微生物大纲

医学微生物学Ⅰ《教学大纲》

一, 课程基本信息

课程名称: 医学微生物学Medical Microbiology

课程号: 50124430

课程类别：基础医学专业课( 供七年制、八年制和基础医学专业学生用)

学时：51 小时学分：3分

二, 教学目的及要求：

医学微生物学是生命科学中的重要学科，是研究病原微生物的形态、结构、生命活动规律以及与机体相互关系的一门重要的基础医学二级学科。为医学生学习临床的感染性疾病、传染病、超敏反应性疾病和肿瘤发生等奠定重要的理论基础。要求学生熟悉微生物学基本理论知识，掌握病原微生物的致病机制及其诊断、预防的主要措施。

三, 教学内容：

医学微生物学是研究病原微生物的形态、结构、生命活动规律以及与机体相互关系的一门重要的基础医学学科，将为临床各科的感染性疾病、传染病、超敏反应性疾病和肿瘤发生等的学习奠定重要的理论基础。同时,还开设了医学微生物学实验课,培养学生的动手能力和分析问题的能力.

本课程主要讲述微生物的基本概念、各类微生物的生物学特性、感染及抗感染免疫的机理、感染性疾病的诊断、预防和治疗原则。针对五年制医学类本科生，着重介绍与人类疾病相关的各种病原微生物（以常见的病原性细菌和病毒为主）的形态结构、培养特性、生化反应、抗原构造、分类、抵抗力等各种生物学特性，致病机理及所致疾病，病原体的分离培养方法及鉴定原则，相关疾病的预防及治疗原则。通过学习，使同学牢固树立“有菌观念”并掌握无菌操作的原则，学会保护自己，也为将来专业课的学习奠定良好的基础。

同时，针对七年制学生的特点，不仅讲述上述知识，而且结合目前临床感染的现状，向同学介绍新现和再现的病原微生物、有关细菌的耐药、微生态平衡与失调、医院内感染及肿瘤相关病毒的知识，以适应七年制教学的要求，拓展学生的视野，提高学生的科学研究能力，培养更高层次的学生。

大纲中的英文黑体字内容,要求掌握; 其他内容要求熟悉.

Medical Microbiology Outline

for 7 and 8 Year’s Students, as well as Basic Medicine Students

Introduction （1 h）

一. Definition, Classification and Characteristics of Microorganisms.

(一) Concept: A kind of microorganism which is small bodies, simple structure, not visible by the naked eyes, visible usually only with light microscope or electromicroscope.

(二) Classification:

1. Non-cellular type: Virus;

2. Prokaryotic group;

3. Eukaryotic group

(三) Characteristics.

二. Relation between Microbes and Human.

Be more beneficial than harmful to Human.

三. Developmental history of microbiology

(一) Experiential period of microbiology

(二) Experimental period of microbiology

1. Morphological period

2. Physiological period:Louis Pasteur; Robert Koch; Iwanovsky

(三) Modern Microbiological period.

Chap.1 Bacterial Biological Properties (1.5 h)

一. Bacterial Size and Morphology

(一) unites of measurement: μm (micron or micrometer); nm;

(二) Basic morphology: Coccus; Bacillus; Spirillar bacterium; (Vibrio; Spirillum;)

(三) Arrangement of bacteria

二. Basic structure of bacteria

(一) Cell Wall

1. Function

2. Composition.

Main component: Peptidoglycan (i.e. mucopeptide)

(1)Backbone: ;（2）Side chain;. （3）(Gly)5 peptide cross-bridge :

(4)Cell Wall Comparison between Gram+ and Gram- bacteria.

(5) L Type bacteria

(二) Cell membrane ; Cytoplasma; Nucleus; Mesosome, Chondroid

三. Special structures of bacteria.

1. Capsule

2. Flagellum

3. Pilus or Fimbriae

4. Spore

四. Examination and Staining:

Simple staining:; Complex staining:

Procedure of Gram’s Stain;Practical Significance of Gram’s stain:

Bacterial Physiology (2.5 h)

一. Chemical Composition and Physical Characteristics of Bacteria. (Self-learning)

二. Growth and Mutiplication of bacteria

(一) Nutritional types of bacteria

(二) Basic requirment of bacterial mutiplication

1.Nutriention: water; carbon source; nitrogen source; inorganic salt; growth factors

(Enzymes, Amino acid…)

2. Optimal pH: 7.8-7.6, 8.5-9 for vibro;

3. Proper Temperature:

4. Definite gaseous: O2, CO2, N2

Anaerobic principles of anaerobes

(1) Do not possess cytochrome oxidase nor cytochrome.

(2) Do not possess hydrogen peroxidase, catalase and superoxide dismutase (SOD).

三. Methods and speed of bacteria growth.

Manner: Simple binary fission

Speed: one generation/15’-20’; one generation/20h. (T.b.) T ypical growth curve of bacteria.

1. Lag phase: a period of adaptation;

2. Logarithmic phase: rapid growth

3. Stational phase;

4. Decline phase

四. Cultivation of bacteria

(一) Classification of media

(二) The phenomenon of bacterial growth

(三) Significances of Products of medical importance:

1. Pyrogen :

2. Exotoxins :

3. Endotoxins:

4. Antibiotics:

5. Bacteriocin:

6. Vitamin:

Chap 2. Bacterial genetics and variation (3 h)

一. Bacterial variation:

1. Morphological and structure change ;

2. Lose of virulence;

3. Antibiotics-resistant variation.;

4. Colonial variation.

二. Genetic basis of bacteria

(一) Plasmid: F factor ; R factor; Col factor.

(二) Bacteriophage

1. Properties of phage:

2. Relation between host cell and phage:

2.1 Virulent phage; 2.2 T emperate phage (Lysogenic phage)

2.3 Lysogenic state:Prophage; 2.4 Nature of the lysogenic bacteium.

3. Application of phage

(三) transposable element (jumping genes)

三. Mechanism of Bacterial Variation.

(一) Mutation. (self-learning)

(二）Gene transfer and recombination.

1.Transformation: The Naked DNA derive from one cell is taken up by another recipient and DNA recombination can take place.

2. Transduction

Gene transfer mediated by a bacteriophage. i.e. the DNA of one bacterial cell is introduced into another recipient by bacteriophage infection.

(1) Generalized transduction —any of donor genetic information transfer to the chromosome of recipient

(2) Restricted transduction —Bacteriophage can only transfer certain genes from the donor to recipient cells.

3. Lysogenic Conversion: Some bacteria are infected by a temperate phage and their DNA recombinated together and expressed.

4. Conjugation : Many bacteria can transfer genetic information (chromosome, plasmid) through contact of the two cells by way of sex pili

四．Practical Significance of Bacterial Variation

Diagnosis: nontypical strain; Prevention: vaccine; Clinical treatment.

Genetic engineering; Gene thrapy.

Chap. 3 Bacterial Drug-Resistance (3 h)

1．Introduction

Antibiotic resistanc in human and animal; mutiple antibiotic resistance, mar

2. Main mechanisms of antibiotic resistance formation

2.1 Genetic Mechanisms

Plasmid Mediated Drug-Resistance

Drug-resistance could be transmitted by conjugation. transformation and transduction.

Transposon : IS ; Tn ; Mu。

2.2 Biochemical mechanism

Target site modification: PBPs ; DNA gyrase; gyrA, gyrB gene mutation..

modified enzyme:

β–lactamase extended –spectrum β–lactamase

aminoglycoside-modifiled enzymes

active efflux pump

Change of permeability of bacterial cell wall : porin, OmpF ; OmpC。

Biofilm

3. Common drug-resistant bacteria in hospital infection

4. Prevention and treatment principles

Minimal inhibitory concentration , MIC; Minimal bactericidal concentration , MBC

Chap.4 Bacterial infection and pathogenesis (3 h) Normal flora and opportunitists

一. Bacterial infection

(一) infectious sources.

1. Exogenous infection: patients; carrier; animal.

2. Endogenous infection

(二) infectious types

1. Inapparent infection (subclinical infection)

2. Apparent infection: Toxemia; Septicemia; Bacteremia; Pyemia; Endotoxemia.

二. Bacterial Pathogenecity

Virulence: Invasiveness or Toxigenicity

Number of bacterial entry: Portal entry.

Bacterial virulence factors

LD50 (Lethal Dose 50) —the number of microbes that must be administered to kill 50% of the animals.

1. Bacterial related structures: pili, LTA,. capsule,. microcapsule

2. Invasive enzyme Hyaluronidase, Coagulase:

3. Bacterial toxin.: Exotoxin ; Endotoxin ;

Differentiation of exotoxin and endotoxin

三. Pathogenicity of virulent factors:

Superantigen; Pathogenicity island

Chap.5 General properties of viruses (3 h) 一．Size and shape:

二．Structure and composition:

Necleocapsid =Nucleic acid +capsid

Virion = Nucleocapsid (Naked virus)

= Nucleocapsid + Envelope (envelope virus)

三．Multiplication: Replication; Replicative cycle —

1. Adsorption and penetration;

2. Uncoating:;

3. Biosynthesis: SSRNA+ , SSRNA- , Retrovirus,……..

mRNA transcription; Early protein translation; Nucleic acid replication;

(Progency) mRNA transcription; Late protein translation.

4. Assembly, maturation and release.; release by lysis or budding

(二) Growth Curve of virus:

Eclipse phase; Logarithmic phase; cell death phase.

(三) Interference

四. Genetics and Variation

(一) Viral variation types

(二) viral molecular genetics.

(三) practice significance of viral variation.

1. Research in viral pathogenesis;

2. In diagnosis;

3. In treatment ;

4. In prevention;

5. In genetic engineering..

五. Reaction to physical and chemical agents

(一) Physical factors:

1. Temperature:

Resistant to cold —be stored -70℃; Susceptible to heat

2. pH

(二) Chemical factors

六. Classification of viruses

1. Usually according to transmission routes;

2. Subvirus:

①satellites virus (virusoid 拟病毒);

②viroid 类病毒; ③prion 朊粒.

Chap.6 Viral Infection and Pathogenesis (3 h)

一. Infection

1. Transmission and Entrance

(1) Horizontal transmission (between individuals):

(2) V ertical transmission (mother to baby)

2. Spreading within the host

二. Viral infectious forms:

(一) Inapparent viral infection (subclinical infection)

(二) Apparent infection (Dominant infection)

三. Viral Pathogenesis:

(一) Effect on host cell

1. Cytocidal effect;

2. Steady state infection. Cell membrane effect;

3. Cell apoptosis;

4. Integration;

5. Cell transformation;

6. Inclusion body formation (Negribody).

(二) Effect on host

1. Direct damage. Polio.v motor neuron

2. Immunopathology Inflammation

(Type II、III、IV hypersensitivity)

3. Direct effect on immune system

Chap.7 Fungi (2 h)

一. Characteristics:Eucaryotic, including

Unicellular——yeasts.yeast-like organism, cryptococcus neoformans

Multicellular——molds: hyphae spores

Sabouraud’s medium

二. Classification and disease

1. Dermatophytes, causing superficial mycoses (skin, hair, nail).

2. Causing opportunistic mycoses

(1) Candida albicans:

(2) Cryptococcus neoformans

3. Causing allergy;

4. Causing Mycocoxicosis;

5. Causing Cancer-related disease.

三. Detection:

1. direct observed by microscope: hair;

2. Culture:

3. Animal inoculation: cryptococcus neoformans.

Chap.8 Chlamydia (3 h)

C. trachomatis.

1. both DNA+RNA. Binary fission.

2. intracellular multiplication.

Elementaly body——has infectivity.

Initial body——No infectious.

Mycoplasma

1. procaryotic. smallest (0.2~0.3um) free-living microorganisms, no cell wall, highly

pleomorphic, can pass through filtres that retain most bacteria.

2. Colonies minute (<0.2mm), show a “fried-egg appearance”

3. Exist in mouth, respiratory and genito-urinary tracts, common contaminants of tissue-culture.

4. lmportant species:

M. pneumoniae --primary atypical pneumonia; M. hominis ;

genito-urinary infections.; Ureaplasma urealyticum

Spirochete

一. Characteristics:

1. Procaryotic, slender, flexible, helical, actively motile organisms.

2. Not easily to stain, always use: dark-field microscopy for living

specimens silver-impregnation for fixed specimens negative stain

二. Classification:

three genera of pathogenic spirochetes:

1. Leptospira;

2. Treponema:;

3. Borrelia.

Rickettsia

1. Procaryotic

2. Obligate intracellular parasites.

3. Most of them infect both human & animals, transmitted by arthropod vectors.

4. Important species:

5. Share common antigens with certain strains of proteus (OX19, OX2, OX k).

Weil-Felix test is a famous test to help diagnosis

Actinomyces

procaryotic. Taxonomic position between Fungi and bacteria.

Important species——A. Israelii

“sulfur granules”in pus or tissue are diagnostic

Chap. 9 Anti-infection Immunity (3 h) (Human Immunity against Bacterial and Viral Infection)

一. Nonspecific immunity

二. Specific immunity

1. Humoral immunity ;Cellular immunity;

2. Immunity to extracellular bacterium;

3. Immunity to intracellular bacterium;

4. Immunity to exotoxin.

三. Antiviral immunity

1. Non-Specific Immunity (Innate resistance):;

2. Specific Immunity;

3. Synergism of immune factors;

4. Duration of acquired immunity.

Chap.10 Microbiological Diagnosis

Prevention &Treatment of Bacterial and Viral Infection(3 h)

一. Procedure of detection for pathogenic bacteria

1. Sample collection and treatment ; To Smear and Stain;

2. Isolation and Culture;

3. Biological tests;

4. Serological tests. (Identification);

5. Animal tests;

6. Drug－sensitive test;

7. Phage typing ; 8. Molecular technology: fingerprinting ,DNA hybridization; PCR

9. Serological diagnosis : For detection of Antibodies.

二. Microbiologic diagnosis for virus

1. Sample collection and treatment

Rapid diagnosis (Direct identification of virus, viral nucleic acid or viral Ag);

Virus particles —EM or IEM; Inclusion body —microscopy;

Immuno-Label techniques; Other Immunoassay: RIA, ELISA, IF;

Nucleic acid hybridization technique; Isolation and identification of viruses.

2. Culture method selection and cultivation

Animal inoculation ; Egg-embryo inoculation ;

Tissue culture (cell culture): Primary cell ; Cell line ; Blind subculture Recognition of virus growing in cell culture: CPE

Identification: Serological identification; Nucleic acid identification 3: Serologic diagnosis (detect unknown Ab) methods:

4. Quantification of virus either alive or

Electron microscopy inactivated virus

Hemagglutination

Plaque assay (LD50 , 50% Lethal)

50% effect dose (ID50, TCID50) alive virus

三. Prevention (control) and treatment

Enhance the immunity (resistance) of human body

Pyogenic Coccus（3 h）一．Common features and classification .

二．Comparison between staphylococcus and streptococcus . (一)Biological Characterisation :

Morphology and staining ;.Culture;. Ag structure :

(二)Pathogenic substances and diseases caused .

(三)Microbiological diagnosis .

1 . Stained smear .

2 . Isolation and culture . α、β、γstrain

(四)Priniciple of prevention and treatment .

Personal hygiene; Carriers; Hospital cross infection; Patients.

三.Pneumococcus (streptococcus pneumoniae)

Pathogenisis is relate to capsule

Pneumococcal pneumonia

四.Meningococcus

Pathogenisis is related to endotoxin and capsule

Meningitis

五. Gonococcus: Pathogenisis

Enteric bacilli （3 h）

Common properties of Enteric bacilli .

一．Escherichia Coli (E . Coli)

(一) Basic properties :

(二)Pathogenisis :

Apportunitistic bacilli .

Pathogenic E . Coli .

一）Pathogenic factors .

1 . Colonization factor (adhesin)

2 . Enterotoxin (Exotoxin)

Heat Labile erterotoxin(LT) : A TP CAMP

Heat stable enterotoxin(ST) : GTP CGMP

二）diseases .

1 . infection in outside of intestinal tract .

Pyogenic diseases : peritonitis , cholecystitis , pyelitis .

2 . diarrhea

(三). Diagnostic tests:

for pathogen: 1. Specimen: urine, stool , blood. pus.

2. isolation and identification:

Hygienic tests.

二. Shigella and Salmonella

(一) Comparison in biological properties.

(二) Pathogenisis.

1. Pathogenic factors.

2. Infection.

(三)diagnostic laboratory test

Specimens; Procedures:

(四) Prevention and Control

food. feces. fly. fingers.

Vibrio Cholerae （1 h）

(Classical biotype and E1 Tor biotype)

一. Basic Properties.

二. Pathogenisis.

V. Cholerae hibitate only adherence to the intestinal epithelial cellular surface. not enter into cells and blood.

Cholerae enterotoxin: basic structure and pathogenic mechanism.

三. Diagnostic laboratory test.

rapid diagnosis; Culture.

四. Prevention

Anaerobic bacteria （2 h）

(Clostridium)

Cl.Tetani ; Cl.Perfringens ; Cl.Botulinum

一．Common characteristics

Morphology and stain: G+ Bacilli; posses spore.

Culture；Resistant；Exotoxin；

二. Pathogenicity.

*(一) Pathogenic factors:

Cl. Tetani Cl. Perfringens Cl.Botulinum

Tetanospasmin. Tetanolysin; Exotoxin (12)

invasive enzyme;

Exotoxin (8)

(二) Diseases:

三. Prevention and treatment.

四. Diagnostic laboratory tests.

Corynebacterium （1 h）

(diphtheria bacilli)

一. Basic Properties.

*1. Morphology and stain: G+、Club-shaped、Metachromatic granules.

2. Culture:* Loeffler serum medium.

二. Pathogenisis

*1. Pathogenic factors: Exotoxin produced by Lysogenic Corynebacterium. *2. Pathogenic mechanism.diphtheria toxin

3. Diseases.

Endocarditis ; Pseudomembrane ; paralysis of the soft palate.

三. Diagnostic laboratory tests:

Swab from nose, throat.: Abert stain.;

Loeffler serum medium. ; Elek plate test. In vitro

四. Prevention and treatment.

Mycobacterium（2 h）

一. General characteristics

Morphology; Culture.; Resistance

二. Pathogenicity: without exotoxin 、endotoxin and invasive enzymes;

三. Immunity-infecious immunity; old tuberculin (OT),purified protein

derivative (PPD); tuberculin test (principle, procedure, results and explanation).

四, Baterial diagnosis

Specimens-sputum, pus, CSF, stool, urine, etc.

Microscopic examination- Acid fast stain.

Culture- solid culture media method; slide culture media method.

Animal inoculation-guinea pig.

五, Prevention : BCG vaccination.

Influenza virus （2 h）

一. Biological properties

Morphology and structure

Surface antigens: HA, NA

Relationship between the antigenic variation and epidemiology

Antigenic drift: median or small epidemic

Antigenic shift: large scale epidemic

Variation of HA and NA of influenza virus

二. Pathogenicity and immunity

1．Source of infection: patients and carriers.

2. Pathogenesis

3. Laboratory diagnosis

Isolation and identification of viruses.

Serological diagnosis: HI. NT.

4. Prophylaxis and treatment: personal hygiene; vaccines.

Retrovirus （2 h）

一. Basic Properties:

二. Classification: (3 Subfamilies)

H I V

一. Introduction:

二. Epidemiology:

三. Pathogenic mechanism and clinical symptoms:

CD4 recepter;CCR5;CXCR4 ; T4/T8 <1; Cellular Immunity↓

ARC: fever、weight↓、fatique、diarrhea；Kaposi Sarcoma

Opportunistic infection: Fungi. Bacteria..

四. HIV biological properties:

1. Genome: SS RNA.; Structure genes; Regulatory genes

2. Replication.: Reverse transcription

五. Diagnosis:

1. Anti-HIV Positive.;

2. Isolation of HIV from blood.;

3. T4↓. T H/T S <1;

4. HIV RNA : PCR.

六. treatment and Control:

Control: education; blood; blood products;sexal; drug abuser; mother-baby born.

Hepatitis Viruses （3 h）

In general,heptatitis viruses are composed of HA V,HBV,HDV,HCV, HEV and HGV .

一．Hepatitis A virus (HA V)

1. Biological properties

2. Pathogenicity and immunity

Source and transimssion: acute patients; fecal: oral (mainly) Pathogenesis: direct damage and immunopathogenesis.

Immunity: persistant imunity after recovery.

二. Hepatitis B virus (HBV)

1 .Biological properties

Dane particle or HBV: 42nm with double coats; dsDNA.

Small spherical particle: 22nm with HBsAg only.

Tubular or filamentous form: 22nm with 100-700nm in length.

2. Composition of viral antigens

HBsAg: glyco-lipoprotein in viral surface.; Pre-S Ag: pre-S1, pre-S2. HBcAg: protein, viral core Ag.; HBeAg: protein, viral e Ag..

三. Pathogenisis and Immunity.

* 1. Transmission:

Sources: Patients , HBV carriers.

Routes: Parenteral administration; Human Plasma; Blood products, ……；

2. Immuno pathology:

四. Microbiologic diagnosis:

1. Specific Ag & Ab;

2. HBV DNA:

Spot

DNA hybridization techniques

Southern

PCR (Polymerase chain reaction).

3. Dane Particle: IEM ;

4. DNA polymerase:

五. Prevention and treatment.

treatment of patients; Cut off the infectious route ; Immunization.

六. HCV and HEV

Epidemic hemorrhagic fever virus（1 h）

(Hemorrhagic fever with renal syndrom virus)

一. Biological properties:

Sphere, diameter=100nm, SSRNA—; Envelop; Stable: in 4-20℃

Animal reservoir: rodents

二. Transmission and pathogenisis:

Incubation period was 4-16 days.

Bleeding shock, renal failure etc.; Locality and season.

三. Microbiological diagnosis.

1. Viral isolation: from acute serum. Pulmonary. kidney. etc. grows in

cultures of vero-E cells or A549 cells

2. IgM or IgG Ab:

Herpes Virus Family （1 h）

一. Introduction:

二. Biological properties:

1. ds DNA: Surrounded by protein coat (Nucleo-capsid) icosahedral symmetry.

2. Envelope: (Size 150-220 nm): Sphericalvirion

3. DNA replication in cellular nucleus, and budding from nuclear membrane

4. produced intranuclear acidophilic inclusion body.

三. Classification:

四. Microbiolocal diagnosis

1.Isolation of virus:(cell culture);

2.DNA Hybridization;

3..Antibody: IF, ELISA

Hospital infection（nosocomial infection, 2 h）

Classification

一．According to the sources of pathogens.

1. Endogenous nosocomial infection (self-infection)

conolization changed; lower immune function; dysbacteriosis.

2. Exogenous nosocomial infection (cross-infection) patients;

二. According to the infection position；

urinary drainage infections is most common.

surgical infections; skin infection;

三. Common properties of pathogenic microbs

四. prevention and control

1.Asepsis: sterilization and disinfection.

2. Isolation and precaution:

patients; drainage-secretion; blood mainpulation.

3. Antibiotics application in rationality

https://www.360docs.net/doc/547532190.html,anization:

四、教材：

1．医学微生物学，七年制规划教材，贾文祥主编，人民卫生出版社出版，

2001年7月，第一版。

2．医学微生物学，八年制规划教材，贾文祥主编，人民卫生出版社出版，

2005年8月，第一版。

五、主要参考资料

Brooks GF, Butel JS and Morse SA. Jawetz, Melnick & Adelberg’s . Medical Microbiology . 22th ed. Appleton & Lange McGraw-Hill.

六、成绩评定

平时成绩占20%（其中,期中考试占5%），期末考试占80%。