Biology 103 - Microbes and You

Lecture 17 Outline

What is E.coli? (emerging infections)


Necrotizing fasciitis patient

Necrotized leg

Micrograph of Ebola virus

An Ebola patient

Micrograph of Marburg virus

Protective spacesuit

Doctor in protective spacesuit

Virulence Factors
What makes a friendly bacteria like Escherichia coli turn pathogenic?
It picks up new traits through mutation of its own genes or by acquiring genes from other organisms.
E.coli O157:H7, the deadly E.coli on the nightly news, is an E.coli that has acquired new genes that increase its virulence (toxicity) from another microbe
When a microbe dies some of its genetic material may survive to be taken up by another microbe.
The uptake of external DNA is called transformation
the free DNA may be in the form of plasmids (independent, small, closed, circular DNAs that carry genes)
Microbes may also acquire DNA, and hence new genes, from bacteriophages
during the bacteriophage lysogenic cycle, when induction occurs, genes from the bacteriophage host can become incorporated into the progeny viruses
when such a virus was to attack another microbe, it can transfer these genes to the new host
the transfer of genes from one species of bacteria to another is called horizontal transfer of genes (as opposed to the vertical transfer genes through heredity)

E.coli O157:H7
acquired several new genes for virulence factors
most important is the Shiga-like toxin called Vero toxin
Vero toxin is a small protein that acts to cleave the host cell's rRNA (ribosomal RNA) and hence disrupt protein biosynthesis by ribosomes
many bacteria produce toxic proteins called enterotoxins: Cholera, pertussis
the Shiga toxins are from Shigella dysenteriae, the causative agent of epidemic dysentery (bloody diarrhea)
the deadly E.coli picked up the gene for Vero toxin from a bacteriophage that presumably had previously infected Shigella
the deadly E.coli has also acquired new hemolysins that kill red blood cells by forming pores in their membranes
and this E.coli strain has new adhesins that attach better to intestinal cells
E.coli O157:H7 causes enterohemorrhagic disease
Epithelial (border) cells in the intestines and blood vessels are killed and hemorrhaging occurs
this causes a loss of fluid from the circulatory system (hypovolumia)
eventually there is kidney failure, shock, and death

Necrotizing fasciitis
the flesh-eating bacteria
really just Group A Streptococcal infection, the same bacteria that causes "strep throat"
but some strains have acquired new virulence factors
in this case, the new genes again code for exotoxins and hemolysins
two new exotoxins: a protease that degrades host cell proteins and a "superantigen" that so excites the immune systems that it causes healthy cells to commit suicide (cytokines, programmed cell death, apoptosis)
the flesh-eating bacteria may be contacted from aerosols released by a sneeze or cough of a Strep A infected individual
if it enters the body through a cut or abrasion on the skin, then it may infect the fascia tissue between the skin and the muscles
it rapidly kills tissues causing gangrene conditions
early treatment with antibiotics and removal of infected tissue can avert amputation or death
however, the death rate is 20-50%
other Group A Streptococci have acquired virulence factors: Scarlet fever toxin, Streptococcal Toxic Shock Syndrome

Ebola virus
a filovirus with ssRNA similar to the less deadly Marburg viruses
four types of Ebola: Zaire, Sudan, Reston, Tai
Zaire and Sudan cause epidemics
Reston in only found in monkeys
only one case of Tai reported
transmission from close person to person contact and body fluids
corpses are still highly infectious and monkeys can act as a vector
Reston is airborne, but the others aren't, yet.....
Zaire strain is 90% fatal
Sudan strain is 60% fatal
the disease is a hemorrhagic fever
blood vessel are attacked leading to hypovolumia and shock
liver cells and macrophages are also attacked
the result is multiple organ failure and death
so far, epidemics have been small and a vaccine may be coming soon
infection with Ebola usually evades detection by the immune system and no antibodies are made
last epidemic was in Zaire in 1995

Dengue hemorrhagic fever
a milder Dengue fever is known that can sometimes turn into Dengue hemorrhagic fever
it is caused by an arbovirus similar to the Yellow Fever agent
causes typical capillary leak syndrome and loss of blood, leading to shock and death
Dengue also attacks the liver and phagocytes
transmission is through a day-biting mosquito vector
the only reservoirs known for Dengue are humans and mosquitoes
epidemics occur mainly in tropical urban areas

Lassa virus
this arenavirus has a segmented ssRNA genome and is enveloped
Lassa virus is relatively endemic in West Africa with 40% of people in Sierre Leone carrying antibodies against Lassa (and presumably exposed)
there are 200,000-400,000 cases per year
with treatment: 15% dead; without treatment: 60% dead
disease progresses through high fever and flu symptoms, to rash and abdominal pain, and finally encephalitis (brain-swelling), multi-organ failure and death, all in about two weeks
in children it is called the swollen baby syndrome
Lassa is transmitted through a rodent vector being present in rodent blood, urine and saliva
Lassa can also be transmitted person-to-person through body fluids and sometimes through aerosols
an antiviral drug called ribavirin can be helpful in some cases

Western blots
back to some genetic engineering techniques
remember, we can use gel electrophoresis to separate proteins of different sizes
now we want to see if our "protein of interest" is one of the protein bands on the gel
first we transfer the protein in our gel into a special piece of paper (a nitrocellulose membrane) using electrophoresis, moving the proteins (as two-dimensional array) from the gel and onto the paper
the proteins are now stuck to the paper in exactly the band pattern of the gel
then we use antibodies that are specific for only our protein of interest
these bind to only our protein band
then we add a second antibody that is specific for the first antibody
this second antibody has a "reporter" on it, something radioactive, or an enzyme activity that makes a colored product
this we can see and know if our protein of interest is present
this technique is called a Western blot

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