Medical Microbiology
Shanghai Medical College of Fudan University
Lectures
Introduction
Content
History of Microbiology
Milestones in Microbiology
Recent progress in Microbiology
Emerging and re-emerging infectious diseases
Key words
Key points & questions
commensal microbes
1.WHY? I need to study
pathogenic microbes
Medical Microbiology
plasmids
2.HOW? To study
genetic exchanges
3.WHAT ? are those that I
pathogenic islands
should remember?
Synthetic genomics
Self replication
Phenotype properties
Prokaryote
Bacteria
Viruses
Fungi
Prions
Rickettsia, Chlamydia,
Mycoplasma,
Spirochetes , Actimycetes
1
2.Bacterial Structure, 1. Basics of bacterial cell wall structures and properties associated
Metabolism & Growth
with bacterial cell walls (Gram positive/negative cell wall,
staining, Peptidoglycan, LPS, pathogenesis, and targets of
antibiotics)
2. Structures of the bacterial cell and the genetic makeup of bacteria
(Ribosome, Plasmid, Chromosome, target of antibiotics, roles in
pathogenesis or drug resistance)
3. Morphology of bacteria and the versatility of bacteria (in clinical
diagnosis)
4. Bacterial appendages, bacterial spores, capsules, etc., and their
related with clinic practice.
5. Techniques to study morphology of bacteria Bacterial growth,
survival and death, cultivation of bacteria, growth curve, bacterial
metabolism, classification of bacteria.
Related with diseases or clinic
Gram +/cell wall,
Questions:
1.
Summary the
Peptidoglycan
(murein,
differences between the cell
wall of G+bacteria and
mucopeptide) Outer
G-bacteria (related with
membrane (LPS )
Cell membrane
medical practice)
Why penicillin and
Spheroplast/protoplast 2.
lysozame have less effect on
L form
G- bacteria?
Flagella (Chemotaxis)
3.
Spore germination
Pili (fimbriae)
activation conditions (related
Capsule (slime layer,
with medical practice,
glycocalyx)
Clostridium tetani -tetenus )
Spore (resistant)
4.
Explain which bacterial
Growth curve
structures can be as an
antibiotics target.
5.
Why a doctor should
know the growth curve of
bacteria?
2
3. Bacterial Heredity 1. Genetic material of bacteria (Chromosome, plasmid, transposable
&Variation
element, integron and phage genome).
2. Bacterial phages, virulent phage and lysogenic phage
3. Mechanisms of transfer and recombination of bacterial genes
(transformation, transduction, conjugation and lysogenic
conversion); gene mutation.
4. The significance of bacterial genetic variation (in drug resistance,
pathogenesis or virulence and variation, diagnosis, and
vaccination), and manipulation of cloned DNA.
5. Sterilization and disinfection (concepts and methods discuss in
the experiment course)
Chromsome, Plasmid
Transposable Genetic
Elements
Phage
-Lysophage (temperate)
prophage, lysogeny
-virulent phage
Gene transfer:
Transformation
Transduction
General transduction
Lysogenic（specific）
transduction
Conjugation
F factor，Hfr， R
plasmid
1. Does the phenotype of an
organism automatically
change when a change in
genotype occurs? Why or
why not?
2. Can phenotype change
without a change in
genotype?
In both cases, give some
examples to support your
answer.
3. List the biological
significances of gene transfer
in bacteria.
3
4.Bacterial Infection & 1．Normal human microbiota (Role of the resident microbiota, and
Pathogenesis
locations in the human body)
2．Virulence of bacteria, bacterial virulence factors and their
regulation , (exotoxin, endotoxin, and their contribution to
pathogenesis)
3．Infection process (development, and outcomes)
4．Modes of infectious disease transmission
5．Nosocomial infections and their prevention
6．Bacteria biofilm formation and biofilm associated diseases
Microbiota
Opportunistic
pathogen Nosocomial
infections
Opportunistic infection
Virulence of bacteria
Adhesion
Penetration
Invasiveness/spread
Exotoxin
Endotoxin
Carrier
Compromised host
Bacterial biofilm
Koch’s postulates
Transmission
Outbreak, Epidemic,
Pandemic
1. How should we identify a
pathogen responsible for an
infectious disease (Koch’s )
2. Summary the differences
between the endotoxins and
exotoxins
3.
How we control
nosocomial infections?
4. Do you know the
difference the terms as
following: Bacteremia ,
Septicemia, Pyemia,
Toxemia, Endotoxemia. Why
we should understand it?
Disease/treatment/prevention
5. Why there are no effective
antibiotics for biofilm
associated diseases? Then
what we should do?
4
5.Human Immune
Response to bacterial
Infections, Control of
bacterial diseases
1. Immunity and immune responses against bacterial infection
2. Mechanisms of innate immunity (barriers, phagocytes,
complement system etc.)
3. Mechanisms of specific host defense (humoral immunity,
cell-mediadted immunity, their activities on exocellular/ or
intracellular bacterial infection.
4. Prevention of bacterial infection (active immunization, vaccines,
and passive immunization)
Extracelluar phathogen
Intracelluar pathogen
Active immunization
Passive immunization
1. Compare anti-bacterial
immune response to
exocellular/ or intracellular
bacteria
2. Why specific IgM /not IgG
can be used as early
diagnosis of an infection?
3. How the knowledge would
help you in clinical
practicing?
5
6. Antimicrobial
1.
Chemotherapy &
2.
Laboratory Diagnosis,
bio-safety
3.
4.
Antimicrobial Chemotherapies and their targets
Drug resistance, drug-bacteria relationship, clinical implications,
and prevention
Diagnostic medical microbiology (collect samples, culture,
identification, rapid diagnosis/ immunologic /or molecular
diagnostic tests )
Biosafety in the medical microbiology laboratory (discuss in the
experiment course?)
Antibiotic
Selective toxicity
Bactericidal
Bacteriostatic
Susceptibility testing
Drug resistance
Penicillinase/beta
lactamase
1. List the bacteria targets
with the responsive
antibiotics.
2. List antibiotic resistant in
clinical implications.
3. Why the sample collection
is very important in the
diagnostic medical
microbiology? Is it related
with doctors?
4. Why biosafety procedures
are important in the medical
microbiology laboratory or in
clinical practicing?
7.Cocci
1. The pathogenic substances of Staphylococcus aureus and the diseases
caused by Staphylococcus aureus
2. Classification of streptococci
3. The pathogenic substances of group A streptococcus; the pyogenic and
non- pyogenic infections caused by group A streptococcus
4. The biological characteristics, pathogenicity and immunity of
meningococcus and gonococcus
CNS,
Pyogenic infections,
Toxigenic disease,
Alpha/Beta/Gamma
hemolysis
ASO test
1.How to distinguish pathogenic
staphylococcus
species from non-pathogenic ones ?
2. Describe the virulence factors of
staphylococcus
and streptococcus
6
8 Enterobacteriaceae:
General introduction,
Escherichia coli &
Shigella
1.General
characterization
and
classification
of Lactose ferment pattern,
Enterobacteriaceae
Differentiate media, Motile test,
O antigen
2. Escherichia coli
(1) Diseases induced by Escherichia coli, including H antigen,
pathogenesis and Clinical Findings
Vi antigen,
(2) Diagnostic laboratory tests for Escherichia coli O157:H7,
-associated diseases
EPEC,EHEC,
(3) Treatment, Epidemiology, Prevention and Control of ETEC(LT &ST) ,
Enterobacteriaceae- associated diseases
EAEC, Shiga toxin, Shigella
3. Shigella
(1) Serological classification of Shigella, pathogenesis and
pathology
(2) Diagnostic laboratory tests and immunity of
Shigella-associated diseases
Treatment, Epidemiology, Prevention and Control of the
diseases induced by Shigella
1.Take the EHEC infection as a
example, to clarify how to
diagnose infectious disease?
2.How do the Shigella toxins
play a role in diarrhea
development?
3.Why the number of E.coli can
be used as a standard for measure
of water?
7
9 Enterobacteriacea:
Samonella, Vibrios,
Campylobacter,
Helicobacter
1. Salmonella
(1) Pathogenesis and clinical finding for the disease
induced by Salmonella
(2) Diagnostic laboratory tests for the diseases caused by
Salmonella, including bacteriologic methods for
isolation of salmonella, serologic methods
(3) Treatment, Epidemiology, Prevention and Control,
including carriers, source of infection (water, milk
and other dairy products, shellfish, dried or frozen
eggs, meats and meat products, animal dye and
household pets)
2. Vibrios
(1) Pathogenesis of the diseases induced by Vibrio
cholerae and the immunity (Vibrio cholerae
enterotoxin and function in the disease)
(2) Diagnostic laboratory tests for the diseases induced by
Vibrio cholerae
(3) Treatment, Epidemiology, Prevention and Control of
the diseases induced by the Vibrio cholerae
3.Helicobacter
(1) The main biological characteristics of the Helicobacter
species
(2) Pathogenesis and pathology of the Helicobacter
species-associated diseases
(3) Diagnostic laboratory tests for the diseases induced by
Helicobacter species
Salmonella,
Enteric Fever,
Widal test, TSI agar,
Helicobacter species
1.How to control the Salmonella
infection?
2.Please describe the biological
characters of Helicobacter
species
8
10. Mycobacterium
11. Anaerobic Bacteria
1. Mycobacterium tuberculosis
(1) The main biological characteristics of M. tuberculosis
(2) Pathogenesis of M. tuberculosis, Koch’s phenomenon
(3) Diagnosis of M. tuberculosis infection, treatment and
prevention
2. Mycobacterium leprae & leprosy
Mycobacterium tuberculosis
BCG
PPD
Tuberculin test
Lowenstein-Jensen Media
Ziehl Neelsen Stain (Acid-Fast)
1. The definition and characters of anaerobes
anaerobe,
2. Clostridum , non-spore forming anaerobes
(1) Clostridum botulinum, pathogenesis of botulism and the Characteristics of anaerobic infections,
botulinum toxin
(2) Clostridum tetani, pathogenesis of tetanus and the tetanospasmin Toxins: botulinum, tetanospasmin
toxin
(3) Clostridum perfringens, the pathogenesis of gas gangrene
(4) Clostridum difficile, antibiotic-associated diarrhea (AAD) and
pseudomembranous colitis
3. Infection caused by the non-spore forming anaerobe, Bacteroides
fragilis
1. Selection is the key for TB
detection. Please outline the
selective steps/conditions for TB
detection.
2.What is the difference
between drug tolerance and
drug-resistency?
3.In your opinion, what might
be the best molecular based
methods (see chapter 48 for the
methods) for TB-detection?
1.What clues/symptoms are
considered as passible anaerobic
infections?
2.What is the general principle on
treatment of anaerobic
infections?
3.Select on bacterium covered in
this lecture, summarize the
related knowledge you have
learned.
9
12. H.influenza, Yersinia, Biological characters, infection and immunity, pathogenesis and Zoonotic bacteria,
1.Select one zoonotic bacterium
Bordetella&
Brucella, diagnosis, treatment and prevention of following bacteria:
brucellosis (undulant fever),
covered in this lecture,
B.anthracis, Leginellae
1. Brucella, the transimmison nad pathogenesis of brucellosis
plague (black death), anthrax toxin, X summarize the related knowledge
2. Yersinia pestis and plague
and V factor, the catarrhal and
you have learned.
3. Bacillus anthracis, the pathogenesis of anthrax
paroxysmal stage of pertussis, pontiac
4. Haemophilus influenzae and related disease
fever
2.Summarize the knowledge you
5. Bordetella and whooping cough (pertussis)
have learned on one of the
6. Leginellae pneumophila and Legionnaire's disease
following bacteria: H.
Influenza, B. pertussis, and L.
pneumophila.
10
Overview: biological characteristics, infection and
immunity, pathogenesis and diagnosis, treatment and
Rickettsiae, Chlamydia & prevention of the microbial infection
Mycoplasma
1. Spirochetes
(1) Leptospira & Leptospiriosis
(2) Treponema pallidum & Syphilis
(3) Borrelia burgdorferi & Lyme disease
1. Rickettsiae & the diseases
2. Chlamydia
(1) Chlamydia trachoma, genital infection and inclusion
conjunctivitis
(2) Chlamydia pneumoniae & respiratory infections
(3) Chlamydia psittaci & psittacosis
3. Actinomycetes, norcardiosis and actinomycetoma
4. Mycoplasma and cell wall-defective bacteria
(1) Mycoplasma pneumoniae & atypical pneumonias
(2) Ureaplasma urealyticum
Cell wall-defective bacteria
14. Viral Classification, 1. General properties of viruses
Structure,
& 2. Principles of virus structure and function (genome,
Multiplication
capsid, envelope)
3. Reaction to physical and chemical agents
4. Viral Multiplication and stages of replication(adhesion,
entry, uncoating, synthesis, assembly and release)
13.
Spirochete,
Spirochete
Treponema pallidum
Congenital Syphilis
Lyme disease
Leptospirosis
Mycoplasma
“Fried egg” colonies
M. pneumoniae
Chlamydia
EB and RB
Rickettsia, Orientia, Ehrlichia,
Anaplasma, Coxiella and Bartonella
1.Make a description of the life
cycle of Chlamydia.
2. What is main characters of
spirochete, Mycoplasma and
Rickettsia?
Virion
Capsid
Helical symmetry
Icosahedral symmetry
Complex symmetry
1.What is a virus?
2.How viruses are classified?
3.What structures do viruses
have?
4.What is an infectious cycle of
a virus?
3. Rickettsia species are carried by
many ticks, fleas, and lice, and cause
diseases. Please make a list to
summarize those species and their
nature vectors.
11
Viral
&Variation
15.
Heredity 1. Genetics of animal viruses
2. Mechanisms of viral gene mutation
3. Defective interfering particle, defective virus
Classification of viruses
Mechanisms of 1.
Viral Pathogenesis and 2.
Human
Immune
Response to
viral 3.
Infections & Control of
viral diseases
16.
Viral infection and transmission
Mechanism of viral pathogenesis：cytopathic effect,
immune pathogenesis and immune escape
Forms of viral infection, viral persistent infection (viral
horizontal transmission and vertical transmission; the
characteristics of chronic virus infection, latent virus
infection, and slow virus infection)
Viral infection and tumors
Mutation (point
mutation/deletion/insertion)
Recombination
Reassortment
Complementation
Interference
Phenotypic mixing
Host-range mutants
Drug-resistant mutants
Primary culture
Continuous cell line
Cytophathic effect (CPE)
Hemagglutination assay
Plaque assay
Defective virus
Human interferons
chronic virus infection
viral persistent infection
Acute infection
chronic infection
slow virus infection
1. How to grow and quantitate
viral particles?
2. How to analyze a viral
sequence?
3. What is virus evolution?
4. What are the forces that
drive virus evolution?
5.What does virus evolution
impact on basic and applied
researches
1.What is viral pathogenesis?
2.What are the common routes
of viral infection?
3.How a viral infection causes
a disease?
4.What are the major antiviral
host defenses?
12
17-1. Laboratory
Diagnosis of Viral
Diseases
1.
2.
3.
4.
5.
River’s postulates and Koch’s postulates;
CPE (Cytopathic effects);
How to determine a patient with
General procedures for viral diagnosis;
Inclusion body; syncytia; PFU;
HIV infection, and monitor the
Animal, eggs, and cells for virus isolation;
TCID50; Hemagglutination;
disease progress?
Basic methods for virus titration
virus interference; neutralization
Basic methods for viral antigen and antibody response and hemagglutination inhibition
detection
assay
17-2. Antiviral therapy 6. Criteria for good antiviral drugs
Antiviral therapy;
- General Principles
7. Antiviral potential targets in the viral life cycle
Nucleoside analogue;
8. Some agents antiviral mechanisms to block virus HAART(highly active
replication;
anti-retroviral therapy);
1.The targets of some important
antiviral agents inhibit virus
replication, such as enfuvirtide,
plecornaril, amantadine,
acyclovir, tamiflu, and interferon.
2.What antiviral drugs could be
applied to treat patients with HIV
infection? Please explain it, and
put forward your idea how to
design new drugs for HIV
treatment.
13
18. Orthomyxovirus
and Paramyxovirus
1. respiratory viruses infection
pandemic/epidemic
2. Orthomyxovirus- influenza virus, morphology in EM, influenza virus
basic structure, viral protein functions
hemagglutinin
3. virus mutant: antigen drift and antigen shift, reassortment neuraminidase
and animal reservoirs
matrix protein
4. mechanism of pandemic and epidemic of influenza
polymerase
5. pathogenesis and clinic
antigenic drift
6. vaccine design for prevention of influenza
antigenic shift
7. paramyxovirus: major properties (ssRNA, one serotype, reassortment
vaccine)
animal reservoirs
1. describe the basic structure and
the function of viral proteins of
influenza virus
2. What are antigen drift and
antigen shift? Try to explain their
molecular mechanism.
3. Why the influenza virus could
cause pandemic/epidemic?
4. To design efficient vaccine to
control the influenza virus, what
aspects should you consider？
14
19.Gastrointestinal
Virus and Rhinovirus
1. Properties and overview of enteroviruses
2. Pathogenicity and immunity of enteroviruses
3. Laboratory diagnosis, prevention & control of
enteroviruses
4. Polioviruses and poliomyelitis
5. Polio vaccines
6. Overview of Coxsackieviruses, Echoviruses and new
enteroviruses
7. General
properties
of
rotaviruses,
Caliciviruses
(norovirus), Enteric adenoviruses and Astroviruses
8. Pathogenicity,
immunity,
laboratory
diagnosis,
treatment and control of rotavirus
Enteroviruses
Poliovirus
poliomyelitis
OPV&IPV
VAPP
EV71
Hand-foot and mouse disease
Viral gastroenteritis Rotavirus
Norovirus
Fecal-oral transmission
Key points:
1. Properties of enteroviruses
2. Pathogenicity and
immunity of enteroviruses
3. Polio vaccines
4. Properties of acute
gastroenteritis-associated
Viruses
5. Pathogenicity and
immunity of rotaviruses
Questions:
1.Why IPV is used in USA
while OPV is used in Africa to
prevent polio now?
2.What are common properties
of these acute
gastroenteritis-associated
viruses?
9. Pathogenicity, treatment and control of norovirus
15
20-21.
viruses
Hepatitis
General concepts for hepatitis
Types of hepatitis
Properties: Structure\ ORF\Replication
Transmission \Epidemiology
Pathogenesis & Immunity
Clinical Features
Laboratory Diagnosis
Treatment \Prevention
Hepatitis virus
open reading frames
HBsAg
HBeAg
HBcAg
Chronic HBV Infection
Primary Hepatocellular Carcinoma
Pre-exposure prophylaxis
Post-exposure prophylaxis
Coinfection
Superinfection
1.What is hepatitis and type of
hepatitis viruses?
2.What are the properties of
HAV-HEV ? How does they
spread?
3.How many ORFs of HBV ?
4.How does the HAV-HEV
cause the liver diseases?
5.How do you interpret
serological lab results for
HBV?
6.How to treat and prevent
HAV-HEV?
7.What is hepatitis and type of
hepatitis viruses?
8.How many ORFs of HAV,
HBV and HCV ?
9.How do you interpret
serological lab results for HAV,
HBV and HCV?
16
22.Retroviruses: HIV &
HTLV
1.
2.
3.
4.
5.
6.
7.
8.
23.Athropod-borne viruses 1.
(Arboviruses) &
2.
Viral hemorrhagic fever
3.
(VHF)
4.
5.
6.
Classification of retroviruses
Properties of HIV: genome, structure, and replication cycle
Origin of HIV and epidemiology of HIV infection
Pathogenesis and pathology of HIV/AIDS
Laboratory diagnosis of HIV infection
Prevention of HIV infection
Treatment of HIV infection/AIDS
Properties of HTLV-1: genome, structure, and replication cycle
Retrovirus,
Human Immunodeficiency Virus
(HIV),
Human T Lymphotropic Virus (HTLV).
1. How does HIV enter into the
target cell and how does T20 block
HIV entry?
General information of arbovirus
Main properties of togaviruses (alphavirus)
Chikungunya caused by alphavirus: epidemiology, symptoms,
diagnosis, treatment, prevention
Main properties of flaviviruses
Dengue fever caused by flavivirus: epidemiology, symptoms,
diagnosis, treatment, prevention
Japanese B Encephalitis caused by flavivirus: epidemiology,
symptoms, diagnosis, treatment, prevention
Arboviruses,
Flaviviridae,
Dengue fever virus,
Japanese B encephalitis virus,
Viral hemorrhagic fever (VHF),
Ebola Virus.
1.How are flaviviruses transmitted
and what is the main disease caused
by the flavivirus infection?
2.Why is Ebola virus the most
dangerous bioterrorism agent and
how to prevent Ebola HF ?
2. How is HIV transmitted sexually
and what is the best way to block
sexual transmission of HI
17
24.Human Herpes Viruses 1.
(HHV) &
Human Papillomavirus
(HPV)
2.
Classification and properties of HHVs; Epidemiology of
genital HPV infection; Pathogenesis; Clinical manifestations
and sequelae; Diagnosis of genital warts and cervical cellular
abnormalities; Treatment; Prevention
Characteristics of HPV; Epidemiology of genital HPV
infection; Pathogenesis; Clinical manifestations and sequelae;
Diagnosis of genital warts and cervical cellular abnormalities;
Treatment; Prevention
Human Herpes Viruses (HHV),
Human Papillomavirus (HPV).
1.How are HSV-1 and HSV-2
transmitted and what are the main
diseases caused by HSV-1 and
HSV-2 infection?
2.Which types of HPV are
considered “high risk” that may
cause pre-cancerous lesions and
lead to cervical cancer?
25．Rabies virus and 1. Slow virus and slow virus infection: slow virus disease caused by Slow virus infection, rabies, negri body, 1.When a person has been bitten by
a possibly rabid animal, what
other viruses & Prion conventional and inconventional viruses, always result in fatal Preexposure and postexposure
encephalitis
Prophylaxis, prion,
2. The prevalence of the rabies. Worldwide and main animals.
3. The characters of the rabies virus. Structure and life cycle and
transmission.
4. The Pathogenesis & Pathology of rabies (The virus replication and
move to CNS, damage to brain, the clinical findings).
5. Preexposure and postexposure Prophylaxis for rabies.(WHO WHO
Recommended Prophylaxis, animal observation )
6. The discovery of prion
7. the characters of prion and prion disease.
should he do? And how to treat the
animals?
2.What are the characters of the
prion and prion disease?
18