Introduction to Medical Microbiology

Di Qu (瞿涤)

MOH&MOE Key Lab of Medical Molecular Virology

School of Basic Medical Sciences
Shanghai Medical College of Fudan University
复旦大学上海医学院分子病毒学
教育部/卫生部重点实验室
Tel：54237524
dqu@shmu.edu.cn
Chapter 1, 3
 Key Words
Medical microbiology
PROKARYOTES
 Eubacteria : Bacteria Mycoplasma,
Chlamydia, Spirochetes, Rickettsia,
Actinomycetes
 Archaea (enviroment)
EUKARYOTES: Fungi
NOT CELL
 Virus
 Prion
• WHAT IS MICROBIOLOGY?
• WHAT IS MEDICAL MICROBIOLOGY?
• WHO STUDIES MEDICAL MICROBIOLOGY?
• WHY DO WE STUDY IT?
• WHERE DO WE STUDY IT?
• WHAT KNOWLEDGE WILL A STUDENT GAIN
FROM THIS COURSE?
• HOW DO WE STUDY IT?
Textbook: Jawetz Melnick & Adelbergs
Medical Microbiology 26th
How to use the textbook, it is not a easy book for beginner.
Attending the lectures, and on time!
Follow the lecture notes and keywords, read the textbook,
and add more information to you notebook;
Pay attention to the summary or objectives in the end of
each chapter, and go through the review questions
If there any questions, just ask;
You may “catch” me in the lab after 4:00 pm at weekday or
weekends morning (54237524) ; dqu@shmu.edu.cn
Homework: at the end of lecture ppt. or on elearning
Students: hand out on elearning in 2 weeks after lecture
(deadline set on the elearning), email not acceptable
Teacher: Feedback in 2 weeks (after the deadline for
handing the homework) 4
Micro-organisms (or microbes for short) affect
every aspect of life on the earth
can be friend or foe
– In all environments
– Many beneficial aspects
– Related to life processes
(food web, nutrient cycling…)
– Only a minority are pathogenic， majority are
completely harmless
– Most of our problems are caused by microbes
We couldn’t live without them, but they could
live without us
 We are not alone
The Human Microbiome
project: -DIVERSE

http://pinter
est.com/as
wimm/micro
biome/
Healthy Soil Microbes, Healthy People
 external auditory canal

small intestine
 10<1-3
105-6
109
Human body
102 – 1013 cells
– 1014 bacteria

106-7 103-6

105-7
103

109-11
Different bacteria inhabit in different tissues

Bacteria Tissure
Corynebacterium diphtheriae Throat

Streptococcus mutans Tooth surfaces

Streptococcus salivarius Tongue surfaces

Small intestine
Escherichia coli
epithelium

Staphylococcus aureus Nasal membranes

Staphylococcus epidermidis Skin

 Microorganisms can be friend or foe

Microbes
interacting with
hosts

Microbes influence
the evolution of
http://pinterest.com/aswimm/microbiome/ hosts
Symbiosis
Commensalism
Parasitism
 Types of symbiotic
microbe-host relationships
Mutualism * Commensalism * Parasitism

Benefit to the bacteria: have a place to

survive and multiply with nutrients
Benefits to the human:
 Bacteria may produce vitamins (B and
K), and break down food that host cant
normally digest.
 Normal flora protect host against
infection by pathogenic organisms
 Types of symbiotic
microbe-host relationships

Mutualism * Commensalism * Parasitism

– Harm to the host from

One partner in the invasion by a pathogen.
relationship benefits.
– Cost to the host can vary
The other neither
from slight to fatal.
benefits nor is harmed.
–Infectious disease

Image: Blood Agar showing Beta hemolysis, T. Port.

 Microbes and humans

Very few microbes are

always pathogenic

Many microbes are

potentially pathogenic

Most microbes are

never pathogenic
The iceberg concept of infectious disease

Poliomyelitis in a child Classical

clinical disease
0.1-1% of infections are
clinically apparent
Less severe
disease
Rubella
50% of infections are
clinically apparent
Asymptomatic
Spectrum of infection
virulence

Rabies
100% of infections
are clinically apparent
 Impact of infectious disease

Average life span:

- Bronze age 26 yrs

- Medieval Europe (400 – 1500 ad) 30 yrs

- Early 20th century 50 – 64 yrs
- Now world average 67.2 years (USA., 78.1)

From the Virtual Microbiology Classroom on ScienceProfOnline.com

Impact of infectious disease

Bubonic Plague
Black Plague & Black Death
Caused by bacteria
Yersenia pestis.
Several pandemics of
plague have occurred
throughout history.
50 million deaths between
1656 Physician attire years 1346 –1350.
for protection from
the Bubonic plague Nearly 1/2 of Europe
(Black death). perished in this plague
Black Death illustration, Toggenburg Bible (1411);
Black Plague Physician Attire, History of Medicine,
Paul Furst
 Bubonic Plague

Images: Worldwide distribution of plague 1998,

CDC; Waste in open market, frabood; Brown rat,
National Park Service; Scanning electron
micrograph of flea, CDC
 Impact of infectious disease

Smallpox ( Variola virus)

Caused two airborne virus variants,
Variola major and Variola minor.
Deadly disease that, in survivors, can
cause disfigurement and blindness.
Approx 500 million deaths worldwide
in the 20th century.
Eradicated in 1979 though
widespread vaccination.
Now still possible weapon of
bioterrorism.
Images: Girl with smallpox, James Hicks, CDC; Electron micrograph
of smallpox virus, Magnus Manske; Smallpox vs. Chickenpox
 Impact of infectious disease

Influenza
Influenza caused by RNA viruses
(Orthomyxoviridae).
Spanish flu pandemic 1918;
more than 50 million deaths.
In the U.S. seasonal flu kills
thousands of people every year
(mainly very young and old).
pandemic influenza
seasonal flu
Images: Influenza virus, Cynthia Goldsmith; Walter Reed
Hospital Spanish Flu Ward, by Harris & Ewing via Library of
Congress; Symptoms of influenza, Mikael Häggström
 Impact of infectious disease
AIDS (HIV)

 Acquired immune deficiency

syndrome (AIDS).
 Caused by HIV (human
immunodeficiency virus), a
retrovirus that infects T-cells of the
immune system.
 More than 25 million people have
died from since it was recognized
in 1981.
 With anti-retroviral drug therapy,
more, and more people are living
with aids.

Images: Aids viruses budding off a lymphocyte, C. Goldsmith,

CDC; Main symptoms of Aids, Mikael Haggstrom
 Impact of infectious disease

HBV
 Hepatitis B caused by
hepatitis B virus (HBV).
 Virus transmitted by
exposure to infectious blood
or body fluids.
 Risk of HBV transmission
from carrier 10 – 35%.
 Health care workers high risk group.
 HBV is 50 to 100 times more infectious than HIV.
 HBV infection may be either acute or
 Get vaccinated!
Images HBV virions, PHIL #5631; HBV prevalence 2005,
 Impact of infectious disease

Ebola first appeared in 1976 in 2 simultaneous outbreaks, in

Nzara, Sudan, and in Yambuku, Democratic Republic of
Congo.
Ebola virus disease (EVD), formerly known as Ebola
haemorrhagic fever, is a severe, often fatal illness in
humans.
Filoviruses
Ebola Virus Named after a river in the Republic of Congo
(Formerly Zaire)
318 human cases, 88% mortality
Four subtypes
 Natural Habitat = Africa
Sudan
• Zaire (Democratic
Republic of the Congo)
– Ebola-Zaire
• Sudan
– Ebola-Sudan
• Gabon
Ivory Coast
• Ivory Coast Uganda
Gabon
– Ebola-Cote d’Ivoire
Congo
• Uganda
• Republic of the Congo
(not the DRC)
DRC
EVD fatal in humans and non-human primates, outbreaks
have a case fatality rate of up to 90%.
EVD outbreaks occur primarily in remote villages in Central
and West Africa, near tropical rainforests.
The virus is transmitted to people from wild animals and
spreads in the human population through human-to-human
transmission, by close personal contact in hospital setting
(amplification)
Fruit bats of the Pteropodidae family are considered to be the
natural host of the Ebola virus.
Severely ill patients require intensive supportive care. No
licensed specific treatment or vaccine is available for use in
people or animals.
 Impact of infectious disease

Ebloa 2014
1st Ebola outbreak in West
Africa
• 4 countries:
Guinea
Sierra Leone
Liberia
Nigeria
• Ebola is fatal in 55-60% of
cases reported in this
outbreak.
Human to human
In the 2014 Ebola outbreak, nearly all of the
cases of EVD are a result of human-to-human
transmission.
2 to 21 days
The incubation period from time of infection to
symptoms is 2 to 21 days.
47% survive
In this Ebola outbreak, the survival rate has been
higher than previous outbreaks.
http://www.who.int/csr/disease/ebola/en/
Total death from EVD (7 September 2014) : 2218/4366, ~51%
among them heath workers: 144/301, ~48%
Dr Sheik Humarr Khan die of EVD
Aleading doctor who risked his own life to
treat dozens of Ebola patients, as a
national hero for treating the disease in
Sierra Leone
He had been hospitalized in quarantine.
Health workers have been especially
vulnerable to contracting Ebola, which is USA
spread through bodily fluids such as saliva, 4 doctors
sweat, blood and urine. have been
Two US health workers are currently infected
hospitalized with Ebola in neighboring
Liberia.
10 September, 2014
Dr Roberto Morales Ojeda, Minister of Public Health, has
announced that Cuba will send a medical team of 165
people to Sierra Leone to help in the frontline in the Ebola
response efforts, on a six month rotation starting early
October
The Cuban team consists of 100 nurses, 50 doctors, 3
epidemiologists, 3 intensive care specialists, 3 infection
control specialist nurses and 5 social mobilization officers,
all overseen by epidemiologist Dr Jorge Juan Delgado
Bustillo
 Medical microbiology
Study of causative agents of human infectious diseases
and reactions to the infections.
Etiology, pathogenesis, laboratory diagnosis, specific
treatment and control of infection (immunization).
 EUKARYOTES
-Fungi
-Plants
-Animals
PROKARYOTES
Virus
Prions
BACTERIA ARCHAEA
真细菌 古细菌 Eubacter-"True" bacteria
-human pathogens
Chapter 3, p.43 -clinical or environmental
-one kingdom
Archaea
-Environmental organisms41
Biologic Relationships of Pathogenic Microorganisms

Based on rRNA data

Figure 3-3 in Chapter 3, p.48

Why no Virus in the “tree”?
 Biologic Relationships of Pathogenic Microorganisms

Kingdom Pathogenic Type of Known Estimated

Microorganis Cells species total
ms species
Animal Helminths Eukaryotic
Plant None Eukaryotic
Protist Protozoa Eukaryotic
Fungi Eukaryotic 69,000 1,500,000
Prokaryote Bacteria Prokaryotic 4760 40,000
Not cell Viruses Noncellular 5,000 130,000
Viroids Noncellular
Prions Noncellular
 Comparison of Medical Important Microbes
Characteristic Viruses Bacteria Fungi
Cells No Yes Yes
Size 0.02–0.2 1–5 3–10 (yeasts)
diameter (mm)
Nucleic acid DNA or RNA DNA and RNA DNA and RNA
Chromosome No One More than one
Type of None Prokaryotic, no Eukaryotic,with
nucleus nuclear nuclear
membrane membrane
Ribosomes Absent 70S 80S
Mitochondria Absent Absent Present

Nature of Protein capsid Rigid cell wall Rigid cell wall

outer surface and lipoprotein containing containing chitin
envelope peptidoglycan
Motility None Some None
Method of Not binary fission Binary fission Budding or
replication mitosis
 Large subunit Small subunit
Type Size
(rRNAs) (rRNA)
50S 30S
Prokaryotic 70S 5S : 120 nt, 16S : 1542 nt
23S : 2906 nt
60S 40S
5S : 121 nt
Eukaryotic 80S
5.8S : 156 nt 18S : 1869 nt
28S : 5070 nt)
Multiple sequences of 16S rRNA can exist within a
single bacterium, highly conserved between different
species of bacteria.
16S rRNA gene sequences contain hypervariable regions
that can provide species-specific signature sequences
useful for bacterial identification
Ribosomal Database Project, NCBI
Medical Microbes are diverse
-In genomes, in phenotypes, in metabolism…
Microbes cause disease in human:
 Eukaryocytes : Fungi
 Prokaryocytes: Bacteria
Major categories and Group of Bacteria:
common bacteria, Mycoplasma, Chlamydia,
Spirochetes, Rickettsia, Actinomycetes
 Viruses
 Prions
 Major Categories of Bacteria
Characte Bacteria Spiroche Mycopla Chlamy Ricketts
ristic tes sma dia ia
Size 0.5~3.0 6~20 0.2~0.3 0.2~0.4 0.3~0.5
(mm)
Cell wall yes yes No yes yes
Composit Cell wall Outer Similar to Share
ions of with membrane G- common
peptidoglyc + Sterol in bacteria antigen
CW an peptidoglyc the cell with B.
an membrane proteus

Multiplica Binary Binary Binary Intracell Intracell

tion fission fission fission ular, ular,
Binary Binary
fission fission
Filtration - - + + +
 Viruses- no cellular structure, contain only either
RNA or DNA as genome , rely on enzymes of hosts,
can only replicate in cells

Electron microscope
Microscope Scan electron microscope
Confocal microscope
 Taxonomic Ranks
Bacillus
Formal Rank Example (E. coli)
B. anthracis
Kingdom Prokaryotae
Clostridium tetani Division Gracilicutes
C. Tetani Class Scotobacteria
E. coli Order Eubacteriales
Family Enterobacteriaceae
Capital letter Genus Escherichia
small letter Species coli
Subtype Escherichia coli O157: H7
Taxonomy  Family: related genera
 Classification  Genus: related species
 Species: related strains
 Identification
 Type: sub-set of species
 Nomenclature  Strain: one single isolate 49
Bacteria classification or identification
Growth
Morphology
Biochemical test
-Chemical Fingerprinting
Immunological test
-Serotyping
Genetic analysis Virus classification different
- Genotyping
- 16S ribosomal RNA
 Medical microbiology
• Bacteriology – the science of bacteria, the causative
agents of a member of infectious diseases.
• Virology – the science of viruses, non-cellular living
systems, capable of causing infectious diseases in man.
• Mycology – the study of fungi pathogenic for man.
• Anti-infection Immunology – the science which
concerned with mechanisms of body protection against
pathogenic microorganisms and foreign cells and
substances.
Everyone has being
infected experience
 Microbes Infections in
human

Clinical laboratory Internal Medicine

Pathology Lemology（Infectious diseases）
Immunology Pediatrics
Pharmcology Gynecology
Vaccinology Obstetrics
Biotechnology Urology
Research Surgery
Microbial Forensics Otorhinolaryngology
… General medical practitioner
…
 Selected Novel Prizes in Physiology or Medicine
1901* von Behring Diphtheria antitoxin
1902 Ross Malaria transmission
1905 Koch TB bacterium
1908 Metchnikoff Phagocytes
1945 Fleming, Chain, Florey Penicillin
1952 Waksman Streptomycin
1969 Delbrück, Hershey, Luria Viral replication
1975 Baltimore, Dulbecco, Tumor virus and RTase
Temin
1987 Tonegawa Antibody genetics
1997 Prusiner Prions
2005 Marshall, Warren Helicobacter and ulcers

2008 Barré-Sinoussi and HIV

Luc Montagnier
Hausen Papilloma and viruses

* The first Nobel Prize in Physiology or Medicine.

 Where we study the Medical Microbiology
 Class room
 Medical Microbiogical Laboratory
 Clinics- self learning

Lectures, experiments,
discussion and visiting
hospital laboratory http://www.udel.edu/mls/micro-lab.htm
Where the pathogenic microbes are from?

 Reservoir: source of organisms

– Humans
– Animals (zoonoses)
– Environment
 Contact
– direct
– indirect
 Droplet -aerosol
 Vehicle
 Vector
Emerging
Infectious
Disease
http://www.who.int/topics/
emerging_diseases/en/

http://www.cdc.gov/
 Nosocomial
Infections

• Hospital-acquired
• 5-15% of patients
acquire infection

Patients Doctors/Nurse/Staffs
To patients Equipment…
 Washing hands

Global
Handwashing Day
2008-

•A lab coat or a
large Lab shirt to
cover yourself
•NO eating… in the
laboratory
•Safety
 “My 5 Moments for Hand Hygiene”

Sax H, Allegranzi B, Uçkay I, Larson E, Boyce J, Pittet D. J Hosp Infect 2007;67:9-21

The Keys to Learn Medical Microbiology
Biological characteristics ( morphology,
structure, metabolism, genetics, proteins)
Related to pathogenesis
Related to immune responses
Useful for diagnosis
Useful for prevention
Useful for treatment
(Useful for other purposes- Energy production, Oil
clearance ,excellent model for study of life sciences)
Final grades determined according to the ratios in the
following：
Lecture exam-60% (midterm 20%, final 40%）;
Experiment exam-20%;
Attendance -10% (leave needed if you can not attend a
lecture)
Homework-10%（each lecture gives 2-3 questions,
students choose some of those as homework, submit the
homework to elearning before the deadline. Total 10 for the
course)
http://elearning.fudan.edu.cn/portal
http://jpkc.fudan.edu.cn/s/328/main.htm
http://www.accessmedicine.com/textbooks.aspx

http://www.microbiologyonline.org.uk/home (SGM)
• WHAT IS MICROBIOLOGY?
• WHAT IS MEDICAL MICROBIOLOGY?
• WHO STUDIES MEDICAL MICROBIOLOGY?
• WHY DO WE STUDY IT?
• WHERE DO WE STUDY IT?
• WHAT KNOWLEDGE WILL A STUDENT GAIN
FROM THIS COURSE?
• HOW DO WE STUDY IT?
Textbook: Jawetz Melnick & Adelbergs
Medical Microbiology 26th
 Comparison of Medical Important Microbes
Characteristic Viruses Bacteria Fungi
Cells No Yes Yes
Size 0.02–0.2 1–5 3–10 (yeasts)
diameter (mm)
Nucleic acid DNA or RNA DNA and RNA DNA and RNA
Chromosome No One More than one
Type of None Prokaryotic, no Eukaryotic,with
nucleus nuclear nuclear
membrane membrane
Ribosomes Absent 70S 80S
Mitochondria Absent Absent Present

Nature of Protein capsid Rigid cell wall Rigid cell wall

outer surface and lipoprotein containing containing chitin
envelope peptidoglycan
Motility None Some None
Method of Not binary fission Binary fission Budding or
replication mitosis
 Major Categories of Bacteria
Characte Bacteria Spiroche Mycopla Chlamy Ricketts
ristic tes sma dia ia
Size 0.5~3.0 6~20 0.2~0.3 0.2~0.4 0.3~0.5
(mm)
Cell wall yes yes No yes yes
Composit Cell wall Outer Similar to Share
ions of with membrane G- common
peptidoglyc + Sterol in bacteria antigen
CW an peptidoglyc the cell with B.
an membrane proteus

Multiplica Binary Binary Binary Intracell Intracell

tion fission fission fission ular, ular,
Binary Binary
fission fission
Filtration - - + + +