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SECTION Ⅰ FUNDAMENTALS OF MICROBIOLOGY&Stephen A. Morse, PhD, and Timothy A. Meitzner, PhD1

1. The Science of Microbiology1

Introduction1

Biologic Principles Illustrated by Microbiology1

Viruses2

Prions2

Prokaryotes3

Protists6

Chapter Summary8

Review Questions8

2. Cell Structure11

Optical Methods11

Eukaryotic Cell Structure13

Prokaryotic Cell Structure15

Staining39

Morphologic Changes During Growth40

Chapter Summary40

Review Questions41

3. Classification of Bacteria43

Taxonomy—The Vocabulary of Medical Microbiology43

Criteria for Classification of Bacteria44

Classification Systems45

Description of the Major Categories and Groups of Bacteria48

Subtyping and Its Application50

Nucleic Acid-Based Taxonomy51

Nonculture Methods for the Identification of Pathogenic Microorganisms53

Objectives53

Review Questions53

4. The Growth, Survival, and Death of Microorganisms55

Survival of Microorganisms in the Natural Environment55

The Meaning of Growth55

Exponential Growth55

The Growth Curve57

Maintenance of Cells in the Exponential Phase58

Definition and Measurement of Death58

Antimicrobial Agents60

Objectives65

Review Questions65

5. Cultivation of Microorganisms67

Requirements for Growth67

Sources of Metabolic Energy67

Nutrition68

Environmental Factors Affecting Growth69

Cultivation Methods72

Chapter Summary75

Review Questions76

6. Microbial Metabolism77

Role of Metabolism in Biosynthesis and Growth77

Focal Metabolites and Their Interconversion77

Assimilatory Pathways80

Biosynthetic Pathways88

Patterns of Microbial Energy-Yielding Metabolism91

Regulation of Metabolic Pathways96

Chapter Summary98

Review Questions99

7. Microbial Genetics101

Organization of Genes101

Replication106

Transfer of DNA107

Mutation and Gene Rearrangement111

Gene Expression111

Genetic Engineering115

Characterization of Cloned DNA118

Site-Directed Mutagenesis119

Analysis With Cloned DNA: Hybridization Probes119

Manipulation of Cloned DNA120

Objectives121

Objectives121

SECTION Ⅱ IMMUNOLOGY&Barbara Detrick, PhD123

8. Immunology123

Overview123

Innate Immunity123

Adaptive Immunity127

Complement138

Cytokines140

Hypersensitivity141

Deficiencies of the Immune Response142

Clinical Immunology Laboratory （Diagnostic Testing）143

Chapter Summary145

Review Questions147

SECTIONⅢ BACTERIOLOGY&Karen C. Carroll, MD149

9. Pathogenesis of Bacterial Infection149

Identifying Bacteria That Cause Disease150

Transmission of Infection151

The Infectious Process152

Genomics and Bacterial Pathogenicity152

Regulation of Bacterial Virulence Factors153

Bacterial Virulence Factors154

Chapter Summary161

Review Questions162

10. Normal Human Microbiota165

Human Microbiome Project165

Role of the Resident Microbiota165

Normal Microbiota of the Skin167

Normal Microbiota of the Mouth and Upper Respiratory Tract167

Normal Microbiota of the Urethra172

Normal Microbiota of the Vagina172

Normal Microbiota of the Conjunctiva172

Chapter Summary172

Review Questions173

11. Spore-Forming Gram-Positive Bacilli: Bacillus and Clostridium Species175

Bacillus Species175

Bacillus anthracis175

Bacillus cereus178

Clostridium Species178

Clostridium botulinum179

Clostridium tetani180

Clostridia That Produce Invasive Infections181

Clostridium difficile and Diarrheal Disease183

Review Questions183

12. Aerobic Non-Spore-Forming Gram-Positive Bacilli: Corynebacterium, Listeria,Erysipelothrix, Actinomycetes, and Related Pathogens187

Corynebacterium diphtheriae188

Other Coryneform Bacteria191

Listeria monocytogenes192

Erysipelothrix rhusiopathiae193

Actinomycetes194

Nocardiosis194

Actinomycetoma195

Review Questions195

13. The Staphylococci199

Chapter Summary205

Review Questions206

14. The Streptococci, Enterococci, and Related Genera209

Classification of Streptococci209

Streptococci of Particular Medical Interest211

Streptococcus pyogenes211

Streptococcus agalactiae216

Groups C and G217

Group D Streptococci217

Streptococcus anginosus Group217

Group N Streptococci217

Groups E, F, G, H, and K-U Streptococci217

Viridans Streptococci218

Nutritionally Variant Streptococci218

Peptostreptococcus and Related Genera218

Streptococcus pneumoniae218

Enterococci222

Other Catalase-Negative Gram-Positive Cocci224

Review Questions225

15. Enteric Gram-Negative Rods（Enterobacteriaceae）229

Classification229

Diseases Caused by Enterobacteriaceae Other Than Salmonella and Shigella233

The Shigellae236

The Salmonella-Arizona Group238

Chapter Summary241

Review Questions241

16. Pseudomonads, Acinetobacters, and Uncommon Gram-Negative Bacteria245

The Pseudomonad Group245

Pseudomonas aeruginosa245

Burkholderia pseudomallei248

Burkholderia mallei248

Burkholderia cepacia Complex and Burkholderia Gladioli248

Stenotrophomonas maltophilia249

Acinetobacter249

Other Pseudomonads249

Uncommon Gram-Negative Bacteria250

Aggregatibacter250

Achromobacter and Alcaligenes250

Ochrobactrum250

Capnocytophaga250

Cardiobacterium250

Chromobacteria250

Eikenella corrodens251

Chryseobacterium251

Kingella251

Moraxella251

Chapter Summary251

Review Questions251

17. Vibrios, Campylobacters, Helicobacter,and Associated Bacteria255

The Vibrios255

Vibrio Cholerae255

Vibrio Parahaemolyticus and Other Vibrios258

Aeromonas259

Plesiomonas259

Campylobacter259

Campylobacter Jejuni and Campylobacter Coli259

Campylobacter fetus261

Other Campylobacters261

Helicobacter Pylori261

Review Questions263

18. Haemophilus, Bordetella, Brucella,and Francisella265

The Haemophilus Species265

Haemophilus influenzae265

Haemophilus aegyptius267

Aggregatibacter aphrophilus268

Haemophilus ducreyi268

Other Haemophilus Species268

The Bordetellae268

Bordetella pertussis268

Bordetella parapertussis270

Bordetella bronchiseptica270

The Brucellae271

Francisella Tularensis and Tularemia273

Review Questions275

19. Yersinia and Pasteurella279

Yersinia pestis and Plague279

Yersinia enterocolitica and Yersinia pseudotuberculosis281

Pasteurella282

Review Questions282

20. The Neisseriae285

Neisseria gonorrhoeae285

Neisseria meningitidis291

Other Neisseriae292

Chapter Summary293

Review Questions293

21. Infections Caused by Anaerobic Bacteria295

Physiology and Growth Conditions for Anaerobes295

Anaerobic Bacteria Found in Human Infections296

Bacteria That Cause Vaginosis297

Gardnerella vaginalis297

Mobiluncus Species297

Pathogenesis of Anaerobic Infections300

Immunity in Anaerobic Infections300

The Polymicrobial Nature of Anaerobic Infections300

Diagnosis of Anaerobic Infections301

Treatment of Anaerobic Infections301

Chapter Summary301

Review Questions302

22. Legionellae, Bartonella, and Unusual Bacterial Pathogens305

Legionella pneumophila and Other Legionellae305

Bartonella308

Streptobacillus moniliformis310

Whipple Disease310

Review Questions310

23. Mycobacteria313

Mycobacterium tuberculosis313

Other Mycobacteria321

Mycobacterium leprae323

Review Questions324

24. Spirochetes and Other Spiral Microorganisms327

Treponema327

Treponema pallidum and Syphilis327

Diseases Related To Syphilis331

Borrelia331

Borrelia Species and Relapsing Fever331

Borrelia burgdorferi and Lyme Disease333

Leptospira and Leptospirosis335

Other Spirochetal Diseases337

Spirillum minor （Spirillum morsus muris）337

Spirochetes of the Normal Mouth and Mucous Membranes337

Review Questions338

25. Mycoplasmas and Cell Wall-Defective Bacteria341

Mycoplasmas341

Mycoplasma pneumoniae and Atypical Pneumonias343

Mycoplasma hominis344

Ureaplasma urealyticum345

Mycoplasma genitalium345

Cell Wall-Defective Bacteria345

Chapter Summary345

Review Questions345

26. Rickettsia and Related Genera349

General349

Rickettsia and Orientia349

Ehrlichia and Anaplasma353

Coxiella Burnetii354

Review Questions356

27. Chlamydia Spp.359

Chlamydia Trachomatis Ocular, Genital, and Respiratory Infections362

Trachoma362

Chlamydia trachomatis Genital Infections and Inclusion Conjunctivitis363

Chlamydia Trachomatis And Neonatal Pneumonia364

Lymphogranuloma Venereum364

Chlamydia pneumoniae and Respiratory Infections365

Chlamydia psittaci and Psittacosis366

Chapter Summary368

Review Questions368

28. Antimicrobial Chemotherapy371

Mechanisms Of Action Of Antimicrobial Drugs371

Selective Toxicity371

Inhibition of Cell Wall Synthesis371

Inhibition of Cell Membrane Function373

Inhibition of Protein Synthesis373

Inhibition of Nucleic Acid Synthesis375

Resistance To Antimicrobial Drugs375

Origin of Drug Resistance376

Cross-Resistance376

Limitation of Drug Resistance376

Clinical Implications of Drug Resistance377

Factors Affecting Antimicrobial Activity378

Antimicrobial Activity In Vitro378

Measurement of Antimicrobial Activity379

Drug-Pathogen Relationships379

Antimicrobial Activity In Vivo379

Host-Pathogen Relationships380

Clinical Use Of Antibiotics381

Selection of Antibiotics381

Dangers of Indiscriminate Use381

Antimicrobial Drugs Used in Combination382

Antimicrobial Chemoprophylaxis383

Antimicrobial Drugs For Systemic Administration384

Penicillins384

Cephalosporins390

Other β-Lactam Drugs393

Tetracyclines394

Glycylcyclines394

Chloramphenicol395

Erythromycins395

Clindamycin and Lincomycin396

Glycopeptides and Lipopeptides396

Streptogramins397

Oxazolidinones397

Bacitracin397

Polymyxins397

Aminoglycosides398

Quinolones399

Sulfonamides and Trimethoprim401

Other Drugs With Specialized Uses401

Drugs Used Primarily To Treat Mycobacterial Infections402

Review Questions403

SECTION Ⅳ VIROLOGY&Jane Butel, PhD407

29. General Properties of Viruses407

Terms and Definitions in Virology407

Evolutionary Origin of Viruses408

Classification of Viruses408

Principles of Virus Structure414

Chemical Composition of Viruses415

Cultivation and Assay of Viruses416

Purification and Identification of Viruses418

Laboratory Safety419

Reaction To Physical and Chemical Agents419

Replication of Viruses: An Overview420

Genetics of Animal Viruses425

Natural History （Ecology） and Modes of Transmission of Viruses427

Chapter Summary428

Review Questions429

30. Pathogenesis and Control of Viral Diseases431

Principles of Viral Diseases431

Pathogenesis of Viral Diseases431

Prevention and Treatment of Viral Infections441

Chapter Summary449

Review Questions449

31.Parvoviruses451

Properties of Parvoviruses451

Parvovirus Infections in Humans452

Chapter Summary455

Review Questions455

32. Adenoviruses457

Properties of Adenoviruses457

Adenovirus Infections in Humans461

Chapter Summary464

Review Questions464

33.Herpesviruses467

Properties of Herpesviruses467

Herpesvirus Infections in Humans471

Herpes Simplex Viruses471

Varicella-Zoster Virus476

Cytomegalovirus480

Epstein-Barr Virus484

Human Herpesvirus 6487

Human Herpesvirus 7487

Human Herpesvirus 8488

B Virus488

Chapter Summary489

Review Questions489

34. Poxviruses493

Properties of Poxviruses493

Poxvirus Infections in Humans: Vaccinia and Variola496

Monkeypox Infections501

Cowpox Infections501

Buffalopox Infections501

Orf Virus Infections501

Molluscum Contagiosum501

Tanapox and Yaba Monkey Tumor Poxvirus Infections503

Chapter Summary504

Review Questions504

35. Hepatitis Viruses507

Properties of Hepatitis Viruses507

Hepatitis Virus Infections in Humans512

Chapter Summary524

Review Questions524

36. Picornaviruses （Enterovirus and Rhinovirus Groups）527

Properties of Picornaviruses527

Enterovirus Group531

Polioviruses531

Coxsackieviruses533

Other Enteroviruses536

Enteroviruses in the Environment537

Rhinoviruses538

Parechovirus Group539

Foot-And-Mouth Disease （Aphthovirus Of Cattle）539

Chapter Summary540

Review Questions540

37. Reoviruses, Rotaviruses, and Caliciviruses543

Reoviruses and Rotaviruses543

Rotaviruses544

Reoviruses548

Caliciviruses548

Orbiviruses and Coltiviruses548

Astroviruses551

Chapter Summary551

Review Questions551

38. Arthropod-Borne and Rodent-Borne Viral Diseases553

Human Arbovirus Infections553

Togavirus and Flavivirus Encephalitis555

Yellow Fever562

Dengue564

Bunyavirus Encephalitis566

Sandfly Fever566

Rift Valley Fever566

Colorado Tick Fever567

Rodent-Borne Hemorrhagic Fevers567

Bunyavirus Diseases567

Arenavirus Diseases569

Filovirus Diseases571

Chapter Summary573

Review Questions573

39. Orthomyxoviruses （Influenza Viruses）577

Properties of Orthomyxoviruses577

Influenza Virus Infections in Humans583

Chapter Summary588

Review Questions589

40. Paramyxoviruses and Rubella Virus591

Properties of Paramyxoviruses591

Parainfluenza Virus Infections594

Respiratory Syncytial Virus Infections598

Human Metapneumovirus Infections600

Mumps Virus Infections601

Measles （Rubeola） Virus Infections603

Hendra Virus and Nipah Virus Infections606

Rubella （German Measles） Virus Infections607

Postnatal Rubella607

Congenital Rubella Syndrome609

Chapter Summary609

Review Questions610

41. Coronaviruses613

Properties of Coronaviruses613

Coronavirus Infections in Humans615

Chapter Summary617

Review Questions617

42. Rabies, Slow Virus Infections, and Prion Diseases619

Rabies619

Borna Disease626

Slow Virus Infections and Prion Diseases626

Chapter Summary629

Review Questions629

43. Human Cancer Viruses633

General Features of Viral Carcinogenesis633

Retroviruses635

Cellular Oncogenes641

Tumor Suppressor Genes642

DNA Tumor Viruses642

Polyomaviruses642

Papillomaviruses644

Adenoviruses647

Herpesviruses648

Poxviruses648

Hepatitis B Virus and Hepatitis C Virus648

How to Prove That a Virus Causes Human Cancer649

Chapter Summary649

Review Questions649

44. AIDS and Lentiviruses653

Properties of Lentiviruses653

HIV Infections in Humans657

Chapter Summary667

Review Questions667

SECTION Ⅴ MYCOLOGY&Thomas G.Mitchell,PhD671

45. Medical Mycology671

General Properties and Classification of Fungi672

Growth and Isolation of Fungi676

Superficial Mycoses676

Cutaneous Mycoses677

Key Concepts: Superficial and Cutaneous Mycoses681

Subcutaneous Mycoses681

Sporotrichosis681

Chromoblastomycosis682

Phaeohyphomycosis684

Mycetoma684

Key Concepts: Subcutaneous Mycoses685

Endemic Mycoses685

Coccidioidomycosis686

Histoplasmosis689

Blastomycosis692

Paracoccidioidomycosis693

Key Concepts: Endemic Mycoses694

Opportunistic Mycoses694

Candidiasis694

Cryptococcosis697

Aspergillosis699

Mucormycosis701

Pneumocystis Pneumonia702

Penicilliosis702

Other Opportunistic Mycoses702

Key Concepts: Opportunistic Mycoses703

Antifungal Prophylaxis703

Hypersensitivity to Fungi703

Mycotoxins704

Antifungal Chemotherapy704

Topical Antifungal Agents709

Key Concepts: Antifungal Chemotherapy710

Review Questions710

SECTION Ⅵ PARASITOLOGY&Judy A.S715

46. Medical Parasitology715

Classification of Parasites715

Intestinal Protozoan Infections719

Giardia lamblia （Intestinal Flagellate）719

Key Concepts: Parasitic Protozoa719

Entamoeba histolytica （Intestinal and Tissue Ameba）720

Other Intestinal Amebae722

Cryptosporidium （Intestinal Sporozoa）722

Cyclospora （Intestinal Sporozoa）723

Sexually Transmitted Protozoan Infection723

Trichomonas vaginalis （Genitourinary Flagellate）723

Blood and Tissue Protozoan Infections723

Blood Flagellates723

Trypanosoma brucei rhodesiense and T b gambiense （Blood Flagellates）724

Trypanosoma cruzi （Blood Flagellate）725

Leishmania Species （Blood Flagellates）725

Entamoeba histolytica （Tissue Ameba）—See Intestinal Protozoan Infections Section727

Naegleria fowleri, Acanthamoeba castellanii,and Balamuthia mandrillaris （Free-LivingAmebae）727

Plasmodium Species （Blood Sporozoa）727

Babesia microti （Blood Sporozoa）731

Toxoplasma gondii （Tissue Sporozoa）732

Microsporidia733

Intestinal Helminthic Infections733

Key Concepts: Parasitic Helminths733

Enterobius vermicularis （Pinworm—IntestinalNematode）734

Trichuris trichiura （Whipworm—IntestinalNematode）734

Ascaris lumbricoides （Human Roundworm—Intestinal Nematode）738

Ancylostoma duodenale and Necator americanus（Human Hookworms—Intestinal Nematode）739

Strongyloides stercoralis （Human Threadworm—Intestinal and Tissue Nematode）740

Trichinella spiralis （Intestinal And TissueNematode）741

Fasciolopsis buski （Giant Intestinal Fluke—Intestinal Trematode）741

Taenia saginata （Beef Tapeworm—IntestinalCestode） and Taenia Solium （Pork Tapeworm—Intestinal and Tissue Cestode）741

Diphyllobothrium latum （Broad Fish Tapeworm—Intestinal Cestode）742

Hymenolepis nana （Dwarf Tapeworm—IntestinalCestode）742

Dipylidium caninum （Dog Tapeworm—IntestinalCestode）743

Wuchereria bancrofti and BrugiaMalayi （Lymphatic Filariasis—TissueNematodes）743

Blood and Tissue Helminthic Infections743

Onchocerca volvulus （River Blindness—TissueNematode）743

Dracunculus medinensis （Guinea Worm—TissueNematode）744

Larva Migrans （Zoonotic Larval NematodeInfections）745

Clonorchis sinensis （Chinese Liver Fluke）,Fasciola hepatica （Sheep Liver Fluke）, andParagonimus westermani （Lung Fluke）—TissueTrematodes745

Schistosoma mansoni, S japonicum, and Shaematobium （Blood Flukes）746

Tissue Cestode Infections （Caused by the LarvalStages）746

Taenia solium—Cysticercosis/Neurocysticercosis746

Echinococcus granulosus （Hydatid Cyst）746

Review Questions748

SECTION Ⅶ DIAGNOSTIC MEDICAL MICROBIOLOGY AND CLINICAL CORRELATION&Karen C.Carroll,MD753

47. Principles of Diagnostic Medical Microbiology753

Communication Between Physician and Laboratory753

Diagnosis of Bacterial and Fungal Infections754

The Importance of Normal Bacterial and Fungal Microbiota765

Laboratory Aids in the Selection of Antimicrobial Therapy766

Diagnosis of Infection by Anatomic Site767

Anaerobic Infections773

Diagnosis of Chlamydial Infections773

Diagnosis of Viral Infections775

Review Questions783

48. Cases and Clinical Correlations785

Central Nervous System785

Respiratory789

Heart793

Abdomen795

Urinary Tract800

Bone and Soft Tissue802

Sexually Transmitted Diseases803

Mycobacterium Tuberculosis Infections806

HIV-1 and Aids809

Infections in Transplant Patients813

Biologic Warfare and Bioterrorism817