Lecture 5: Mucusal Infections Flashcards
Merkel cells
one of the first transformative viruses identified (cancer causing)
Enteric Bacterial Pathogens
E. Coli (EPEC and EHEC (enteropathogenic and enterohemorrhagic)
Shigella (dysenteriae)
Salmonella (serovar typhi and serovar typhimurium)
Yersinia (enterocolitica)
Enteric Bacterial Pathogens
E. Coli (EPEC and EHEC (enteropathogenic and enterohemorrhagic)
Shigella (dysenteriae)
Salmonella (serovar typhi and serovar typhimurium)
Yersinia (enterocolitica)
Core and Pan Genome of Enteric Bacteria: Core of EHEC, Shigella, and Salmonella
Gram Negative
Bile salt resistant
Bile start and studying enteric bacteria
streak fecal matter on plate with bile salt
things that arent enteric will die
study whats left
Shigella vs. the other species
was though to be different until recently
BUT: found that shigella is an E. Coli that lost some genes and gained a few plasmids
“subspecies of E. coli” say som
special things about EHEC
T3SS
urea gene
lactose gene
Special things about Salmonella
two T3SSs
ability to H2S
STUDY TO CORE-PAN GENOME FIGURE
STUDY TO CORE-PAN GENOME FIGURE
How E. coli causes diarrhea
1) inhibits absorptive function of intestine
2) opens tight junctions between cells (bloody)
3) causes inflammation
diarrhea
caused by excess fluid in GI tract
intestines absorb water usually, in this case they dont
feces become thinner
Caused by inflammation OR an actual function of the bacteria
how cholera causes diarrhea
causes epithelial cells to pump salt into the lumen of the gut
water rushes into gut from body
rice water diarrhea
active function of toxin
how cholera causes diarrhea
causes epithelial cells to pump salt into the lumen of the gut
water rushes into gut from body
rice water diarrhea
active function of toxin
pathotypes
groups of bacteria that cause disease in a certain way
who has E. coli
most mammals, usually doesn’t cause disease
ETEC
enterotoxin e.c.
most common
produces a toxin that produces a protein that degreulates water absoprtion of intestines
TRAVELER’s diarrhea
EIEC
enteroinvasive e.c. mild diarrhea the one that evolved into shigella can invade host cells-lives at epi layer pretty self-limiting: goes away on its own often get traveling
EPEC
enteropathogenic e.c.
major cause of infant dirrhea and death oitside US
ADHERES tightly to epi cells
serious inflammation
EHEC
enterohemorrhagic E.c. bloody diarrhea sometimes a problem in the US its EPEC plus a toxin: SHIGA TOXIN destroys epithelial cells, blood goes into lumen of the gut... pretty bad
EHEC
enterohemorrhagic E.c. bloody diarrhea sometimes a problem in the US its EPEC plus a toxin: SHIGA TOXIN destroys epithelial cells, blood goes into lumen of the gut... pretty bad
more on EHEC
lose some genes from EPEC
add a toxin
one of worst enteric infections you can get
more on EHEC : US strain
O157 H7 (these are ANTIGENS) we have the strongest response to these 2 antigens HEMORRHAGIC diarrhea has shiga toxin fecal contamination of undercooked foods
EHEC: what does O157 mean
O=LPS
157=bloody diarrhea
EHEC: what does H7 mean?
FLAGELLA
EHEC secretion
LEE type 3 secretion system
CAUSES PEDESTAL FORMATION
what is HEmorrhagic diarrhea
bright red blood
EHEC
Pedestal formation
cause actin to polymerize underneath the bacteria
this lets the bacteria move pretty well?
DECREASES SURFACE AREA of epithelial cells
EHEC transmission
mostly foodborne
because it has a requires a high infectious dose
EPEC secretion
secrete proteins into the host
bacteria stick to the bacterial protein
this causes actin to polymerize under the bacteria
other proteins secreted lead to death of host cell… bacteria eventually kills the host cell by apoptosis because thats the only way the bacteria can get off the surface
How EHEC differs from EPEC
because it also has a bacteria phage that contains the SHIGA TOXIN
shiga toxin: A-B toxin
B part of protein : sticks to cell sruface
A part of protein: has catalytic activity that kills the cell
How shiga toxin kills the cell
retrograde transport
retrograde transport
vesicle meant to go outside moves backwards
vesicle fueses with the Golig again, eventually the ER again
in the ER: the B portion forms a pore, A goes to cytosol, finds RIBOSOME
A and ribosome
a portion cleaves the ribsomal RNA
this stops protein synthesis
cell dies because it cant make proteins
shiga toxin: A-B toxin
B part of protein : sticks to cell sruface 5 of them
A part of protein: has catalytic activity that kills the cell 1 of them
A and ribosome
a portion cleaves the ribsomal RNA
this stops protein synthesis
cell dies because it cant make proteins
WATCH VIDEO ON SLIDE 26 IT WILL BE ON EXAM
WATCH VIDEO ON SLIDE 26 IT WILL BE ON EXAM
importance of shiga toxin being on a phage
it can jump into other strains
what B subunit binds to (EHEC)
GB3
amount of GB3
decreases as you age
more in men/boys
so who gets most sick from EHEC infection?
young boys
they have the most GB3, which the Shiga toxin can take advatage of
what does shiga toxin effect
gut
kidneys
nervous system
(where GB3 is found)
people who survive EHEC…
severe kidney and sometimes brain damage
what does shiga toxin do to BODY
causes clots to form in small blood vessles
RBCs damaged: ANMEIA
kidney filtration decline… HUS (hemulytic-uremic syndrome)
what does T3SS do?
secretes proteins from gram neg bact to euks cells
DOES NOT secrete shiga toxin
so why does EHEC cause bloody diarrhea
break down of tight junctions
shiga toxin causes clots in capplaiers… blood builds up in liamina propria
destroy surface and underlying tissues
why is EHEC an American disease
non-human reservoir is COWS
which we don’t threat the best… and Indians cows dont have O157 H7
our cows eat feces of other cows… most of the get O157 H7
we get it in produce a lot bc its sprayed with cow feces
Pedestal formation ???? LOOK INTO
adhesion to cells?
DECREASES SURFACE AREA of epithelial cells
why is EHEC an American disease
non-human reservoir is COWS
which we don’t threat the best… and Indians cows dont have O157 H7
our cows eat feces of other cows… most of the get O157 H7
we get it in produce a lot bc its sprayed with cow feces
Shigella
dysentery
intracellular pathogen
very low infectious dose-waterborne
why does Shigella have a low infectious dose
it lost the genes it didnt need for infection
also: it infects by entering the M cells of pyers patches…lyses M cells when it gets inside, then pushes to neighbors using actin polymerization and replicates and repeats
ALSO: avoids immune cells other than NK (whic mostly recognizes VIRUSES, not BACT) and CD8 cells
how are Shigella nd E. coli different
Shigella CANNOT ferment lactose
how are Shigella nd E. coli different
Shigella CANNOT ferment lactose
Shigella is a ______pathogen
specialized
evolution of shigella
evolved to be good at SPREADING, doesnt need host for long
so doesnt really care if it kills the host
Characteristics of specialized pathogens
don’t care if they kill host
Shigella, Norovirus
wants you to produce a lot of feces so it can spread more, doesnt care if you die after a week
often waterborne diseases
Salomnellosis found in
chickens, eggs
birds
reptiles
oysters
salmonellosis in chickens
doesnt cause disease in chickens
but all chicken meat in oregon had it after processing due to the washing process to reduce pathogens
so why isnt everyone there dying: there isnt enough bacteria in the meat to make people sick
how to avoid salmonella in food
wash and cook chicken
use different utensils for food prep of chicken and produce
salmonella and egs
bacteria can move across the shells
so dont eat raw eggs in cookie dough you make
salmonella serovars
Typhumurium
Typhi
Salmonella enterica Typhi
Typoid fever infects and lives off macrophages, goes from one to another... rides them to liver and spleen... fever and death 2 T3SSs pilli flagella
Typoid mary
she was a carrier shedding infectious agents
first time we realized this is possible
salmonella-containing vesicles
get out via normal endocytic pathway
2 T3SSs of salmonella typhi
1) gets into epi cells
2) helps for survival in macrophages
how Salmonella enterica Typhi is different from plague
typhi enters through M cells, less at a time, tends to be more self-limiting
plauge: lots of bacteria enter the body at once, quick death
Salmonella enterica Typhi vaccine
live bacteria with ONE T3SS and a plasmid for living in the macrophages removed
vaccine gets into macrophage and then dies
2 T3SSs of salmonella typhi
1) gets into epi cells
2) helps for survival in macrophages
changes how the macrophage sees the bacteria.
2 T3SSs of salmonella typhi
1) gets into epi cells
2) helps for survival in macrophages
changes how the infected macrophage sees the salmonella containing endosome so that it DOESNT fuse it with a lysosome, which would kill it
Salmonella enterica Typhi vaccine
live bacteria with ONE T3SS and a plasmid for living in the macrophages removed
vaccine gets into macrophage and then dies
typhoid in the world
tends to be endemic
control of human feces=less of a problem
Salmonella enterica Typhimurium
mouse typhi… also found in chickens a lot
only causes enteritis in humans… just bad diarrhea, doesnt go to spleen and liver like typhi
cold and warm blooded vertebrates
Typhimurium vs. Typhi: genes
Typhimurium: lots of genes, can live in birds, reptiles, amphibians
Typhi: lost many genes, specailized in infecting humans
Typhimurium vs. Typhi: peudeogenes as a portion of genome
Typhimurium: 0.6%
Typhi: 5%
pseudogenes are genes that have LOST function. (more in typhi=it doesnt need 5% of its genome)
Typhimurium vs. Typhi: getting nutrients
Typhimurium: prototroph: ability to synth all amino acids, nucleic acids, vitamins
Typhi: Auxotroph: needs supplementation for ceretain nutrients (tryptophan and cystine in this case)
are humans prototrophs or auxotrophs
auxotrophs,,, we need vitamins and minerals
review graph on slide 24
review graph on slide 24
1940s: decrease in Typhoid fever due to
sanitation in suburbs
typhoid used to be a city disease bc they were dirty
rising slamonellosis due to
more processed foods
outbreak then decrease in salmonellosis
huge outbreak
then sanitation in processing plants
the water bath thing
Pedestal formation ???? LOOK INTO
adhesion to cells?
see picture on slide 8
DECREASES SURFACE AREA of epithelial cells
outbreak then decrease in salmonellosis
huge outbreak
then sanitation in processing plants
the water bath thing
Pan-Core genome figure for exam
core genome lets bacteria survive in intestines of vertibrea
how we differentiate species
evolution
shigella and typhi
reduction in genes
salmonella
more genes
but severe disease because its not meant for humans
E. coli
normal flora, but can cause disease if genes move around (like the shiga toxin)
