Transcript Sept2_Lecture3

Lecture 5
The diversity of infectious disease
agents (I)
I can win an argument on any topic, against any opponent.
People know this, and steer clear of me at parties. Often, as a
sign of their great respect, they don't even invite me.
Dave Barry (1947 - )
Next two lectures:
• Pathogens in context: the diversity of life
on Earth
• Bacteria
• Viruses
• Survey of important human infectious
diseases and pathogens (including a few
eukaryotic pathogens)
The three domains of life
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Before molecular sequence-based methods it was
not possible to reconstruct the tree of life
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2 kingdoms (from Linnaeus--think Zoology and
Botany departments) became 5 (animals, plants,
fungi, “protists”, and “monera”)
•
There was also a more fundamental distinction
between organisms with nuclear membranes
(eukaryotes) and without (prokaryotes)
•
The main diversity of life was thought to be in the
four eukaryotic kingdoms (particularly the
multicellular ones)
Whittaker, 1969: the 5 Kingdoms
The three domains of life
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Carl Woese brought clarity to microbial (and in fact
all biological) diversity by comparing fundamental
gene sequences shared by all known, non-viral life
forms
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Ribosomal RNA (rRNA) comparisons indicate that
there are three “domains” of life: bacteria,
archaea, and eucarya
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The phylogenetic tree, based on molecular
sequence, became the most powerful tool to
reconstruct the history of life
The three domains of life
BACTERIA
ARCHEA
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0.1 CHANGES/SITE
EUCARYA
The three domains of life
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Phylogenetic trees are conceptually simple. They
represent educated guesses about the historical
diversification, and hence relationships, among
taxa
Consist of topology plus branch lengths. Aligned
sequences are compared and, in general, pairs of
sequences with few differences branch together
This reflects “evolutionary distance”
In reality, no single tree accurately reflects the
deep history of life because it was not treelike, but
the rRNA tree is still meaningful
The three domains of life
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It is shocking how much of the diversity of life is
microbial
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Historically biology has tended to be eukaryotically
chauvinistic …why?
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The tree of life shows that humans, and our close
kin such as plants and fungi, occupy a very narrow
slice of biological diversity
The three domains of life
BACTERIA
ARCHEA
*
0.1 CHANGES/SITE
EUCARYA
The three domains of life
BACTERIA
ARCHEA
*
0.1 CHANGES/SITE
EUCARYA
The three domains of life
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Humanity’s place on the tree of life is perhaps as
profound an insight as the Copernican revolution
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Not only are we floating on a planet orbiting a
mediocre star in a mediocre galaxy, but we’re also
just a sideshow in the diversity of life on Earth
Microbial diversity
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Classical microbiology relied on observing
bacteria/archaea down a microscope
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To do this, it was necessary first to cultivate them
in the laboratory
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They would put samples of soil, or pus, or
whatever, in various kinds of nutrient broth
Microbial diversity
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Each of would encourage the growth of different
sorts of bacteria/archaea depending on the
chemical composition
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Hence classical microbiology is the study of
bacteria/archaea that can be cultured.
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Nowadays, we can look directly at bacterial genes
without culturing and it turns out we were missing
about 99.99% of the diversity
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Fossil evidence for prokaryotic life 3.5 billion years
ago
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It took another 2 billion years or so for the
appearance of eukaryotic cells that could give rise
to larger animals and plants
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Archea may be the most diverse and massive
domain, but few are known to cause infectious
disease, so we’ll ignore them
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There are lots of beneficial bacteria:
-nitrogen-fixing bacteria in root nodules of plants
-bacteria in rumen of cattle digest cellulose of grass
-even in non-ruminants, like us, most gut bacteria
appear to be beneficial
-fermenting milk into yogurt and cheese
-alcohol
-recycling waste
-synthesizing antibiotics and enzymes
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Their metabolic and ecological diversity outstrips
eukaryotes
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In fact, most of the interesting biochemistry in
“higher” organisms is actually done by bacteria
Check out the rest of this paper: this is what you should be
aiming for with your term paper. Model the format on the “News
and Views” format of the journal “Nature”. Look at several such
articles. The journal is available online.
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Only very few bacteria of the innumerable species
are pathogenic
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Of the roughly 400 genera less than 40 contain
species that regularly cause disease in humans
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Other animals have different suites of pathogens
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But there is overlap: zoonoses are diseases that
jump occasionally from some “natural” non-human
host
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E.g. plague from rats, brucellosis from goats, TB
from cattle (which is why milk is pastuerized)
Bacterial classification
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Phenotype is actually a pretty bad guide to phylogeny
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For example photosynthesis is practiced by species
from five bacterial Kingdoms
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Traditional microbiologists drew a sharp distinction
between “Gram-positives” and “Gram-negatives”
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Named after Hans Christian Gram who found that some
bacteria, first dyed, then treated with solvent, retain the
dye
Gram-positives are a coherent group, but Gramnegatives are not
As if zoologists had classified animals into “Birds” and
“The Rest”
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Spirochaetes
•Chlamydiae and sprirochaetes are
obligate intracellular parasites of
animals
Chlamydiae and
Spirochaetes
•Chlamydia infection is often
asymptomatic
•Most common bacterial STD in
USA, with about 3 million new
infections/year
•Can cause reproductive problems,
pneumonia in newborns
•Spirochaetes include the agents of
syphilis (Tryponema pallidum) and
yaws and the agent of relapsing
fever and Lyme disease (Borrelia
burgdorferi)
Late Syphilis: Gumma On Eye
Syphilus: Treponema pallidum
Actinobacteria
a.k.a. Grampositive, high G-C
•Gram-positive bacteria include the
agents of tuberculosis,
Mycobacterium tuberculosis, and
leprosy. M. leprae
•These are both “high G-C” Grampositives
•What is “high G-C”?
•Lots of G’s and C’s relative to A’s
and G’s in their DNA
Gram-positives
Tuberculosis
Figure 10-3 part 3 of 3
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The singlemost important bacterial pathogen of
humans right now (around 2 million deaths/year)
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Most deaths in developing world, but by no means
solely there
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A.k.a. ‘consumption’: used to kill 5/1000/year in
Britain
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Accounted for many of those pale, coughing
Victorians
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Caused by Mycobacterium tuberculosis, a very
tough bacterium that is resistant to most host
defense mechanisms (why?)
Firmicutes
(including
Clostridia)
a.k.a. Grampositive, low GC content
•Among the “low G-C” ones are
-Bacillus anthracis (anthrax)
-Staphylococcus aureus (what you
don’t want to get after surgery)
-Streptococcus pneumoniae
(pneumonia, bacterial meningitis)
-Clostridium spp.(anaerobic, spores
resist boiling; causes botulism, gas
gangrene, tetanus, among other
pathologies)
-Lactobacillus (on a more friendly
note, fermenting agent for making
yoghurt)
Gram-positives
What is Tetanus?
Tetanus is an acute, sometimes fatal, disease of the
central nervous system, caused by the toxin of the tetanus
bacterium Clostridium tetani, which usually enters the body
through an open wound. The bacteria then multiply too fast
to be destroyed by the immune system. C. tetani releases
powerful poisons known as toxins that rapidly destroy
tissue.[1]
The tetanus bacterium lives in soil and manure, but also
can be found in the human intestine and other places.
Proteobacteria
proteobacteria
•Proteobacteria are a diverse and
important group also known as
purple bacteria
•Mitochondria are endosymbiotic
proteobacteria
•Traditionally divided into alpha,
beta, gamma, delta
•Epsilon has now been added
•Many proteobacteria practice
photosynthesis that is distinct from
other bacteria
proteobacteria
•Various alpha proteobacteria
form close association with
eukaryotes
Rhizobium fix nitrogen in root
nodules
•Agrobacterium is closely related
and is a plant pathogen
•Rickettsias are intracellular
pathogens of animals (e.g.
typhus/Rickettsia prowazekii)
•Rickettsias dwell within cells and
it’s not surprising that
mitochondria, which also dwell
intimately in eukaryotic cells, are
closely related
proteobacteria
•Typhus (not to be confused with Typhoid fever,
caused by Salmonella sp) is a name given to
several similar diseases caused by Rickettsia
bacteria.
•Rickettsia is endemic in rodent hosts, including
mice and rats, and spreads to humans through
mites, fleas and head, body, and pubic lice.
•The insects often flourish under conditions of
poor hygiene, such as those found in prisons or
refugee camps, amongst the homeless, or until
the middle of the 20th Century, in armies in the
field.
Typhus in history
The city-state of Athens in ancient Greece was hit by a devastating epidemic, known as the Plague of Athens, during
the second year of the Peloponnesian War (430 BC), which killed, among others, Pericles and his two elder sons.
The plague returned twice more, in 429 BC and in the winter of 427/6 BC. Epidemic typhus is one of the strongest
candidates for the cause of this disease outbreak
Combatant deaths due to typhus were obviously a serious factor during European conflicts. Major outbreaks
occurred during the liberation of Spain, the English Civil War, the Thirty Years' War, and during Napoleon's failure in
Russia.
In World War I, de-lousing stations were established for troops on the Western front but the disease ravaged the
armies of the Eastern front, with over 150,000 dying in Serbia alone. Fatalities were generally between 10 to 40
percent of those infected, and the disease was a major cause of death for those nursing the sick.
Thousands of prisoners held in appalling conditions in German concentration camps such Theresienstadt and
Bergen-Belsen died of typhus during World War II.
Typhus was also a killer in civilian populations throughout history. In London, typhus frequently broke out among the
ill-kept prisoners of Newgate Gaol and then moved into the general city population. An outbreak in 1557–59 killed
about 10 percent of the English population.
In Russia after World War I, in the civil war between the White and Red armies, typhus killed three million, largely
civilians.
•Beta proteobacteria include
Neisseria gonorrhea
proteobacteria
Bordetella pertussis
(whooping cough)
•Deltas/epsilons include
-Bdellovibrioi which acts like a
guided missile and attacks other
bacteria by rushing at them at 100
cell lengths per second and boring
in at 6000 rpm
-Helicobacter pylori the agent of
stomach ulcers
Meningitis
Neisseria spp.
Haemophilus influenzae
•Gamma proteobacteria include
several important pathogens,
including:
proteobacteria
-Escherichia coli
-Shigella
-Salmonella
(Typhoid fever)
-Vibrio
(Cholera)
-Legionella
-Yersinia pestis
(plague)
-Haemophilus influenzae
(pneumonia)
•Supremely important ecologically
Cyanobacteria
•Used to be called “blue-green
algae”
•Ubiquitous green scum
responsible for a lot of the world’s
photosynthesis
•Chloroplasts are endosymbiotic
cyanobacteria
•Anyone know of a pathogenic
cyanobacterium?
Figure 10-3 part 3 of 3
Figure 10-3 part 3 of 3
Chest X-Ray, with pneumonia.
Acute respiratory illnesses
Figure 10-3 part 3 of 3
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Respiratory infections, including pneumonia, are a
big class of human pathogens
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Streptococcus pneumoniae among the most
common causes of pneumonia
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Causes desperate illness, blue color, gasping for
breath
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Other important bacterial respiratory pathogens
include Bordetella pertussis (whooping cough)
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Haemophilus influenzae (pneumonia and
meningitis) (Why’s it called that!?)
Figure 10-3 part 3 of 3
Diarrheal diseases
Figure 10-3 part 3 of 3
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Taken together, pathogens causing diarrhea are
among the most lethal
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More than 2 million deaths/year, mostly
developing world, mostly children
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Very easy to prevent and treat in many cases
•Epidemic Cholera Vibrio cholerae
•Cholera is an acute, infectious disease characterized by extreme
diarrhea, vomiting, and cramps.
•The cholera bacteria produce a toxin which keeps the human body
from absorbing liquids.
•It is one of the most rapidly fatal illnesses known. Untreated
individuals may die from severe dehydration within two to three
hours. This disease has been the killer of millions worldwide. It is
endemic in both Bangladesh and Peru
• In 1991, a cholera epidemic swept down the west coast of South
America. Africa suffered a similar cholera surge in 1991.
•It seems that the bacteria prefers brackish coastal waters
(moderately salty waters, i.e., coastal estuaries).
Epidemic Cholera Vibrio cholerae
•The bacteria is controlled by chlorination of water and by
waste water management. Of course, the less developed
nations with their less developed water and waste systems are
more at risk of outbreaks than the more developed nations.
•Natural disasters can greatly heighten the cholera risk by
damaging the water and waste water systems.
•Today . . . “Cholera can be simply and successfully treated by
immediate replacement of the fluid and salts lost through
diarrhea. Patients can be treated with oral rehydration solution,
a prepackaged mixture of sugar and salts to be mixed with
water and drunk in large amounts. This solution is used
throughout the world to treat diarrhea”
Other bacterial diarrhea-causing bugs:
•Shigella
•Salmonella (including S. typhi, the typhoid bacillus)
•E. coli 0157
•Collectively known as the “enterics”
•There are also important protozoan and viral agents of
diarrhea
Figure 10-3 part 3 of 3
Figure 10-3 part 2 of 3