Download not considered life!

Medical Microbiology
and
Parasitology
Stijn van der Veen
Website for the course

Website: http://m-learning.zju.edu.cn

All basic course information
 Course introduction and outline
 Lecture slides
 Basic information teachers
 Online quizzes
Assessment & final mark

Attendance at lectures and lab (10%)

Online quizzes (20%)

Laboratory reports (10%)

In-class-quizzes (10%)

Final exam (50%)
Attendance

Attendance will be monitored at the beginning
of class

Being late for more than 20 minutes will be
considered as absent.

Not allowed to attend final exam when absent
for more than 70% of total lectures and lab
Online quizzes

5 quizzes

Each online quiz consists of 20-30 multiple choice
questions

Students who missed the first attempt will be given one
more chance to retake the quiz.

The maximum score for retaking quiz will be 60

If you missed the quiz, please contact with teacher
assistants.
Laboratory reports

Reports submitted after the deadline will be recorded
as late

Late submissions will incur a penalty of 10% per
day

Absence of a report will normally result in a score of 0
for that particular class
In-class-quizzes

The time and format of in-class-quiz depends
on each teacher
Final exam

Multiple choice questions （50 questions, 50 points）

True or false （20 questions, 20 points）

Short answer questions （4-5 questions, 30 points）
Introduction
to
Medical Microbiology
What is a Microbe?

Microbes are (single-)cell organisms so tiny that millions can fit
into the eye of a needle.

They are the oldest form of life on earth. Microbe fossils date
back more than 3.5 billion years to a time when the Earth was
covered with oceans that regularly reached the boiling point,
hundreds of millions of years before dinosaurs roamed the
earth.

Without microbes, we couldn’t eat or breathe.

Without us, they’d probably be just fine.

Understanding microbes is vital to understanding the past and
the future of ourselves and our planet.
What is a Microbe?

Microbes are everywhere. There are more of them on a
person's hand than there are people on the entire planet!

Microbes are in the air we breathe, the ground we walk on, the
food we eat—they're even inside us!

We couldn't digest food without them—animals couldn't, either.
Without microbes, plants couldn't grow, garbage wouldn't
decay and there would be a lot less oxygen to breathe.

In fact, without these invisible companions, our planet wouldn't
survive as we know it!
How small are microbes?
meter
Naked eye
Perspective
meter
Sun
Tapeworm
1
109
10-1
108
Jupiter
Nematode
10-2
107
Schistosome
10-3
106
Earth
Moon
Light microscope
10-4
Thiomargarita
namibiensis
105
Tryptanosome
10-5
104
Plasmodium
Bacillus cereus
10-6
Staphylococcus
Pox virus
10-7
103
Burj
Khalifa
Electron microscope
102
Medical
school
Influenza virus
10-8
101
Polio virus
10-9
Mount
Everest
Human
1
Microbes in the Tree of Life
Protista
Viruses?...not considered life!
Taxonomy (biological classification)
Carolus Linnaeus

Proposed the binomial nomenclature to
standardize names for all living things.

Organisms are given two Latinized
names:

Generic name (Genus)
 Specific name (Species)

Names are always in Italics

Genus name is capitalized, species
name not.

Second time use in text: genus name
can be initialized
Carolus Linnaeus: 1707 – 1778
Examples
Bacteria
Archaea
Eukaryota
(not used)
(not used)
Animalia
Proteobacteria
Euryarchaeta
Chordata
Gammaproteobacteria
Thermococci
Mammalia
Enterobacteriales
Thermococcales
Carnivora
Enterobacteriaceae
Thermococaceae
Canidae
Escherichia
Pyrococcus
Canis
E. coli
P. abyssi
C. lupus
Types of microbes
Viruses
Unable to do much of anything on their own, viruses go into host cells to
reproduce, often wreaking havoc and causing disease. Their ability to move
genetic information from one cell to another makes them useful for cloning
DNA and could provide a way to deliver gene therapy.
Bacteria
Often dismissed as “germs” that cause illness, bacteria help us do an
amazing array of useful things, like make vitamins, break down some types
of garbage, and maintain our atmosphere.
Archaea
These bacteria look-alikes are living fossils that are providing clues to the
earliest forms of life on Earth.
Protista
Plant-like algae produce much of the oxygen we breathe; animal-like
protozoa (including the famous amoeba) help maintain the balance of
microbial life.
Fungi
From a single-celled yeast to a 3.5-mile-wide mushroom, fungi do
everything from helping to bake bread to recycling to decomposing waste.
Viruses

Acellular

Consist of DNA or RNA core

Core is surrounded by a protein coat

Coat may be enclosed in a lipid
envelope

Viruses are replicated only when
they are in a living host cell

Not considered life,…but this is still
a debate
Bacteria

Prokaryotes

Cell wall contains peptidoglycan

Replicate by binary fission

Use organic chemicals, inorganic
chemicals, or photosynthesis for energy

Come in many shapes
Archaea

Prokaryotes

No peptidoglycan (some have
pseudopeptidoglycan)

Replicate by binary fission,
fragmentation, or budding

Use organic chemicals, inorganic
chemicals, or photosynthesis for energy

Live everywhere, including extreme
environments

Methanogens
 Extreme halophiles
 Extreme thermophiles
Protista

Eukaryotes

Replicate sexually or by binary
fission

Use sunlight or absorb or ingest
organic chemicals for energy

May be motile via pseudopods, cilia,
or flagella

Live mostly free, but some are
parasites
Fungi

Eukaryotes

Chitin cell walls

Use organic chemicals for energy

Sexual or asexual reproduction through
spores and mycelial fragmentation

Molds and mushrooms are multicellular

Yeasts are unicellular
Infectious diseases

Major impact on life expectancy

Bronze age => 26 yrs
 Medieval times => 30 yrs
 End of 19th century => 50 – 64 yrs
 Now world average => 71 years
First recorded perception of micro-life
Aristotle

Theory of spontaneous generation
of life from nonliving matter.

Aristotle said: “it is readily
observable that aphids arise
from the dew which falls on
plants, fleas from putrid matter,
mice from dirty hay.”
Aristotle: 384 – 322 B.C.
Challenge of spontaneous generation
Francesco Redi

Where do maggots come from?
Experiment
 Left open
 Maggots
developed
 Covered
with netting
 Maggots on
netting
Jar 1
Jar 2
 Sealed
 No maggots
Jar 3
Francesco Redi: 1626 – 1697
First microscopes
Antonie van Leeuwenhoek

Grandfather of microbiology

His interests in lens making resulted
in the first microscopes.

He discovered tiny organisms that
were invisible to the naked eye and
called these “animalcules”.
Antonie van Leeuwenhoek: 1632 - 1723
Poem about Van Leeuwenhoek
Maxine Kumin:
The Microscope
Anton Leeuwenhoek was Dutch.
He sold pincushions, cloth, and such.
The waiting townsfolk fumed and fussed,
as Anton’s dry goods gathered dust.
He worked, instead of tending store,
At grinding special lenses for
A microscope. Some of the things
He looked at were: mosquitoes’ wings,
the hairs of sheep, the legs of lice,
the skin of people, dogs, and mice;
ox eyes, spiders’ spinning gear,
fishes’ scales, a little smear
of his own blood, and best of all,
the unknown, busy, very small
bugs that swim and bump and hop
inside a simple water drop.
Impossible! Most Dutchmen said.
This Anton’s crazy in the head!
We ought to ship him off to Spain!
He says he’s seen a housefly’s brain!
He says the water that we drink
Is full of bugs! He’s mad, we think!
They called him dumkopf, which means dope.
That’s how we got the microscope.
First vaccine
Edward Jenner

Father of immunology

Used cowpox inoculation, which
causes mild symptoms, to protect
against smallpox.

At that time it was estimated that 20%
of the population died of smallpox, so
he saved many lives.
Edward Jenner: 1749 - 1823
Smallpox

Caused by the virus Variola major and
Variola minor

Deadly disease with 30-35% mortality
rate

Survivors often suffer from
disfigurement and blindness.

Caused 300-500 million deaths in the
20th century

Through a widespread vaccination
program WHO managed to eradicate
smallpox in 1979
Notable victims include:
Queen Mary II of England
Emperor Joseph I of Austria
King Luis I of Spain
Tsar Peter II of Russia
King Louis XV of France
Birth of the germ theory of disease
Oliver Holmes

Published in 1843 a paper on "The
Contagiousness of Perpetual Fever”

Perpetual fever or childbed fever was
very common and had a mortality rate
of 10-35%

The paper stated that perpetual fever is
passed on from patient to patient via
contacts with their physician
Oliver Holmes: 1809 - 1894
Perpetual fever

Fever that is associated with an infection of the
female reproductive organs.

Usually contracted as a result of childbirth or
miscarriage.

Most common agent of the infection is
Streptococcus pyogenes.

Other diseases caused by S. pyogenes:




Strep Throat
Streptococcal Pneumonia
Scarlet fever
Necrotizing fasciitis
Birth of the germ theory of disease
Ignaz Semmelweis

Investigated the cause for
higher death rates due to
perpetual fever in the maternity
wards staffed by medical
students than in those by
midwives.

He linked this to the common
practice of postmortem
examination and the transfer of
cadaverous material by the
students

He introduced policy of hand
washing with chlorinated lime
Ignaz Semmelweis: 1818 - 1865
Hand washing is important
Hand washing is vital in healthcare
settings to remove pathogenic microorganisms!!!

The World Health Organization has "Five
Moments" for washing hands





Before patient care
After environmental contact
After exposure to blood/body fluids
Before an aseptic task
After patient care
Birth of the germ theory of disease
John Snow

Father of epidemiology

In 1854, he investigated the source of a
cholera outbreak in London.
John Snow: 1813 - 1858

He traced it to a water pump on Broad
Street.

He had the pump disabled, which
ended the outbreak.

His work resulted in changes and
improvements to water (waste)
systems all over the world.
Original map of the outbreak
Cholera

Infectious gastroenteritis cause by bacterium
Vibrio cholerae.

Generally transmitted through contaminated
water or food.

Damage of mucosal epithelium in small
intestine resulting in massive diarrhea and
fast dehydration.

Killed tens of millions of people in epidemics
in the 19th and 20th century.

Still affects 3-5 million people annually, with
an estimated 100,000 deaths.
Pasteurization & fermentation
Louis Pasteur

Father of microbiology

With his growth and fermentation experiments
he conclusively proved the theory of biogenesis.
Louis Pasteur: 1822 - 1895

Demonstrated that spoilage organisms could be killed by heat
that was not hot enough to evaporate the alcohol in wine.

This application of a high heat for a short time is called
pasteurization.
Attenuated vaccines

He worked on ways to prevent chicken cholera.

Due to neglect of his assistant, old culture were
used to inoculate chickens. Chickens recovered
and became immune.

The bacteria had become weakened (attenuated).

He named these artificially weakened infectious
diseases “vaccines”.

He produced the first attenuated vaccine for rabies
by drying the nerve tissue of infected rabbits.
Rabies vaccine

In 1885, a young boy, Joseph Meister, had been bitten by a
rabid dog, and was brought to Pasteur. The boy almost
certainly would have died an agonising death if nothing was
done so Pasteur took the risk on using his untested vaccine.

"The death of this child appearing to be inevitable, I decided, not without lively
and sore anxiety, as may well be believed, to try upon Joseph Meister, the
method which I had found constantly successful with dogs. Consequently, sixty
hours after the bites, and in the presence of Drs Vulpian and Grancher, young
Meister was inoculated under a fold of skin with half a syringeful of the spinal
cord of a rabbit, which had died of rabies. It had been preserved (for) fifteen
days in a flask of dry air. In the following days, fresh inoculations were made. I
thus made thirteen inoculations. On the last days, I inoculated Joseph Meister
with the most virulent virus of rabies."
© 2000-2015 HistoryLearningSite.co.uk
Rabies

Rabies is a viral infection of the brain caused
by lyssavirusses

Generally transmitted by bites from infected
dogs or bats

It is almost 100% deathly unless treated with
vaccines or immunoglobulin within 10 days of
infection

Rabies causes about 26,000 to 55,000 deaths
worldwide per year
Source: Black et al. Sci. Transl. Med. (2012) 29: 123ps5
Koch’s postulates
Robert Koch

Founder of modern bacteriology

Koch’s postulates, linking microorganisms to disease
Robert Koch: 1843 - 1910

Identified the causative agents for
cholera, anthrax, and tuberculosis,
thereby proving the concept of
infectious diseases.

Improved laboratory techniques and
introduced bacterial agar and the Petri
dish to purify bacterial colonies
Koch’s postulates
 The organism must always be
present, in every case of the
disease.
 The organism must be isolated
from a host containing the disease
and grown in pure culture.
 Samples of the organism taken
from pure culture must cause the
same disease when inoculated into
a healthy, susceptible animal in the
laboratory.
 The organism must be isolated
from the inoculated animal and
must be identified as the same
original organism first isolated from
the originally diseased host.
Anthrax

Lethal disease caused by the bacterium
Bacillus anthracis.

Pulmonary or respiratory
 Gastrointestinal by consumption of infected meat
 Cutaneous through skin lesions

Common organism present in the soil.

B. anthracis can form dormant endospores that
are able to survive for centuries.

Used for development of biological weapons.

First vaccines developed by Pasteur.
Antiseptic surgery
Joseph Lister

Father of modern surgery

Gangrene or wound rotting was a major
problem associated with surgery

Heard about work from Pasteur and
promoted sterile surgery.

Introduced carbolic acid (phenol) to
clean wounds and sterilize surgical
instruments.
Joseph Lister: 1827 - 1912
First antimicrobial agents: arsphenamine
Paul Ehrlich

Initiating and named the concept of
chemotherapy.

His lab synthesized Arsphenamine,
which is also known as Salvarsan or
compound 606.

Arsphenamine was the first effective
medical treatment for syphilis

Arsphenamine was very unstable,
oxygen sensitive and later replaced by
penicilin
Paul Ehrlich: 1895-1964
Syphilis

Syphilis is a highly contagious sexually
transmitted disease caused by the
bacterium Treponema pallidum

Syphilis develops in several different
stages

Primary syphilis manifests as a single sore
(chancre) at the site of infection around 10-90 days
after exposure and last for 3-6 weeks.
 Secondary syphilis shows as a body rash with
possible fever, swollen lymph glands, sore throat,
hair loss, headaches, weight loss, muscle aches,
and fatigue.
 Latent syphilis is without any symptoms
 Tertiary syphilis develops on 1/3 of infected people
and can appear 3-20 after infection. At this stage
the disease is no longer contagious and it comes in
many different forms such as paralysis, numbness,
gradual blindness, and dementia.
First antimicrobial agents: sulfonamides
Gerhard Domagk

Discovered the first antimicrobial agent
sulfanilamide / sulfonamide

Discovered that the sulfanilamide
portion of the dye Prontosil was
effective against bacteria.

Sulfanilamide was later replaced by
penicillin's, but it eventually led to the
development of the anti tuberculosis
drugs thiosemicarbazone and isoniazid.
Gerhard Domagk: 1895-1964
Tuberculosis

Widespread disease caused by the bacterium
Mycobacterium tuberculosis.

It is estimated that 1/3 of the world population is
infected with M. tuberculosis.

Typically a lung disease but can also affect other
parts of the body.

During the latent stage it is encapsulated and
dormant, but it can reactivate and spread.
Tuberculosis
Death from tuberculosis per 100,000 inhabitants in 2004
First antimicrobial agents: penicillin’s
Alexander Fleming

Observed that colonies of the
bacterium Staphylococcus aureus
disappeared on plates contaminated
with a mold

He identified the mould as a Penicillium
called the active substance from his
mold juice penicillin.

Later he had only limited success in his
clinical trials and found working with the
mold and extracting the penicillin to
large scale quantities to difficult, so he
basically abandoned it.
Alexander Fleming: 1881-1955
Staphylococcus aureus

A very versatile bacterium that is often
found on the human skin and in the
respiratory tract.

It is asymptomatically carried by approx.
20% of the human population.

Can cause a wide variety of diseases
ranging from minor skin infections to
dangerous diseases such as wound
infections, sepsis, meningitis, pneumonia
or bacteremia.

Notorious for hospital acquired infections
and for developing antibiotic resistance
(MRSA).
First antimicrobial agents: penicillin’s
Florey & Chain & large team

Continued research on penicillin at the
Sir William Dunn School of Pathology
in Oxford.

They managed to find a process for
mass production

Howard Florey: 1898-1968
Proposed the correct chemical
structure of penicillin
Ernst Boris Chain: 1906-1979
Fight against infectious diseases
Main determinants for our success of
limiting infectious diseases

Improved hygiene conditions

Vaccination

Antibiotics
Next lecture

Bacterial Cell Structures