bacillary dysentry (severe bloody and muscous diarhea; have no adherence factors.
In the colon and rectum Shigella_________ thru epithelial barrier via __ cells invading resident macrophages, escape from the phagosomes into cytoplasm, where they multiply and induce rapid cell death.
translocate , M cells
Released 4rm dead macrophages _______than infect other epithelial cells using a "trigger mechanism of entry."
When Shigella come into contact with epithelial cells, the ______________________ is stimulated & delivers effectors (IcsB) into host cells which play roles in camouflage against phagocytic recognition.
Type 2 Secretion system (TTSS)
What delivers effectors (IcsB) into the host cells ?
Type 2 secretion system (TTSS)
Bacterial toxins is some of the well known virulence factors on the ________ .
What is the mode of action/targets of toxins? (3)
protein synthesis stopped
cell wall integrity affected
nerve impulses interrupted
C. botulinum toxin is produced when....?
in food prior to ingestion.
bacteria form spores, pass thru GI tract and don't colonize GI tract / enter tissue.
toxin attacks neuron causing paralysis and death (collapse of respiratory system)
What is the natural source of C. botulinum?
What are 2 bacterias that do not have toxin genes that are part of their normal components of the bacterial genome?
C. botulinum (C&D) & Corynebacterium diphtheriae
(carried on lysogenic bacteriophage / plasmids)
Where are the toxin genes in C. botulinum and Corynebacterium diphtheriae?
lysogenic bacteriophage / plasmids
What is exotoxin ?
accumulated and released toxins on cell lysis.
injected directly into host cells therefore bypassing extracellular phase.
What are the 7 criterias for the naming system ?
1. cytotoxins: can have a more general action & attack a variety of cell types.
Endotoxin-structure of Gram (-) cell wall, recognized by immune sys (LPS)
Enterotoxin specific for toxins in small intestine producing diarrhea/vomiting ex: enteric symptoms
What are example pathogens that cause food poisoning ?
Sty. aureus, C. perfringens, B. cereus, Camp. jejuni
What are example of intestinal pathogens?
Vibrio cholera, E. coli, Salmonella enteritidis
Campylobacter jejuni is now the leading cause of ... ?
bacterial food poisoning, most often spread by contact with raw/undercooked poultry.
symptoms: diarrhea(bloody), fever(typical fever), ab pain, cramping, nausea, vomit
What is the 1st step in action of toxins?
binding to target cells
What are Type I Toxins?
What do Type I Superantigens bind to?
host surface but not translocated into cell.
ex: Superantigens bind to marcophages & T-cells and stimulate large amt of toxic cytokines.
Over-secretion of cytokines can trigger a dangerous syndrome known as a ... ?
Cytokine storm deaths were weighted more heavily towards people with _________ due to its ability to produce stronger immune responses, like increasing cytokine levels.
healthy immune systems
-nausea, vomit, malasie, and fever
Staphylococcus aureus (enterotoxin) and Streptococcal infections
Type II toxins are... ?
cytolytic / membrane disrupting
What are the 2 types of Type II toxins?
1. Proteins that form channels in membrane
2. Enzymes that disrupt the membrane phospholipid
What are 3 examples of proteins that form channels in the membrane ?
Streptococcal Streptolysin O
-affects sterols of host cytoplasmic membrane
-disrupt smooth muscle in blood vessels but also toxic to many cell types
What is a convenient test for testing toxins (ex: phospholipase, hemolysin, cytotoxin)?
blood agar assay
What cleaves at other sites to destabilize the cell membrane?
Enzymes that disrupt membrane phospholipid (2nd type of type II toxins) rather than make "holes" some enzymes just _________________ group of lipid portion of molecule that normally acts to stabilize lipid bilayer of cytoplasmic membrane -cell lysis.
remove charged head group
What toxin can enter bloodstream and damage kidneys?
C. perfringens α-toxin
Type III toxins (A-B) are... ?
protein inhibitor toxins
Type iii toxins (A-B) protein inhibitor toxins consist of 2 components...?
Active (enzymatic) (A) and Binding (B) portions
When does proteolytic cleavage occur ?
when the A portion is internalized and activated when disulphide bonds are broken.
Which portion of Type III toxin is more specific? A or B?
(B) portion is very specific [binds to carbohydrate moiety of a host cell glycoprotein/ glycolipid]
(A) portion = less specific and can kill several types of cell if it can gain entry into cytoplasm
What happens in Type III toxins when binding (B) occurs?
leads to A being translocated thru host membrane into cytoplasm .
What results in A becoming active and exerts its toxic effect?
endocytosis / direct translocation
Although diff cells may be attacked, the mode of action of toxin is the same... what is the mode of action ?
How does Scalded Skin Syndrome begin?
w/ a fever and redness of skin, followed by formation of fluid-filled blister that ruptures easily. Eventually, top layer of skin may peel off in sheets
What does Dipheria toxin do?
acts on elongation factor-2; normally brings an amino charged tRNA to ribosome -- prevents protein synthesis
What does Cholera-toxin (Enterotoxin) do?
ADP- ribosylates an enzyme that controls AMP and ion flow leading to massive water loss (diarrhea)
What occurs in Shiga toxin ?
(A) subunit cleaves a host cell rRNA molecule, which prevents ribosome carrying out translocation of proteins.
-protein synthesis is terminated
Endotoxins (nonprotein toxins) consists of what ? What are they a part of?
polysaccharide (immunogenic) and lipid part of LPS, is Lipid A which is toxic component.
Endotoxins are part of outer portion of cell wall of Gram negative bacteria
Cytokines also induce ____________ Complex and __________________ systems.
Alternative Complex, Coagulation systems
What is factor XII?
activate blood-clotting proteins
Factor XII (activate blood-clotting protein) lead to ?
blood clots in small blood vessels.
aka Disseminated intravascular coagulation (DIC)
What does disseminated intravascular coagulation (DIC) result in ?
-acute respiratory distress syndrome
Another example of nonprotein toxin is ?
membrane blebs (Bordetella pertussis - Whooping cough) ex of a pathogen that releases part of their cell wall
What is mycolactone toxins?
lipid-like toxins - cytotoxic and immunosuppressive properties
ex: mycobacterium ulcerans
-emerging human pathogenreversoir - aquatic insects
ex: buruli ulcerdestructive effects on skin, soft tissues, and bones (central, west africa, central and south america, asia and australia)
What are 2 examples of mycolactone toxins?
ex: mycobacterium ulcerans
emerging human pathogen
reversoir - aquatic insects
ex: buruli ulcer-
destructive effects on skin, soft tissues, and bones (central, west africa, central and south america, asia and australia)
What is an negative impact of Buruli ulcer ?
lifelong disfigurement! (but little inflammation and pain)
What is a cluster of 3 giant biosynthetic genes?
What does infection of subcutaneous fat result in?
focus of necrotic (dead) fat containing myriads of mycobacteria in characteristic spherules formed w/in dead fat cells.
What's the secondary event of getting an infection of subcutaneous fat?
On contact with CNS, toxin is transported through the motor neurons back to the spinal cord.
Binds to ganglioside lipids at the terminus of the inhibitory interneurons,
Cleaves synaptobrevin, blocks release of glycine.
Inhibitory neurotransmitter (glycine), binds to receptors on the motor neurons and allows relaxation of muscle.
Morphology of Clostridium perfringens ..
Gram (+), bacilli, anaerobic, sporeforming
(found in intestinal tracts of humans and animals, nature)
C. perfringens is a major cause of .... ?
food poisoning; CPE released upon cell lysis in final stage of sporulation
C. perfringensis anaerobic but C. septicum is aerotolerant and infects what?
normal, healthy tissue (may be deadlier of the 2 Clostridia)
Clostridium perfringens has how many toxins produced?
What happens during Food Poisoning ?
growth of vegetative cell, alkaline conditions of small intestine stimulatesSporulation, triggering production of enterotoxin
Toxin also kills cells producing anaerobic condition to allow spores to germinate
What occurs during food poisoning?
-enterotoxin binds to brush border of small intestine, inserts into membrane leading to altered permeability -loss of fluids and ions, the exotoxin acts as superantigen stimulating T-lymphocytes.
What is the diagnostic trait of food poisoning?
abdominal cramps and watery diarrhea, but no fever, nausea / vomiting
Low temperature inhibits C. perfringens.. how to do this?
What is used to detect enterotoxin in stools (feces) ?
direct-enzyme-linked immunosorbant assay (ELISA)
What is debridement?
removal a dead tissue
problem: even with a skilled surgeon, damage to non-infected (live) tissue is a consequence -- treat w/ Hyperbaric oxygen treatment: oxygenates blood, kills anaerobic bacteria and reduces ability of surviving bacteria to produce toxin.
A consequence of debridement is non-infected tissue damage, what is used to help this?