Bacterial Structure

Question 1

What does peptidoglycan consist of?

Answer 1

A repeating disaccharide of NAG and NAM

Question 2

What is NAG?

Answer 2

A monosaccharide derivative of glucose
An amide between glucosamine and acetic acid

Question 3

What is NAM?

Answer 3

A monosaccharide derivative of NAM (ether of lactic acid and NAM)

Question 4

What are NAG and NAM cross-linked with?

Answer 4

Oligopeptides at the lactic acid residue of NAM

Question 5

How do cross-linking peptides differ between Gram-negative and Gram-positive bacteria?

Answer 5

MAIN DIFFERENCE: Gram-positive links tetrapeptides with a pentaglycine crosslink and Gram-negative tetrapeptides link directly to other tetrapeptides

Gram-positive = 9-13 aa long
Gram-negative = 8 aa long

Question 6

What is unique about D isomers and why do bacteria use them in their PG?

Answer 6

They are uncommon in nature and are used by bacteria to avoid protease digestion

Question 7

Why does gonorrhea have some resistance to antibiotics?

Answer 7

Because they have highly cross-linked PG layers

Question 8

What is the LPS a major component of and what does it do?

Answer 8

The outer membrane of Gram-negative bacteria
It is important for the structural integrity of the bacteria and protects the membrane from chemical attack

Question 9

What does the LPS do to the charge of the cell membrane and why does it do that?

Answer 9

It increases the negative charge
Helps stabilize the overall membrane structure

Question 10

What does LPS associate with and why?

Answer 10

Divalent cations (Mg++) to neutralize charge repulsion

Question 11

What are the 3 molecular domains of LPS?

Answer 11

Lipid A
The core
The O-antigen

Question 12

What is the structure of Lipid A and what does it allow?

Answer 12

Phosphorylated glucosamine disaccharide with associated fatty acids
The fatty acids allow bilayer formation and it is antigenic

Question 13

What is the core made up of and what does it attach to?

Answer 13

The core is made up of mostly sugars (can contain amino acids) and it attaches directly to lipid A
Diverse

Question 14

What is the O-antigen attached to and what does it determine?

Answer 14

It is attached to the core oligosaccharide and due to it being highly diverse, it often determines strain type

Question 15

What are the implications of O-antigen being presented on the cell surface?

Answer 15

It is antigenic and therefore the bacteria are always changing it

Question 16

What are long O-antigens associated with?

Answer 16

Virulence

Question 17

What does smooth O-antigens make?

Answer 17

A gel and it appears smooth

Question 18

What are rough O-antigens associated with?

Answer 18

Non-pathogens

Question 19

What part of lipid A anchors the LPS into the bacterial membrane? Where is the rest of the LPS?

Answer 19

The hydrophobic fatty acid chains anchor LPS into the cell membrane
The rest of the LPS projects from the cell surface

Question 20

What is the lipid A domain responsible for?

Answer 20

The toxicity of Gram-negative bacteria

Question 21

When bacterial cells are lysed, what does the release of lipid A into circulation cause?

Answer 21

Fever
Diarrhea
Endotoxic shock (sepsis)

Question 22

What types of bacterial PAMPs can PRRs detect?

Answer 22

PG
Lipid A
Teichoic acid (links layers of Gram-positive PG)
Capsules

Question 23

What do TLRs do and where are they expressed?

Answer 23

They recognize PAMPs
They are expressed in all cells of the innate immune system and can be found on the cell surface or inside endosomes

Question 24

Where are endosomes located?

Answer 24

In between the plasma membrane and Golgi

Question 25

What does TLR6 recognize?

Answer 25

PG in Gram-positive Lipoteichoic acid in Gram-positive Lipoproteins of Gram-negative

Question 26

What does TLR4 recognize?

Answer 26

LPS in Gram-negative + LPS with co-receptor MD2

Question 27

What does TLR3 recognize and where is it found?

Answer 27

Detects intracellular and phagocytized pathogens Found in endosomes

Question 28

What are NODs and what do they detect?

Answer 28

Nucleotide-binding domain, Leucine-rich repeat-containing receptors They detect intracellular PAMPs

Question 29

Why is there often an overlap between TLRs and NODs?

Answer 29

They can detect the same pathogen

Question 30

Where is H. pylori found, what is unique about it, and what does it cause?

Answer 30

It infects the gut lining It is acid tolerant It can cause acute gastritis and chronic inflammation

Question 31

How does H. pylori survive in the gut?

Answer 31

It secretes a base to neutralize the acid and liquifies mucous Its flagellar bundle and spirochaete shape allows it to penetrate the mucous layer

Question 32

Which NODs recognize H. pylori?

Answer 32

NOD-1 and NOD-2

Question 33

What does NOD-2 recognize?

Answer 33

PG from both Gram-positive and Gram-negative

Question 34

What does NOD-1 recognize?

Answer 34

A modified dipeptide commonly found in Gram-negative (mDAP)

Question 35

What is the cause of listeriosis and who is most susceptible?

Answer 35

Eating contaminated food Pregnant women, infants, old people, and the immunocompromised

Question 36

What foods should pregnant women avoid to not get listeria?

Answer 36

Soft cheese and raw milk

Question 37

What temperature can Listeria survive at and what type of pathogen is it?

Answer 37

0°C-37°C Opportunistic

Question 38

How does listeria attach to a host and what can it survive?

Answer 38

Attaches to the host via D-galactose (sugar on surface) Can survive phagocytes and manipulate host cytoskeleton

Question 39

What is unique about the peptidoglycan of listeria?

Answer 39

50% of NAG is replaced with glucosamine by the PgdA enzyme which is a virulence factor so that the host cannot recognize it

Question 40

What does deacetylation of listeria PG allow the evasion of?

Answer 40

NOD-1

Question 41

What are 3 ways that listeria evades NLRs?

Answer 41

Deacetylation of NAG by PgdA Glycosylation of teichoic acid = enhances virulence Lysine is added to cell walls to increase the positive charge

Question 42

What is the purpose of adapting to enhance positive charges?

Answer 42

Normally bacteria are negatively charged By enhancing positive charges, it allows the avoidance of CAMPs

Question 43

What is Kdo2-lipid A?

Answer 43

The most common sugar in core oligosaccharides

Question 44

What are the enzymes to modify Kdo?

Answer 44

periplasmic

Question 45

What are modifications of Kdo2-lipid A essential to avoid?

Answer 45

AMP TLR4

Question 46

How does Y. pestis modify Kdo2-lipid A?

Answer 46

Glycosylation to PO4-

Question 47

How does H. Pylori modify Kdo2-lipid A?

Answer 47

Only has 4 acyl chains Masking of a negative charge on PO4-

Question 48

How does P. aeruginosa modify Kdo2-lipid A?

Answer 48

Glycosylation of PO4- to shield negative charges from AMP

Question 49

How does V. cholerae modify Kdo2-lipid A?

Answer 49

Addition of PO4 Addition of acyl chains

Question 50

What are the 3 lipid A evasion strategies that H. pylori uses?

Answer 50

1. dephosphorylation = lose PO4- to remove negative charge which adds resistant to CAMPs 2. Removal of the negative charge by adding an amine 3. Fewer HC tails as hexacylated lipid A is very antigenic

Question 51

What does the temperature change from fleas to humans cause in Y. pestis?

Answer 51

Causes a change in gene expression which turns on virulent genes

Question 52

What does Y. pestis look like in fleas?

Answer 52

Has a hexacylated lipid A but is not antigenic to the flea

Question 53

What does Y. pestis do in humans?

Answer 53

An enzyme is activated with the temperature shift that cleaves 2 acyl chains which makes it TLR4 evasive

Question 54

At which temperatures is Y. pestis virulent and non-virulent?

Answer 54

Virulent = 37°C Non-virulent = 25°C

Question 55

What evasion strategies on lipid A does V. cholera use?

Answer 55

Addition of a diglycine to lipid A which decreases AMP sensitivity

Question 56

What type of illness is cholera?

Answer 56

Water-borne illness that exists in copepod reserviors

Question 57

What are AMPs and what can they kill?

Answer 57

Nonspecific components of the immune response, like to punch holes Can kill Gram-negative and Gram-positive bacteria `

Question 58

What are the subgroups of AMPs?

Answer 58

Alpha-helices Beta-sheets Mixed alpha/beta Cyclic Extended

Question 59

Where might alpha-helix AMPs be found?

Answer 59

In the lysosome of macrophages

Question 60

What is Kalata B2?

Answer 60

Found in plants and has been shown to have insecticidal, anti-tumor, and antimicrobial functions CAMPs that detect negative surface charges

Question 61

How do AMPs kill bacteria?

Answer 61

By making pores

Question 62

What are defensins?

Answer 62

Short peptides with an positive charge and a lot of hydrophobic residues that allows it to adopt amphipathic structures in membrane-mimicking enviornments

Question 63

Where is a high concentration of defensins found and what might they aid in?

Answer 63

Breast milk Colonization of the gut

Question 64

How do Gram-positive bacteria resist defensins?

Answer 64

Modification to cell wall teichoic acid to decrease negative charge Add positively charged membrane proteins to offset negative charge

Question 65

How do Gram-negative bacteria resist defensins?

Answer 65

Modification to LPS = more acyl chains = harder for AMP to penetrate Secrete negatively charged proteins which act as decoys for CAMPS

Question 66

What is the last line of resistance to defensins?

Answer 66

Efflux pumps = pump out the AMPs Proteases = destroy AMP

Question 67

What is molecular mimicry?

Answer 67

Structural, functional, or immunological similarities shared between macromolecules found on pathogens and in host tissues

Question 68

What can molecular mimicry induce?

Answer 68

Autoimmune responses which attack and destroy body tissues or organs

Question 69

What is Guillain-Barre's syndrome?

Answer 69

An infection with Campylobacter that causes autoimmune disease temporary

Question 70

How does C. jejuni showcase molecular mimicry?

Answer 70

The LPS of C. jejuni has evolved molecular similarity to GH1 gangliosides in human neurons