Gram-Negative Bacterial Structure and Endotoxin in Human Diseases Flashcards
Another name for group A strep is _
Streptococcus pyogenes
What is petechia? In the context of case 3, what is thought to cause it?
Petechia are small red spots (blood clots)
Endodoxin
What is the mechanism by which endotoxin causes its damage?
It causes clotting in the capillaries, causing adjacent tissues to die and blood to leak into the tissues
There are 6 microbes that cause meningitis. What are the 2 that cause meningitis in people of all ages?
Streptococcus pneumoniae (all ages) Neisseria meningitidis (all ages)
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?
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
There are 6 microbes that cause meningitis. What are the 3 major causes in neonates? Which 2 combine for 80% of cases?
Streptococcus agalactiae (40%) Escherichia coli (40%) listeria monocytogenes
What is another name for group B strep?
Streptococcus agalactiae
In the context of case 3, what was the cause of the patient’s meningitis?
Neisseria menigiditis
In the context of case 3, what were the reasons (3) that neisseria meningiditis was thought to cause the patient’s disease?
– Extremely severe and rapidly progressing illness
– Purpura fulminans
– Cultures ultimately grew Neisseria meningitidis capsule group C
Another name for purpura fulminans is _
Waterhouse-Friderichsen Syndrome)
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?
A, B, C, Y and W135
B not included because its capsule is not immunogenic
What is the antibiotic treatment used to treat Neisseria meningiditis?
Cephalosporin (A beta lactam)
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?
Gram negative
Diplococcus
Encapsulated
Kidney bean shaped cocci
In case 3, what was regarded as the ultimate cause of death?
Fulminant meningococcemia
Fulminant - rapid onset
meningococcemia - meningococci in the blood
Neisseria meningiditis has a capsule. What is its significance for the organism? How does it attach to the host?
Capsule in antiphagocytic, it doesn’t allow proper deposition of antibodies that lead to complement cascade
Neisseria meningiditis attaches by pili
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?
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
How is Neisseria meningiditis spread? Of the various capsule groups that cause disease, which is considered sporadic?
Intimate contact
Capsule B
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?
True
False - Petechia can become purpura fulminans, which can progress to necrosis if untreated
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?
Lipotechoic acid - anchors
Techoic acid - within murein sac components
Gram + dont have outer membranes
How is the peptidoglycan layer similar and different between gram + and gram -?
Similar - same components
Different - Less cross linked
What are the 2 layers found outside the peptidoglycan layer of the gram - organism? Together, these form the _
Phospholipid layer
Lipopolysaccharide layer
Outer membrane of gram -
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?
The periplasm is what is between the 2 membranes
Large molecules (above 800 MW)
Outside the outer layer
How is the periplasm related to toxicity in e. coli?
In ecoli, the toxins produced are bigger than 800 MW, therefore they are trapped there until cell division, when they are released
What are the 2 components of the periplasmic space in the gram negative bacteria?
Lipoprotein and think peptidoglycan wall
What are 2 other names for endotoxin? What is its significance? What antibodies can protect against endotoxin?
Endotoxin AKA LPS AKA O-antigen
It is the immunogenic component of gram negative bacteria
Antibodies are not protective against LPS
What are the 2 examples of outer membrane proteins of gram negative bacteria provided? What are their functions?
Porins - Trimers that transport molecules
Secretion systems - Transport virulence factors
How are outer membrane proteins held in the outer membrane (2)?
Either embedded in the membrane or …
Covalently linked to peptidoglycan
What are the 2 functions of pili in gram negative bacteria?
Attachment to host
Attachment to related bacteria
What happens when you treat a gram negative bacteria with EDTA and lysozyme? Can this event be reversed?
You create a spheroplast - A cell wall deficient bacteria
If the whole cell wall is not removed, the cell wall can regenerate
What are the 3 components of LPS?
O side chain sugars
Core polysaccharide
Lipid A
What is the function of the O side chain in LPS? Is it immunogenic? Is it toxic?
It gives antigentic specificity
Immunogenic but not toxic
What is the significance of the core polysaccharide? What are 2 examples of unusual sugars contained within?
Shared by all Enterobacteriaceae
Heptose and KDO (ketodeoxyoctonate)
What is the significance of lipid A? What is the main chemical component? What is the major type of bond linking these components?
It is the toxic part of the LPS
N acetyl glucosamine
Phosphodiester bonds
What is the significance of the phosphodiester bond in LPS? What is monophosphoryl Lipid A?
It is what confers toxicity
Mono-Lipid A is not toxic but it is immunogenic
If you find ketodeoxyoctonate (KDO) anywhere, what does that tell you? What are the major components of all gram negative core proteins?
It tells you that the area has been contaminated by gram negative bacteria
KDO and heptose
What is the difference between bacteremia and septicemia?
Bacteremia - bacteria in blood, no symptoms
Septicemia - bacteria in blood, with symptoms (e.g fever and hypotension) despite fluid resusitation
True or false, only gram negative bacteria can cause septic shock.
False - both gram pos and neg can, but gram neg is better
What is the main cause of multiorgan dysfunction syndrome?
The host’s immune system
LPS and LOS differ because of _. An example of an organism with LOS is _. Which is more toxic?
Incomplete O side chain in LPS
Neisseria has LOS
Both just as toxic
What is the difference between endotoxin and exotoxin?
Endotoxin - Part of gram negative cell wall
Exotoxin - Any secreted toxin from gram negative or gram positive
How does exotoxin secretion differ in gram positive an negative organisms?
Secreted out into surroundings in gram positive, or into periplasm and or surrounding in gram negative
Which is more lethal, exotoxin or endotoxin?
Exotoxin (lethal in ng to pg range)
Endotoxin (lethal in microgram range)
Which is more likely to be enzymatic, exotoxin or endotoxin?
Endotoxin is non-enzymatic whereas many exotoxins are
enzymatic
Which is more likely to be a genetic trait, exotoxin or endotoxin?
Exotoxin can be acquired
Endotoxin is a component of viable gram negative bacteria
What is an enterotoxin?
An exotoxin that acts in the GI tract
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
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)
What are the 2 types of Toll Like receptors bound by LTA? What is the 1 type of TLR bound by LPS?
LTA - TLR 2 or 6
LPS - TLR 4
Upon binding TLR 2/4/6, what are the cytokines that will cause fever? What are the cytokines that will cause hypotension?
Fever - IL-1beta, IL-6
Hypotension - TNF-alpha
What is a specific symptom that is associated with infection by superantigen? What are the associated cytokines? What cytokine causes superantigen hypotension?
Rash
INF-gamma and IL2
TNF-beta
What are the 2 types of cells that superantigen crosslinks to get its response? What are the binding targets?
Cross links APC (macrophage or CD4) with T-cells
Binds MHC II (alpha or beta chain) with the alpha AND beta chain of TCR
What is the specific molecule on T cells that TSST-1 recognizes? How does this molecule’s expression change from basal to infected state?
Recognizes the V-beta2 molecule
Basal 10% of cells, infection, now on 70% of cells
What are the 3 superantigens that were provided as examples?
TSST-1
Staph enterotoxin
Strep scarlet fever toxin
