Medical micro biology Shanghai Medical College of Fudan University Lectures Content Key words Key points questions History of Microbiology commensal microbes 1.WHY?I need to study Milestones in Microbiology pathogenic microbes Medical Microbiology Recent progress in Microbiology plasmids 2. HOW? To stud Emerging and re-emerging infectious diseases genetic exchanges 3.WhaT are those that pathogenic islands Synthetic genomics Phenotype properties Bacteria Rickettsia, Chlamydia
1 Medical Microbiology Shanghai Medical College of Fudan University Lectures Content Key words Key points & questions Introduction History of Microbiology Milestones in Microbiology Recent progress in Microbiology Emerging and re-emerging infectious diseases commensal microbes pathogenic microbes plasmids genetic exchanges pathogenic islands Synthetic genomics Self replication Phenotype properties Prokaryote Bacteria Viruses Fungi Prions Rickettsia, Chlamydia, Mycoplasma, Spirochetes , Actimycetes 1.WHY? I need to study Medical Microbiology 2.HOW? To study 3.WHAT ? are those that I should remember?
2. Bacterial Structure 1. Basics of bacterial cell wall structures and properties associated Gram+/- Related with d iseases or clinic Metabolism Growth with bacterial cell walls( Gram positive/negative cell Questions staining, Peptidoglycan, LPS, pathogenesis, and targets of Peptidoglycan Summary the antibiotics) differences between the cell 2. Structures of the bacterial cell and the genetic makeup of bacteria mucopeptide)Outer wall of G+bacteria and (Ribosome, Plasmid, Chromosome, target of antibiotics, roles in membrane(LPS) G-bacteria(related with athogenesis or drug resistance) Cell membrane medical practice) 3. Morphology of bacteria and the versatility of bacteria(in clinical Spheroplast/protoplast 2. Why penicillin and diagnosis) L form lysozome have less effect on 4. Bacterial appendages, bacterial spores, capsules, etc, and their Flagella(Chemotaxis)G-bacteria related with clinic practice Pili(fimbriae) 3. Spore germination 5. Techniques to study morphology of bacteria Bacterial growth, Capsule(slime layer, activation conditions(related survival and death, cultivation of bacteria, growth curve, bacterial glycocalyx) with medical practice metabolism. classification of bacteria Clostridium tetani-tetenus Growth curve Explain which bacterial structures can be as an antibiotics target 5. Why a doctor should know the growth curve of
2 2.Bacterial Structure, Metabolism & Growth 1. Basics of bacterial cell wall structures and properties associated 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. Gram +/- cell wall, Peptidoglycan (murein, mucopeptide) Outer membrane (LPS ) Cell membrane Spheroplast/protoplast L form Flagella (Chemotaxis) Pili (fimbriae) Capsule (slime layer, glycocalyx) Spore (resistant) Growth curve Related with diseases or clinic Questions: 1. Summary the differences between the cell wall of G+bacteria and G-bacteria (related with medical practice) 2. Why penicillin and lysozame have less effect on G- bacteria? 3. Spore germination activation conditions (related with medical practice, Clostridium tetani -tetenus ) 4. Explain which bacterial structures can be as an antibiotics target. 5. Why a doctor should know the growth curve of bacteria?
3. Bacterial Heredity 1. Genetic material of bacteria( Chromosome, plasmid, transposable Chromsome, Plasmid &variation element, integron and phage genome) Transposable Genetic 1. Does the phenotype of an 2. Bacterial phages, virulent phage and lysogenic phage Elements organism automatically 3. Mechanisms of transfer and recombination of bacterial genes Phage change when a change in genotype occurs? Why or 4. The significance of bacterial genetic variation(in drug resistance, -virulent phage o A (transformation, transduction, conjugation and lysogenic Lysophage(temperate) why not? conversion), gene mutation prophage, lysogeny 2. Can phenotype change pathogenesis or virulence and variation, diagnosis, and without a change in vaccination), and manipulation of cloned DNA Transformation 5. Sterilization and disinfection(concepts and methods discuss inTransduction he experiment course General transduction (specific) transduction answer Conjugation 3. List the biological F factor, Hfr, R significances of gene transfer in bacteria
3 3. Bacterial Heredity &Variation 1. Genetic material of bacteria (Chromosome, plasmid, transposable 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
4. Bacterial Infection 1. Normal human microbiota(Role of the resident microbiota, and Microbiota Pathogenesis locations in the human body) Opportunistic 1. How should we identify a 2. Virulence of bacteria, bacterial virulence factors and their pathogen Nosocomial pathogen responsible for an regulation, (exotoxin, endotoxin, and their contribution to infections Opportunistic infection 2. Summary the differences 3. Infection process(development, and outcomes Virulence of bacteria between the endotoxins and 4. Modes of infectious d isease transmission Adhesion 5. Nosocomial infections and their prevention Penetration 6. Bacteria biofilm formation and biofilm associated diseases Invasiveness/spread 3. How we control nosocomial infections? Exotoxin Endotoxin Do you know the difference the terms Compromised host following. bacteremia Bacterial biofilm Septicemia, Pyemia, koch’ s postulates Toxemia, Endotoxemia. Why Transmission we should understand it? Outbreak, Epidemic Disease/treatment/prevention Pandemic 5. Why there are no effective antibiotics for biofilm associated diseases? Then
4 4.Bacterial Infection & Pathogenesis 1．Normal human microbiota (Role of the resident microbiota, and 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?
Human Immune Immunity and immune responses against bacterial infection Extracelluarphathogen1.compareanti-b Response to bacterial 2. Mechanisms of innate immunity (barriers, phagocytes, Intracelluar pathogen Infections, Control of complement system etc. Active immunization Immune response to bacterial diseases 3. Mechanisms of specific host defense (humoral immunity, Passive immunization exocellular/ or intracellular ell-mediadted immunity, their activities on exocellular/or intracellular bacterial infection hy specific IgM/not lg 4. Prevention of bacterial infection(active immunization, vacc ines can be used as early and passive immunization diagnosis of an infection? 3. How the knowledge would help you in clinical
5 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?
6. Antimicrobial 1. Antimicrobial Chemotherapies and their targets Antibiotic 2. Drug resistance, drug-bacteria relationship, clinical implications, 1. List the bacteria targets Laboratory d and prevention Selective toxicity with the responsive 3. Diagnostic medical microbiology(collect samples, culture, Bactericidal identification, rapid diagnosis/ immunologic /or molecular Bacteriostatic 2. List antibiotic resistant in 4. Biosafety in the medical microbiology laboratory(discuss in the Drug resistance experiment course?) 3. Why the sample collection is very important in the diagnostic medical microbiology? Is it related 4. Why biosafety procedures micro ory or 7. Cocci 1. The pathogenic substances of Staphylococcus aureus and the diseases CNS How to caused by Staphylococcus aureus 2. Classification of streptococci xigenic disease non- 3. The pathogenic substances of group A streptococcus; the pyogenic and Alpha/Beta/Gamma Describe the virulence factors of non-pyogenic infections caused by group A streptococcus hemolysis aphylococcus 4. The biological characteristics, pathogenicity and immunity of ASo test and streptococcus
6 6. Antimicrobial Chemotherapy & Laboratory Diagnosis, bio-safety 1. Antimicrobial Chemotherapies and their targets 2. Drug resistance, drug-bacteria relationship, clinical implications, and prevention 3. Diagnostic medical microbiology (collect samples, culture, identification, rapid diagnosis/ immunologic /or molecular diagnostic tests ) 4. 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
Enterobacteriaceae: 1. General characterization and class ification of lactose ferment pattem 1. Take the EHEC infection as a General introduction, Enterobacteriaceae Differentiate media, Motile test, example, to clarify how to Escherichia coli &2. Escherichia coli iagnose infectious disease? Shigella (I)Diseases induced by Escherichia coli, including H antigen, How do the Shigella toxins pathogenesis and Clinical Findings I antigen, play a role in diarrhea (2)Diagnostic laboratory tests for Escherichia coli 157: H7, development? EPEC-EHEC Why the number of E coli can ()Treatment, Epidemiology, Prevention and Control of ETEC(LT &ST) be used as a standard for measure Enterobacteriaceae- associated diseases AEC, Shiga toxin, Shigella f water? 3. Shigella (1)Serological classification of Shigella, pathogenesis and (2)Diagnostic laboratory tests and immunity of Shigella-associated diseases reatment, Epidemiology, Prevention and Control of the
7 8 Enterobacteriaceae: General introduction, Escherichia coli & Shigella 1.General characterization and classification of Enterobacteriaceae 2. Escherichia coli (1) Diseases induced by Escherichia coli, including pathogenesis and Clinical Findings (2) Diagnostic laboratory tests for Escherichia coli -associated diseases (3) Treatment, Epidemiology, Prevention and Control of Enterobacteriaceae- associated diseases 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 Lactose ferment pattern, Differentiate media, Motile test, O antigen H antigen, Vi antigen, O157:H7, EPEC,EHEC, ETEC(LT &ST) , EAEC, Shiga toxin, 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?
9 Enterobacteriacea: 1. Salmonella salmonella. 1. How to control the salmonella ibrios,()Pathogenesis and clinical finding for the disease Enteric Fever, infection? Campylobacte induced by salmonella Widal test, TSI agar. 2. Please describe the biological elicobacter (2)Diagnostic laboratory tests for the diseases caused by elicobacter species characters of helicobacter Salmonella, including bacteriologic methods for one (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 usehold pets) 2. Vibrios (1)Pathogenesis of the diseases induced by vibrio cholerae and the immunity (brio 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 (2)Pathogenesis and pathology of the Helicobacter species-associated diseases (3)Diagnostic laboratory tests for the diseases induced by Helicobacter species
8 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
0. Mycobacterium 1. Mycobacterium tuberculosis mycobacterium tuberculosis 1. Selection is the key for TB (I)The main biological characteristics of M tuberculosis BCG (2)Pathogenesis of M tuberculosis, Koch's phenomenon PPD selective steps/conditions for TI 3)Diagnosis of M. tuberculosis infection, treatment and prevention Lowenstein-Jensen Med ia 2. What is the difference 2. Mycobacterium leprae leprosy iehl Neelsen Stain(Acid-Fast) between drug tolerance and drug-resistency? In pinion, what might be the best molecular based methods(see chapter 48 for the methods) for TB-detection? 11. Anaerobic Bacteria 1. The definition and characters of anaerobes What clues/symptoms are 2. Clostridum, non-spore forming anaerobes nsidered as passible anaerobic (1)Clostridum botulinum, pathogenesis of botulism and the Characteristics of anaerobic infections, infections? botulinum toxin 2. What is the general principle or (2)Clostridum tetani, pathogenesis of tetanus and the tetanospasmin Toxins:botulinum,tetanospasmin eatment of anaerobic fections? Select on bacterium covered in (4)Clostridum difficile, antibiotic-associated diarrhea(AAD)and his lecture. summarize the elated knowledge you have 3. Infection caused by the non-spore forming anaerobe, Bacteroides
9 10. Mycobacterium 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. 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? 11. Anaerobic Bacteria 1. The definition and characters of anaerobes 2. Clostridum , non-spore forming anaerobes (1) Clostridum botulinum, pathogenesis of botulism and the botulinum toxin (2) Clostridum tetani, pathogenesis of tetanus and the 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 anaerobe, Characteristics of anaerobic infections, Toxins: botulinum, tetanospasmin 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
Biological characters, infection and immunity, pathogenesis and tic bacteria, 1. Select one zoonotic bacterium diagnosis, treatment and prevention of following bacteria: (undulant feve ered in this lecture racis,Leginellae1. Brucella, the transimmison nad pathogenesis of brucellosis ague(black death ), anthrax toxin, X the related knowled s 3. Bacillus anthracis. the pathogenesis of anthrax paroxysmal stage of pertussis, por 5. Bordetella and whooping cough(pertussis) have learned on one of the 6. Leginellae pneumophila and Legionnaires disease following bacteria: H. Influenza, B. pertussis, and L pneumophila
10 12. H.influenza, Yersinia, Bordetella& Brucella, B.anthracis, Leginellae Biological characters, infection and immunity, pathogenesis and diagnosis, treatment and prevention of following bacteria: 1. Brucella, the transimmison nad pathogenesis of brucellosis 2. Yersinia pestis and plague 3. Bacillus anthracis, the pathogenesis of anthrax 4. Haemophilus influenzae and related disease 5. Bordetella and whooping cough (pertussis) 6. Leginellae pneumophila and Legionnaire's disease Zoonotic bacteria, brucellosis (undulant fever), plague (black death), anthrax toxin, X and V factor, the catarrhal and paroxysmal stage of pertussis, pontiac fever 1.Select one zoonotic bacterium covered in this lecture, summarize the related knowledge you have learned. 2.Summarize the knowledge you have learned on one of the following bacteria: H. Influenza, B. pertussis, and L. pneumophila