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SECTION Ⅰ FUNDAMENTALS OF MICROBIOLOGY&Stephen A. Morse, PhD, and Timothy A. Meitzner, PhD 1

1. The Science of Microbiology 1

Introduction 1

Biologic Principles Illustrated by Microbiology 1

Viruses 2

Prions 2

Prokaryotes 3

Protists 6

Chapter Summary 8

Review Questions 8

2. Cell Structure 11

Optical Methods 11

Eukaryotic Cell Structure 13

Prokaryotic Cell Structure 15

Staining 39

Morphologic Changes During Growth 40

Chapter Summary 40

Review Questions 41

3. Classification of Bacteria 43

Taxonomy—The Vocabulary of Medical Microbiology 43

Criteria for Classification of Bacteria 44

Classification Systems 45

Description of the Major Categories and Groups of Bacteria 48

Subtyping and Its Application 50

Nucleic Acid-Based Taxonomy 51

Nonculture Methods for the Identification of Pathogenic Microorganisms 53

Objectives 53

Review Questions 53

4. The Growth, Survival, and Death of Microorganisms 55

Survival of Microorganisms in the Natural Environment 55

The Meaning of Growth 55

Exponential Growth 55

The Growth Curve 57

Maintenance of Cells in the Exponential Phase 58

Definition and Measurement of Death 58

Antimicrobial Agents 60

Objectives 65

Review Questions 65

5. Cultivation of Microorganisms 67

Requirements for Growth 67

Sources of Metabolic Energy 67

Nutrition 68

Environmental Factors Affecting Growth 69

Cultivation Methods 72

Chapter Summary 75

Review Questions 76

6. Microbial Metabolism 77

Role of Metabolism in Biosynthesis and Growth 77

Focal Metabolites and Their Interconversion 77

Assimilatory Pathways 80

Biosynthetic Pathways 88

Patterns of Microbial Energy-Yielding Metabolism 91

Regulation of Metabolic Pathways 96

Chapter Summary 98

Review Questions 99

7. Microbial Genetics 101

Organization of Genes 101

Replication 106

Transfer of DNA 107

Mutation and Gene Rearrangement 111

Gene Expression 111

Genetic Engineering 115

Characterization of Cloned DNA 118

Site-Directed Mutagenesis 119

Analysis With Cloned DNA: Hybridization Probes 119

Manipulation of Cloned DNA 120

Objectives 121

Objectives 121

SECTION Ⅱ IMMUNOLOGY&Barbara Detrick, PhD 123

8. Immunology 123

Overview 123

Innate Immunity 123

Adaptive Immunity 127

Complement 138

Cytokines 140

Hypersensitivity 141

Deficiencies of the Immune Response 142

Clinical Immunology Laboratory （Diagnostic Testing） 143

Chapter Summary 145

Review Questions 147

SECTIONⅢ BACTERIOLOGY&Karen C. Carroll, MD 149

9. Pathogenesis of Bacterial Infection 149

Identifying Bacteria That Cause Disease 150

Transmission of Infection 151

The Infectious Process 152

Genomics and Bacterial Pathogenicity 152

Regulation of Bacterial Virulence Factors 153

Bacterial Virulence Factors 154

Chapter Summary 161

Review Questions 162

10. Normal Human Microbiota 165

Human Microbiome Project 165

Role of the Resident Microbiota 165

Normal Microbiota of the Skin 167

Normal Microbiota of the Mouth and Upper Respiratory Tract 167

Normal Microbiota of the Urethra 172

Normal Microbiota of the Vagina 172

Normal Microbiota of the Conjunctiva 172

Chapter Summary 172

Review Questions 173

11. Spore-Forming Gram-Positive Bacilli: Bacillus and Clostridium Species 175

Bacillus Species 175

Bacillus anthracis 175

Bacillus cereus 178

Clostridium Species 178

Clostridium botulinum 179

Clostridium tetani 180

Clostridia That Produce Invasive Infections 181

Clostridium difficile and Diarrheal Disease 183

Review Questions 183

12. Aerobic Non-Spore-Forming Gram-Positive Bacilli: Corynebacterium, Listeria,Erysipelothrix, Actinomycetes, and Related Pathogens 187

Corynebacterium diphtheriae 188

Other Coryneform Bacteria 191

Listeria monocytogenes 192

Erysipelothrix rhusiopathiae 193

Actinomycetes 194

Nocardiosis 194

Actinomycetoma 195

Review Questions 195

13. The Staphylococci 199

Chapter Summary 205

Review Questions 206

14. The Streptococci, Enterococci, and Related Genera 209

Classification of Streptococci 209

Streptococci of Particular Medical Interest 211

Streptococcus pyogenes 211

Streptococcus agalactiae 216

Groups C and G 217

Group D Streptococci 217

Streptococcus anginosus Group 217

Group N Streptococci 217

Groups E, F, G, H, and K-U Streptococci 217

Viridans Streptococci 218

Nutritionally Variant Streptococci 218

Peptostreptococcus and Related Genera 218

Streptococcus pneumoniae 218

Enterococci 222

Other Catalase-Negative Gram-Positive Cocci 224

Review Questions 225

15. Enteric Gram-Negative Rods（Enterobacteriaceae） 229

Classification 229

Diseases Caused by Enterobacteriaceae Other Than Salmonella and Shigella 233

The Shigellae 236

The Salmonella-Arizona Group 238

Chapter Summary 241

Review Questions 241

16. Pseudomonads, Acinetobacters, and Uncommon Gram-Negative Bacteria 245

The Pseudomonad Group 245

Pseudomonas aeruginosa 245

Burkholderia pseudomallei 248

Burkholderia mallei 248

Burkholderia cepacia Complex and Burkholderia Gladioli 248

Stenotrophomonas maltophilia 249

Acinetobacter 249

Other Pseudomonads 249

Uncommon Gram-Negative Bacteria 250

Aggregatibacter 250

Achromobacter and Alcaligenes 250

Ochrobactrum 250

Capnocytophaga 250

Cardiobacterium 250

Chromobacteria 250

Eikenella corrodens 251

Chryseobacterium 251

Kingella 251

Moraxella 251

Chapter Summary 251

Review Questions 251

17. Vibrios, Campylobacters, Helicobacter,and Associated Bacteria 255

The Vibrios 255

Vibrio Cholerae 255

Vibrio Parahaemolyticus and Other Vibrios 258

Aeromonas 259

Plesiomonas 259

Campylobacter 259

Campylobacter Jejuni and Campylobacter Coli 259

Campylobacter fetus 261

Other Campylobacters 261

Helicobacter Pylori 261

Review Questions 263

18. Haemophilus, Bordetella, Brucella,and Francisella 265

The Haemophilus Species 265

Haemophilus influenzae 265

Haemophilus aegyptius 267

Aggregatibacter aphrophilus 268

Haemophilus ducreyi 268

Other Haemophilus Species 268

The Bordetellae 268

Bordetella pertussis 268

Bordetella parapertussis 270

Bordetella bronchiseptica 270

The Brucellae 271

Francisella Tularensis and Tularemia 273

Review Questions 275

19. Yersinia and Pasteurella 279

Yersinia pestis and Plague 279

Yersinia enterocolitica and Yersinia pseudotuberculosis 281

Pasteurella 282

Review Questions 282

20. The Neisseriae 285

Neisseria gonorrhoeae 285

Neisseria meningitidis 291

Other Neisseriae 292

Chapter Summary 293

Review Questions 293

21. Infections Caused by Anaerobic Bacteria 295

Physiology and Growth Conditions for Anaerobes 295

Anaerobic Bacteria Found in Human Infections 296

Bacteria That Cause Vaginosis 297

Gardnerella vaginalis 297

Mobiluncus Species 297

Pathogenesis of Anaerobic Infections 300

Immunity in Anaerobic Infections 300

The Polymicrobial Nature of Anaerobic Infections 300

Diagnosis of Anaerobic Infections 301

Treatment of Anaerobic Infections 301

Chapter Summary 301

Review Questions 302

22. Legionellae, Bartonella, and Unusual Bacterial Pathogens 305

Legionella pneumophila and Other Legionellae 305

Bartonella 308

Streptobacillus moniliformis 310

Whipple Disease 310

Review Questions 310

23. Mycobacteria 313

Mycobacterium tuberculosis 313

Other Mycobacteria 321

Mycobacterium leprae 323

Review Questions 324

24. Spirochetes and Other Spiral Microorganisms 327

Treponema 327

Treponema pallidum and Syphilis 327

Diseases Related To Syphilis 331

Borrelia 331

Borrelia Species and Relapsing Fever 331

Borrelia burgdorferi and Lyme Disease 333

Leptospira and Leptospirosis 335

Other Spirochetal Diseases 337

Spirillum minor （Spirillum morsus muris） 337

Spirochetes of the Normal Mouth and Mucous Membranes 337

Review Questions 338

25. Mycoplasmas and Cell Wall-Defective Bacteria 341

Mycoplasmas 341

Mycoplasma pneumoniae and Atypical Pneumonias 343

Mycoplasma hominis 344

Ureaplasma urealyticum 345

Mycoplasma genitalium 345

Cell Wall-Defective Bacteria 345

Chapter Summary 345

Review Questions 345

26. Rickettsia and Related Genera 349

General 349

Rickettsia and Orientia 349

Ehrlichia and Anaplasma 353

Coxiella Burnetii 354

Review Questions 356

27. Chlamydia Spp. 359

Chlamydia Trachomatis Ocular, Genital, and Respiratory Infections 362

Trachoma 362

Chlamydia trachomatis Genital Infections and Inclusion Conjunctivitis 363

Chlamydia Trachomatis And Neonatal Pneumonia 364

Lymphogranuloma Venereum 364

Chlamydia pneumoniae and Respiratory Infections 365

Chlamydia psittaci and Psittacosis 366

Chapter Summary 368

Review Questions 368

28. Antimicrobial Chemotherapy 371

Mechanisms Of Action Of Antimicrobial Drugs 371

Selective Toxicity 371

Inhibition of Cell Wall Synthesis 371

Inhibition of Cell Membrane Function 373

Inhibition of Protein Synthesis 373

Inhibition of Nucleic Acid Synthesis 375

Resistance To Antimicrobial Drugs 375

Origin of Drug Resistance 376

Cross-Resistance 376

Limitation of Drug Resistance 376

Clinical Implications of Drug Resistance 377

Factors Affecting Antimicrobial Activity 378

Antimicrobial Activity In Vitro 378

Measurement of Antimicrobial Activity 379

Drug-Pathogen Relationships 379

Antimicrobial Activity In Vivo 379

Host-Pathogen Relationships 380

Clinical Use Of Antibiotics 381

Selection of Antibiotics 381

Dangers of Indiscriminate Use 381

Antimicrobial Drugs Used in Combination 382

Antimicrobial Chemoprophylaxis 383

Antimicrobial Drugs For Systemic Administration 384

Penicillins 384

Cephalosporins 390

Other β-Lactam Drugs 393

Tetracyclines 394

Glycylcyclines 394

Chloramphenicol 395

Erythromycins 395

Clindamycin and Lincomycin 396

Glycopeptides and Lipopeptides 396

Streptogramins 397

Oxazolidinones 397

Bacitracin 397

Polymyxins 397

Aminoglycosides 398

Quinolones 399

Sulfonamides and Trimethoprim 401

Other Drugs With Specialized Uses 401

Drugs Used Primarily To Treat Mycobacterial Infections 402

Review Questions 403

SECTION Ⅳ VIROLOGY&Jane Butel, PhD 407

29. General Properties of Viruses 407

Terms and Definitions in Virology 407

Evolutionary Origin of Viruses 408

Classification of Viruses 408

Principles of Virus Structure 414

Chemical Composition of Viruses 415

Cultivation and Assay of Viruses 416

Purification and Identification of Viruses 418

Laboratory Safety 419

Reaction To Physical and Chemical Agents 419

Replication of Viruses: An Overview 420

Genetics of Animal Viruses 425

Natural History （Ecology） and Modes of Transmission of Viruses 427

Chapter Summary 428

Review Questions 429

30. Pathogenesis and Control of Viral Diseases 431

Principles of Viral Diseases 431

Pathogenesis of Viral Diseases 431

Prevention and Treatment of Viral Infections 441

Chapter Summary 449

Review Questions 449

31.Parvoviruses 451

Properties of Parvoviruses 451

Parvovirus Infections in Humans 452

Chapter Summary 455

Review Questions 455

32. Adenoviruses 457

Properties of Adenoviruses 457

Adenovirus Infections in Humans 461

Chapter Summary 464

Review Questions 464

33.Herpesviruses 467

Properties of Herpesviruses 467

Herpesvirus Infections in Humans 471

Herpes Simplex Viruses 471

Varicella-Zoster Virus 476

Cytomegalovirus 480

Epstein-Barr Virus 484

Human Herpesvirus 6 487

Human Herpesvirus 7 487

Human Herpesvirus 8 488

B Virus 488

Chapter Summary 489

Review Questions 489

34. Poxviruses 493

Properties of Poxviruses 493

Poxvirus Infections in Humans: Vaccinia and Variola 496

Monkeypox Infections 501

Cowpox Infections 501

Buffalopox Infections 501

Orf Virus Infections 501

Molluscum Contagiosum 501

Tanapox and Yaba Monkey Tumor Poxvirus Infections 503

Chapter Summary 504

Review Questions 504

35. Hepatitis Viruses 507

Properties of Hepatitis Viruses 507

Hepatitis Virus Infections in Humans 512

Chapter Summary 524

Review Questions 524

36. Picornaviruses （Enterovirus and Rhinovirus Groups） 527

Properties of Picornaviruses 527

Enterovirus Group 531

Polioviruses 531

Coxsackieviruses 533

Other Enteroviruses 536

Enteroviruses in the Environment 537

Rhinoviruses 538

Parechovirus Group 539

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

Chapter Summary 540

Review Questions 540

37. Reoviruses, Rotaviruses, and Caliciviruses 543

Reoviruses and Rotaviruses 543

Rotaviruses 544

Reoviruses 548

Caliciviruses 548

Orbiviruses and Coltiviruses 548

Astroviruses 551

Chapter Summary 551

Review Questions 551

38. Arthropod-Borne and Rodent-Borne Viral Diseases 553

Human Arbovirus Infections 553

Togavirus and Flavivirus Encephalitis 555

Yellow Fever 562

Dengue 564

Bunyavirus Encephalitis 566

Sandfly Fever 566

Rift Valley Fever 566

Colorado Tick Fever 567

Rodent-Borne Hemorrhagic Fevers 567

Bunyavirus Diseases 567

Arenavirus Diseases 569

Filovirus Diseases 571

Chapter Summary 573

Review Questions 573

39. Orthomyxoviruses （Influenza Viruses） 577

Properties of Orthomyxoviruses 577

Influenza Virus Infections in Humans 583

Chapter Summary 588

Review Questions 589

40. Paramyxoviruses and Rubella Virus 591

Properties of Paramyxoviruses 591

Parainfluenza Virus Infections 594

Respiratory Syncytial Virus Infections 598

Human Metapneumovirus Infections 600

Mumps Virus Infections 601

Measles （Rubeola） Virus Infections 603

Hendra Virus and Nipah Virus Infections 606

Rubella （German Measles） Virus Infections 607

Postnatal Rubella 607

Congenital Rubella Syndrome 609

Chapter Summary 609

Review Questions 610

41. Coronaviruses 613

Properties of Coronaviruses 613

Coronavirus Infections in Humans 615

Chapter Summary 617

Review Questions 617

42. Rabies, Slow Virus Infections, and Prion Diseases 619

Rabies 619

Borna Disease 626

Slow Virus Infections and Prion Diseases 626

Chapter Summary 629

Review Questions 629

43. Human Cancer Viruses 633

General Features of Viral Carcinogenesis 633

Retroviruses 635

Cellular Oncogenes 641

Tumor Suppressor Genes 642

DNA Tumor Viruses 642

Polyomaviruses 642

Papillomaviruses 644

Adenoviruses 647

Herpesviruses 648

Poxviruses 648

Hepatitis B Virus and Hepatitis C Virus 648

How to Prove That a Virus Causes Human Cancer 649

Chapter Summary 649

Review Questions 649

44. AIDS and Lentiviruses 653

Properties of Lentiviruses 653

HIV Infections in Humans 657

Chapter Summary 667

Review Questions 667

SECTION Ⅴ MYCOLOGY&Thomas G.Mitchell,PhD 671

45. Medical Mycology 671

General Properties and Classification of Fungi 672

Growth and Isolation of Fungi 676

Superficial Mycoses 676

Cutaneous Mycoses 677

Key Concepts: Superficial and Cutaneous Mycoses 681

Subcutaneous Mycoses 681

Sporotrichosis 681

Chromoblastomycosis 682

Phaeohyphomycosis 684

Mycetoma 684

Key Concepts: Subcutaneous Mycoses 685

Endemic Mycoses 685

Coccidioidomycosis 686

Histoplasmosis 689

Blastomycosis 692

Paracoccidioidomycosis 693

Key Concepts: Endemic Mycoses 694

Opportunistic Mycoses 694

Candidiasis 694

Cryptococcosis 697

Aspergillosis 699

Mucormycosis 701

Pneumocystis Pneumonia 702

Penicilliosis 702

Other Opportunistic Mycoses 702

Key Concepts: Opportunistic Mycoses 703

Antifungal Prophylaxis 703

Hypersensitivity to Fungi 703

Mycotoxins 704

Antifungal Chemotherapy 704

Topical Antifungal Agents 709

Key Concepts: Antifungal Chemotherapy 710

Review Questions 710

SECTION Ⅵ PARASITOLOGY&Judy A.S 715

46. Medical Parasitology 715

Classification of Parasites 715

Intestinal Protozoan Infections 719

Giardia lamblia （Intestinal Flagellate） 719

Key Concepts: Parasitic Protozoa 719

Entamoeba histolytica （Intestinal and Tissue Ameba） 720

Other Intestinal Amebae 722

Cryptosporidium （Intestinal Sporozoa） 722

Cyclospora （Intestinal Sporozoa） 723

Sexually Transmitted Protozoan Infection 723

Trichomonas vaginalis （Genitourinary Flagellate） 723

Blood and Tissue Protozoan Infections 723

Blood Flagellates 723

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 Section 727

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

Microsporidia 733

Intestinal Helminthic Infections 733

Key Concepts: Parasitic Helminths 733

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 Infections 743

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）—TissueTrematodes 745

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

Tissue Cestode Infections （Caused by the LarvalStages） 746

Taenia solium—Cysticercosis/Neurocysticercosis 746

Echinococcus granulosus （Hydatid Cyst） 746

Review Questions 748

SECTION Ⅶ DIAGNOSTIC MEDICAL MICROBIOLOGY AND CLINICAL CORRELATION&Karen C.Carroll,MD 753

47. Principles of Diagnostic Medical Microbiology 753

Communication Between Physician and Laboratory 753

Diagnosis of Bacterial and Fungal Infections 754

The Importance of Normal Bacterial and Fungal Microbiota 765

Laboratory Aids in the Selection of Antimicrobial Therapy 766

Diagnosis of Infection by Anatomic Site 767

Anaerobic Infections 773

Diagnosis of Chlamydial Infections 773

Diagnosis of Viral Infections 775

Review Questions 783

48. Cases and Clinical Correlations 785

Central Nervous System 785

Respiratory 789

Heart 793

Abdomen 795

Urinary Tract 800

Bone and Soft Tissue 802

Sexually Transmitted Diseases 803

Mycobacterium Tuberculosis Infections 806

HIV-1 and Aids 809

Infections in Transplant Patients 813

Biologic Warfare and Bioterrorism 817