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