

Immunogenic

Answer 31

Substances that can produce an immune response.

Question 32

What are the ways GNB increase Lipid A diversity?

Answer 32

Covalent modifciations leading to changes in FA length, number of phosphates and carbohydrate moieties.

Question 33

How might bacteria evade host immune response, with respect to Lipid A?

Answer 33

Production of less immunogenic Lipid A.

Question 34

How does Yersinia Pestis modulate Lipid A response to TLR4?

Answer 34

Modulates acylation of LA at mammalian body temp, producing less immunogenic Lipid A.

Question 35

How does temperature regulate Yersinia Pestis acylation?

Answer 35

At 37 degrees, Lipid A is tetraacylated, with weaker stimulation, but at lower temperatures, its hexacylated with increased stimulation.

Question 36

What is the PagL gene?

Answer 36

A modifcation gene encoding Lipid A 3-0-deacylase in the outer mmebrane, modulation lipid A signalling.

Question 37

Kdo moieties

Answer 37

3-Deoxy-D-Manno-2-octulosonic acid, a key cell wall component.