Gram-Negative Bacterial Structure and Endotoxin in Human Diseases

Question 1

Another name for group A strep is _

Answer 1

Streptococcus pyogenes

Question 2

What is petechia? In the context of case 3, what is thought to cause it?

Answer 2

Petechia are small red spots (blood clots)

Endodoxin

Question 3

What is the mechanism by which endotoxin causes its damage?

Answer 3

It causes clotting in the capillaries, causing adjacent tissues to die and blood to leak into the tissues

Question 4

There are 6 microbes that cause meningitis. What are the 2 that cause meningitis in people of all ages?

Answer 4

Streptococcus pneumoniae (all ages)
Neisseria meningitidis (all ages)

Question 5

There are 6 microbes that cause meningitis. What is the one that causes it in individuals 3 months to 7 years, but is not uncommon due to vaccines? What is the target of the vaccine? What is the significance of 3 months?

Answer 5

Haemophilus influenzae type b
Vaccine targets the capsule of the microbe
3 months is usually when neonates run out of maternal antibodies, and the accompanying protection

Question 6

There are 6 microbes that cause meningitis. What are the 3 major causes in neonates? Which 2 combine for 80% of cases?

Answer 6

Streptococcus agalactiae (40%)
Escherichia coli (40%)
listeria monocytogenes

Question 7

What is another name for group B strep?

Answer 7

Streptococcus agalactiae

Question 8

In the context of case 3, what was the cause of the patient’s meningitis?

Answer 8

Neisseria menigiditis

Question 9

In the context of case 3, what were the reasons (3) that neisseria meningiditis was thought to cause the patient’s disease?

Answer 9

– Extremely severe and rapidly progressing illness
– Purpura fulminans
– Cultures ultimately grew Neisseria meningitidis capsule group C

Question 10

Another name for purpura fulminans is _

Answer 10

Waterhouse-Friderichsen Syndrome)

Question 11

There are 5 major capsule groups of Neisseria meningiditis that the most common causes of meningitis. What are they? Which is not included in the vaccine and why?

Answer 11

A, B, C, Y and W135

B not included because its capsule is not immunogenic

Question 12

What is the antibiotic treatment used to treat Neisseria meningiditis?

Answer 12

Cephalosporin (A beta lactam)

Question 13

Neisseria meningiditis is gram positive or negative? Is it a rod, spirochete, coccus, diplococcous, or other? Encapsulated or not? What defining characteristic would it have under a microscope?

Answer 13

Gram negative
Diplococcus
Encapsulated
Kidney bean shaped cocci

Question 14

In case 3, what was regarded as the ultimate cause of death?

Answer 14

Fulminant meningococcemia
Fulminant - rapid onset
meningococcemia - meningococci in the blood

Question 15

Neisseria meningiditis has a capsule. What is its significance for the organism? How does it attach to the host?

Answer 15

Capsule in antiphagocytic, it doesn’t allow proper deposition of antibodies that lead to complement cascade
Neisseria meningiditis attaches by pili

Question 16

In case 3, all the student were vaccinated for Neisseria meningiditis, including the meningitis group C capsule that infected the patient. Why was this ineffective? What is the new protocol now for a potential Neisseria meningiditis outbreak? Why is this better?

Answer 16

Because the production of IgM antibodies takes 4 days, too slow to help the patient.
Treatment of exposed people with Rifampin
Rifampin penetrates mucosal barriers very well

Question 17

How is Neisseria meningiditis spread? Of the various capsule groups that cause disease, which is considered sporadic?

Answer 17

Intimate contact

Capsule B

Question 18

True or false, in the brain, Neisseria meningiditis can lead to pus formation?
True or false, petechia and purpura fulminans are unrelated, and only purpura fulminans can lead to necrosis?

Answer 18

True

False - Petechia can become purpura fulminans, which can progress to necrosis if untreated

Question 19

Gram positive cell walls are composed of _ and _. Which remains within the cell wall and which anchors to the PM below? What anchors to the outer membrane?

Answer 19

Lipotechoic acid - anchors
Techoic acid - within murein sac components
Gram + dont have outer membranes

Question 20

How is the peptidoglycan layer similar and different between gram + and gram -?

Answer 20

Similar - same components

Different - Less cross linked

Question 21

What are the 2 layers found outside the peptidoglycan layer of the gram - organism? Together, these form the _

Answer 21

Phospholipid layer
Lipopolysaccharide layer
Outer membrane of gram -

Question 22

What is the periplasm? What types of products may be trapped within the periplasm? Where would the capsule be found in a gram negative organism?

Answer 22

The periplasm is what is between the 2 membranes
Large molecules (above 800 MW)
Outside the outer layer

Question 23

How is the periplasm related to toxicity in e. coli?

Answer 23

In ecoli, the toxins produced are bigger than 800 MW, therefore they are trapped there until cell division, when they are released

Question 24

What are the 2 components of the periplasmic space in the gram negative bacteria?

Answer 24

Lipoprotein and think peptidoglycan wall

Question 25

What are 2 other names for endotoxin? What is its significance? What antibodies can protect against endotoxin?

Answer 25

Endotoxin AKA LPS AKA O-antigen It is the immunogenic component of gram negative bacteria Antibodies are not protective against LPS

Question 26

What are the 2 examples of outer membrane proteins of gram negative bacteria provided? What are their functions?

Answer 26

Porins - Trimers that transport molecules | Secretion systems - Transport virulence factors

Question 27

How are outer membrane proteins held in the outer membrane (2)?

Answer 27

Either embedded in the membrane or ... | Covalently linked to peptidoglycan

Question 28

What are the 2 functions of pili in gram negative bacteria?

Answer 28

Attachment to host | Attachment to related bacteria

Question 29

What happens when you treat a gram negative bacteria with EDTA and lysozyme? Can this event be reversed?

Answer 29

You create a spheroplast - A cell wall deficient bacteria | If the whole cell wall is not removed, the cell wall can regenerate

Question 30

What are the 3 components of LPS?

Answer 30

O side chain sugars Core polysaccharide Lipid A

Question 31

What is the function of the O side chain in LPS? Is it immunogenic? Is it toxic?

Answer 31

It gives antigentic specificity | Immunogenic but not toxic

Question 32

What is the significance of the core polysaccharide? What are 2 examples of unusual sugars contained within?

Answer 32

Shared by all Enterobacteriaceae | Heptose and KDO (ketodeoxyoctonate)

Question 33

What is the significance of lipid A? What is the main chemical component? What is the major type of bond linking these components?

Answer 33

It is the toxic part of the LPS N acetyl glucosamine Phosphodiester bonds

Question 34

What is the significance of the phosphodiester bond in LPS? What is monophosphoryl Lipid A?

Answer 34

It is what confers toxicity | Mono-Lipid A is not toxic but it is immunogenic

Question 35

If you find ketodeoxyoctonate (KDO) anywhere, what does that tell you? What are the major components of all gram negative core proteins?

Answer 35

It tells you that the area has been contaminated by gram negative bacteria KDO and heptose

Question 36

What is the difference between bacteremia and septicemia?

Answer 36

Bacteremia - bacteria in blood, no symptoms | Septicemia - bacteria in blood, with symptoms (e.g fever and hypotension) despite fluid resusitation

Question 37

True or false, only gram negative bacteria can cause septic shock.

Answer 37

False - both gram pos and neg can, but gram neg is better

Question 38

What is the main cause of multiorgan dysfunction syndrome?

Answer 38

The host's immune system

Question 39

LPS and LOS differ because of _. An example of an organism with LOS is _. Which is more toxic?

Answer 39

Incomplete O side chain in LPS Neisseria has LOS Both just as toxic

Question 40

What is the difference between endotoxin and exotoxin?

Answer 40

Endotoxin - Part of gram negative cell wall | Exotoxin - Any secreted toxin from gram negative or gram positive

Question 41

How does exotoxin secretion differ in gram positive an negative organisms?

Answer 41

Secreted out into surroundings in gram positive, or into periplasm and or surrounding in gram negative

Question 42

Which is more lethal, exotoxin or endotoxin?

Answer 42

Exotoxin (lethal in ng to pg range) | Endotoxin (lethal in microgram range)

Question 43

Which is more likely to be enzymatic, exotoxin or endotoxin?

Answer 43

Endotoxin is non-enzymatic whereas many exotoxins are | enzymatic

Question 44

Which is more likely to be a genetic trait, exotoxin or endotoxin?

Answer 44

Exotoxin can be acquired | Endotoxin is a component of viable gram negative bacteria

Question 45

What is an enterotoxin?

Answer 45

An exotoxin that acts in the GI tract

Question 46

How will a gram negative cause shock? About how much toxin needed? How will a gram positive cause chock? About how much toxin needed? What about super antigen

Answer 46

``` Gram neg., LPS about 1 microgram per human Gram positive, LTA / peptidoglycan, about 1 millgram per human Super entigent (e,g, TSS, only 0.1 microgram per human needed) ```

Question 47

What are the 2 types of Toll Like receptors bound by LTA? What is the 1 type of TLR bound by LPS?

Answer 47

LTA - TLR 2 or 6 | LPS - TLR 4

Question 48

Upon binding TLR 2/4/6, what are the cytokines that will cause fever? What are the cytokines that will cause hypotension?

Answer 48

Fever - IL-1beta, IL-6 | Hypotension - TNF-alpha

Question 49

What is a specific symptom that is associated with infection by superantigen? What are the associated cytokines? What cytokine causes superantigen hypotension?

Answer 49

Rash INF-gamma and IL2 TNF-beta

Question 50

What are the 2 types of cells that superantigen crosslinks to get its response? What are the binding targets?

Answer 50

Cross links APC (macrophage or CD4) with T-cells | Binds MHC II (alpha or beta chain) with the alpha AND beta chain of TCR

Question 51

What is the specific molecule on T cells that TSST-1 recognizes? How does this molecule's expression change from basal to infected state?

Answer 51

Recognizes the V-beta2 molecule | Basal 10% of cells, infection, now on 70% of cells

Question 52

What are the 3 superantigens that were provided as examples?

Answer 52

TSST-1 Staph enterotoxin Strep scarlet fever toxin