3 Gram-Negative Bacterial Structure & Endotoxin in Human Diseases

Question 1

What symptoms would Schlievert’s story of a boy with Neisseria meningitidis gram-negative shock have?

Answer 1

VERY low B.P. (blood pressure), petechia (red spots), 24 hrs of nausea, vomiting, stiff neck, fever

[exteremely severe and rapid, can also have Purpura Fulminans]

Question 2

What’s petechia?

Answer 2

tiny red spots (minor hemorrhage) that is often associated with increased pressure/trauma or even clotting disorders.

Question 3

What are the 3 common causes of meningitis in non-babies

Answer 3

• Streptococcus pneumoniae (all ages)
• Neisseria meningitidis (all ages)
• Haemophilus influenzae type b (3 mo. to 7 yrs)

[1st 2 are the majority of cases]

Question 4

What are the 3 common causes of meningitis in neonates?

Answer 4

• Streptococcus aggalactiae (group B) [40%]
• Escherichia coli [40%]
• Listeria monocytogenes [10%]

Question 5

Which capsule groups of Neisseria meningitidis are common in the U.S.? Which one is not immunogenic?

Answer 5

• A, B, C, Y, W135

- B (no vaccine)

Question 6

How is gram-neg. shock due to N. Meningitidis treated?

Answer 6

• “Supportive therapy” (fluid & electrolytes for B.P., blood pressure)
• Coricosteroids prevent inflammation
• 3rd generation cephalosporin

Question 7

Describe the look a Neisseria meningitidis bacteria? (2 things)

Answer 7

encapsulated diplococcus

Question 8

What characteristics are important for N. meningitidis damage to host and virulence? (3)

Answer 8

• Encapsulated
• Gram-neg. (endotoxin)
• Antiphagocytic capsule

Question 9

Which antibiotic is for prophylactic treatment of N. meningitids? Why?

Answer 9

Rifampin. Penetrates mucosal membranes where n. meningitidis lives

Question 10

How is N. meningitids transmitted?

Answer 10

saliva, intimate contact more commonly than just a cough

Question 11

T/F n. meningitids causes pus around the meninges of the CNS?

Answer 11

T.

Question 12

In what 4 ways are gram negative cell walls different than gram positives?

Answer 12

• Thinner, less cross-linked (25 vs 75%) peptidoglycan layer
• Outer membrane (Phospholipid) atop peptidoglycan.
• LPS layer atop outer membrane.
• Periplasm zone between inner and outer membranes(includes the peptidoglycan layer)

Question 13

What are 4 key gram-negative structures?

Answer 13

• Outer Membrane Proteins (OMP’s)
• Pili
• Spheroplasts
• Flagella

Question 14

Porins are an example of what? What is the structure of a porin?

Answer 14

OMP’s (porins are trimers)

Question 15

Pili are made of? Have what function?

Answer 15

• Pilin

- sex w/ bacteria & attachment to host

Question 16

T/F All OMP’s are immunogenic, since they are proteins.

Answer 16

F.

Question 17

OMP’s attach to what part of the cell wall?

Answer 17

covalent link to peptidoglycan layer!

[NOT to outer layer of cell like you might think]

Question 18

What is the structure of LPS (lipopolysaccharide A)?

Answer 18

• O side chain sugars
• Core polysaccharide
• Lipid A

Question 19

Enterobacteriaceae share what common feature?

Answer 19

Core polysaccharide of LPS

Question 20

How is LPS identified in lab med?

Answer 20

Find KDO (ketodeoxyoctonate) sugar (or heptose)

Question 21

What is the toxic part of endotoxin (a.k.a. LPS)?

Answer 21

Lipid A

Question 22

What provide the antigen specificity of LPS?

Answer 22

O antigen.

Question 23

“emia” (suffix) means?

Answer 23

in the blood

Question 24

What is the cause of multiorgan dysfunction syndrome?

Answer 24

host immune response

Question 25

How are LPS and LOS different?

Answer 25

-Incomplete O side chain in the LPS means it is LOS.

[Our key example is Neisseria]

Question 26

T/F gram negative bacteria have exotoxin?

Answer 26

T, some do.

[Note: when secreted, if large it gets caught in the periplasm before reaching host]

Question 27

T/F the toxic portion of endotoxin is part of the gram negative cell wall facing the host?

Answer 27

F. (faces inside of the bacteria)

Question 28

T/F gram pos. bacteria have exotoxin?

Answer 28

T, some do.

Question 29

T/F endotoxin & exotoxin are enzymatic?

Answer 29

F, many exotoxins are but not endotoxin.

Question 30

Put in order of most to least potent: LTA-peptidoglycan(lipotechoic acid), superantigen exotoxin, LPS? What type of bacteria secretes each?

Answer 30

• Superantigen exotoxin (.1 ug) [Toxic shock syndrome bacteria types]
• LPS (1 ug) [gram neg]
• LTA-peptigoglycan (1 mg) [gram pos]

Question 31

enterotoxins are?

Answer 31

exotoxins that act on the enteron (gut)

[NOT endotoxins!]

Question 32

Exotoxins are made of what molecule type?

Answer 32

protein

[unlike LPS a lipid]

Question 33

Which type of bacterial toxin are variable traits genetically?

Answer 33

exotoxins.

[endotoxin doesn’t vary]

Question 34

Describe the immune cascade activated by LTA:

Answer 34

Macrophage
TLR2/6 ->
IL-1B, IL-6, (both=fever) , TNF-alpha=hypotension

Question 35

Describe the immune cascade activated by LPS?

Answer 35

Macrophage
TLR-4 ->
IL-1B, IL-6, (both=fever) , TNF-alpha=hypotension

Question 36

Describe the immune cascade activated by superantigen?

Answer 36

Macrophage presents to T-cell & gets crosslinked especially to Beta chain of TCR ->
Macrophage releases: IL-1B, IL-6, TNF-alpha
AND
T-cell releases: IFNgamma & IL-2 (rash) + TNF-Beta (hypotension)