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Contents Preface xi

SECTION

I The Meaning of Growth 53 Exponential Growth 53 The Growth Curve 55 Maintenance of Cells in the Exponential Phase 56 Definition & Measurement of Death Antimicrobial Agents 58 Review Questions 62

FUNDAMENTALS OF

MICROBIOLOGY

1

StephenA. Morse,PhD,* and

TimothyA. Meitzner, PhD 1.

2.

3.

4.

The Science of Microbiology 1 Introduction 1 BiologicPrincipIes Illustrated by Microbiology Viruses 2 Prions 2 Prokaryotes 3 Protists 5 ReviewQuestions 7 Cell Structure 9 Introduction 9 Optical Methods 9 Eukaryotic Cell Structure 11 Prokaryotic Cell Structure 13 Staining 36 Morphologic Changes During Growth ReviewQuestions 38

1

5.

Cultivation of Microorganisms 65 Requirements for Growth 65 Sources of Metabolic Energy 65 Nutrition 66 Environmental Factors Affecting Growth 67 Cultivation Methods 70 Review Questions 73

6.

Microbial Metabolism 75 Role of Metabolism in Biosynthesis & Growth 75 Focal Metabolites & Their Interconversion 75 Assimilatory Pathways 80 Biosynthetic Pathways 85 Patterns of Microbial Energy-Yielding Metabolism 87 Regulation of Metabolic Pathways 94 ReviewQuestions 96

7.

Microbial Genetics

37

Classification of Bacteria 41 Criteria for Classification of Bacteria 42 Classification Systems 43 Description of the Major Cat,egories& Groups of Bacteria 44 Subtyping & Its Application 47 Nucleic Acid-Based Taxonomy 48 Nonculture Methods for the Identification of Pathogenic Microorganisms 50 ReviewQuestions 51 The Growth, Survival, & Death of Microorganisms 53 Survival of Microorganisms in the Natural Environment 53

56

97

Organization of Genes 97 Replication 102 Transfer ofDNA 103 Mutation & Gene Rearrangement Gene Expression 108 Genetic Engineering 111 Characterization of Cloned DNA Site- Directed Mutagenesis

116

107

113

Analysis with Cloned DNA: Hybridization Probes 117 Manipulation of Cloned DNA 117 ReviewQuestions 118 SECTION

11

IMMUNOLOGY

121

Roderick Nairn, PhD

8. Immunology 121 Immunity & the Immune Response 121 Mechanisms of Innate Immunity 124 Mechanisms of SpecificHost Defense 126 Antigen Recognition Molecules 127 Antibodies 128 Cell Surface Receptors for Antigen 131 Antibody-Mediated (Humoral) Immunity 135 The Complement System 136 Cell-Mediated Immunity 138 Cytokines 140 Hypersensitivity 140 Inadequate Immune Responses to Infectious Agents 142 Immunologic Diagnostic Tests 142 ReviewQuestions 143 SECTION

111

BACTERIOLOGY 145 Geo.F.Brooks,MD, and Karen C. Carroll, MD

9. Pathogenesisof BacterialInfection 145 Identifying Bacteria That Cause Disease 146 Transmission ofInfection 147 The Infectious Process 147 Genomics & Bacterial Pathogenicity 148 Regulation of Bacterial Virulence Factors 148 Bacterial Virulence Factors 149 ReviewQuestions 157 10. Normal Human Microbiota 159 Role of the Resident Microbiota 159 Normal Microbiota of the Skin 160 Normal Microbiota of the Mouth & Upper Respiratory Tract 161 Normal Microbiota of the Intestinal Tract 162 Normal Microbiota of the Urethra 163 Normal Microbiota of the Vagina 163 Normal Microbiota of the Conjunctiva 163 ReviewQuestions 163

11.

Spore-Forming

Gram-Positive

Bacillus & Clostridium Species Bacillus Species 165

Bacilli: 165

Bacillus anthracis 165 Bacillus cereus 167 Clostridium Species 168 Clostridium botulinum 169 Clostridium tetani 170 Clostridia That Produce Invasive Infections

Clostridium difficile & Diarrheal Disease ReviewQuestions 173

171

172

12. Aerobic Nonspore-Forming Gram-Positive Bacilli: Corynebacterium, Listeria,Erysipelothrix, Actinomycetes,& Related Pathogens 175 Corynebacterium diphtheriae 175 Other Coryneform Bacteria 179 Listeria monocytogenes 180 Erysipelothrix rhusiopathiae 181 Actinomycetes 181 Nocardiosis 182

Actinomycetoma Review Questions

183 183

13. The Staphylococci 185 ReviewQuestions 191 14. The Streptococci 195 Introduction 195 Classification of Streptococci

195

Streptococcus pyogenes 197 Streptococcus agalactiae 202

Groups C & G 202 Group D Streptococci

202

Streptococcusanginosus Group

202

Group N Streptococci 203 Groups E, F, G, H, & K-U Streptococci 203 Viridans Streptococci 203 Nutritionally Variant Streptococci 203 Peptostreptococcus 203 Streptococcuspneumoniae 203 Enterococci 206 Other Catalase-Negative Gram-Positive Cocci 208 ReviewQuestions 209 15. Enteric Gram-Negative Rods (Enterobacteriaceae) 213 Classification 213 Diseases Caused by Enterobacteriaceae Other Than Salmonella & Shigella 217 The Shigellae 220 The Salmonella-Arizona Group 221 Review Questions 225

16. Pseudomonads, Acinetobacters, & Uncommon Gram-Negative Bacteria 227 Pseudomonas aeruginosa 227 Burkholderia pseudomallei 230 Burkholderia mallei 230 Burkholderia cepacia Complex & Burkholderia gladioli 230 Stenotrophomonas maltophilia 231 Other Pseudomonads 231 Actinobacillus 232 Achromobacter & Alcaligenes Ochrobactrum 232

232

Capnocytophaga 232 Cardiobacterium 232 Chromobacteria 232 Eikenella corrodens 232 Chryseobacterium Kingella 233 Moraxella 233 Review Questions

233

17. Vibrios, Campylobacters, Helicobacter, & Associated Bacteria 235 Vibrio cholerae 235 Vibrio parahaemolyticus & Other Vibrios Campylobacter jejuni & Campylobacter coli 239 Campylobacter fetus 240 Other Campylobacters 240 Helicobacter pylori 240 Review Questions 242 18. Haemophilus, Bordetella, Brucella, & Francisella 245 Haemophilus influenzae 245 Haemophilus aegyptius 247 Aggregatibacter aphrophilus 247 Haemophilus ducreyi 247 Other Haemophilus Species 248 Bordetella pertussis 248 Bordetella parapertussis 250 Bordetella bronchiseptica 250 Review Questions 254 257

Yersinia pestis & Plague 257 Yersinia enterocolitica & Yersinia pseudotuberculosis 259 Pasteurella 260 Review Questions 260 20. The Neisseriae

263

Neisseria gonorrhoeae Neisseria meningitidis

21. Infections Caused by Anaerobic Bacteria 273 Anaerobic Bacteria Found in Human Infections 274 Pathogenesis of Anaerobic Infections 277 Immunity in Anaerobic Infections 278 The Polymicrobial Nature of Anaerobic Infections 278 Diagnosis of Anaerobic Infections 278 Treatment of Anaerobic Infections 279 Review Questions 279

22.

232

19. Yersinia & Pasteurella

Other Neisseriae 270 ReviewQuestions 270

263 269

238

Legionellae, Bartonella, & Unusual Bacterial Pathogens 281 Legionellapneumophila & Other Legionellae 281 Bartonella 284 Bacteria That Cause Vaginosis 285 Streptobacillusmoniliformis 285 Calymmatobacterium (Donovania) Granulomatis 286 Whipple Disease 286 Review Questions 286

23. Mycobacteria 289 Mycobacterium tuberculosis 289 Other Mycobacteria 297 Mycobacterium leprae 298 ReviewQuestions 299 24. Spirochetes & Other Spiral Microorganisms 301 Treponemapallidum & Syphilis 301 Diseases Related to Syphilis 304 BorreliaSpecies & Relapsing Fever 305 Borreliaburgdorferi& Lyme Disease 306 Spirillum minor (Spirillum morsus muris) 310 Spirochetes of the Normal Mouth & Mucous Membranes 310 ReviewQuestions 311

25. Mycoplasmas & Cell Wall-Defective Bacteria 313 Mycoplasmas 313 Mycoplasmapneumoniae & Atypical Pneumonias 315 Mycoplasmahominis 316 Ureaplasmaurealyticum 316 Mycoplasmagenitalium 316 Cell Wall-DefectiveBacteria 316 Review Questions 317

vi

26.

Contents

Rickettsia & Ehrlichia 319 General 319 Ehrlichiosis 323 Review Questions 324

Drugs Used Primarily to Treat Mycobacterial Infections 369 ReviewQuestions 371

27. Chlamydiae 327 Trachoma 330 Chlamydia trachomatis:Genital Infections & Inclusion Conjunctivitis 331 Lymphogranuloma venereum 332 Chlamydophilapneumoniae & Respiratory Infections 333 Chlamydiapsittaci & Psittacosis 334 ReviewQuestions 336 28. Antimicrobial Chemotherapy 339 SelectiveToxicity 339 Inhibition of Cell Wall Synthesis 339 Inhibition of Cell Membrane Function 340 Inhibition of Protein Synthesis 341 Inhibition of Nucleic Acid Synthesis 343 Origin of Drug Resistance 343 Cross-Resistance 344 Limitation of Drug Resistance 344 Clinical Implications of Drug Resistance 344 Factors Affecting Antimicrobial Activity 346 Measurement of Antimicrobial Activity 346 Drug-Pathogen Relationships 347 Host - Pathogen Relationships

348

Selection of Antibiotics 348 Dangers of Indiscriminate Use 349 Antimicrobial Drugs Used in Combination 349 Antimicrobial Chemoprophylaxis 350 Penicillins 352 Cephalosporins 358 Other ~-Lactam Drugs 361 Tetracyclines 361 Glycylcyclines 362 Chloramphenicol 362 Erythromycins 363 Clindamycin & Lincomycin 364 Glycopeptides 364 Daptomycin 364 Streptogramins 364 Oxazolidinones 365 Bacitracin 365 Polymyxins 365 Aminoglycosides 365 Quinolones 367 Sulfonamides & Trimethoprim 368 Other Drugs with SpecializedUses 369

S E e T ION

IV

VIROLOGY

373

Janet S. Butel, PhD 29. General Properties ofViruses 373 Terms & Definitions in Virology 373 Evolutionary Origin ofViruses 374 Classification ofViruses 374 PrincipIes ofVirus Structure 378 Chemical Composition of Viruses 380 Cultivation & Assayof Viruses 383 Purification & Identification of Viruses 384 Laboratory Safety 385 Reaction to Physical & Chemical Agents 385 Replication of Viruses: An Overview 386 Genetics of Animal Viruses 391 Natural History (Ecology) & Modes of Transmission of Viruses 393 ReviewQuestions 394 30. Pathogenesis & Control of Viral Diseases PrincipIes of Viral Diseases 397 Pathogenesis of Viral Diseases 398 Prevention & Treatment of Viral Infections 407 ReviewQuestions 413 31. Parvoviruses 417 Properties of Parvoviruses 417 Parvovirus Infections in Humans 418 ReviewQuestions 421 32. Adenoviruses 423 Properties of Adenoviruses 423 Adenovirus Infections in Humans 427 ReviewQuestions 430 33. Herpesviruses 433 Properties of Herpesviruses 433 Herpes Simplex Viruses 437 Varicella-Zoster Virus 442 Cytomegalovirus 445 Epstein-Barr Virus 450 Human Herpesvirus 6 453 Human Herpesvirus 7 453 Human Herpesvirus 8 453 B Virus 453 ReviewQuestions 454

397

34. Poxviruses 457 Properties of Poxviruses 457 Poxvirus Infections in Humans: Vaccinia & Variola 460 Monkeypox Infections 464 Cowpox Infections 465 Buffalopox Infections 465 Orf Virus Infections 465 Molluscum contagiosum 466 Tanapox & YabaMonkey Tumor Poxvirus Infections 468 Review Questions 468 35. Hepatitis Viruses 471 Properties of Hepatitis Viruses 471 Hepatitis Virus Infections in Humans Review Questions 487

476

36. Picornaviruses (Enterovirus & Rhinovirus Groups) 491 Properties of Picornaviruses 491 Polioviruses 494 Coxsackieviruses 497 Other Enteroviruses 500 Enteroviruses in the Environment 501 Parechovirus Group 501 Rhinovirus Group 502 Foot-and-Mouth Disease (Aphthovirus of Cattle) 503 ReviewQuestions 504 37. Reoviruses, Rotaviruses, & Caliciviruses 507 Rotaviruses 508 Reoviruses 512 Orbiviruses & Coltiviruses 512 Caliciviruses 512 Astroviruses 514 ReviewQuestions 515 38. Arthropod-Borne & Rodent-Borne Viral Diseases 517 Togavirus & Flavivirus Encephalitis 519 YellowFever 526 Dengue 528 Bunyavirus Encephalitis 529 Sandfly Fever 530 Rift ValleyFever 530 Colorado Tick Fever 530 Bunyavirus Diseases 531 Arenavirus Diseases 532 Filovirus Diseases 534 ReviewQuestions 536

39. Orthomyxoviruses (Influenza Viruses) 539 Properties of Orthomyxoviruses 539 Influenza Virus Infections in Humans 544 ReviewQuestions 550 40. Paramyxoviruses & Rubella Virus 553 Properties of Paramyxoviruses 553 Parainfluenza Virus Infections 556 Respiratory SyncytialVirus Infections 560 Human Metapneumovirus Infections 562 Mumps Virus Infections 563 Measles (Rubeola) Virus Infections 564 Hendra Virus & Nipah Virus Infections 568 Postnatal Rubella 568 Congenital Rubella Syndrome 570 ReviewQuestions 571 41. Coronaviruses 573 Properties of Coronaviruses 573 Coronavirus Infections in Humans 574 ReviewQuestions 577 42. Rabies, Slow Virus Infections, & Prion Diseases 579 Rabies 579 Borna Disease 585 SlowVirus Infections & Prion Diseases 585 ReviewQuestions 588 43. Human Cancer Viruses 591 General Features ofViral Carcinogenesis 591 Retroviruses 593 Cellular Oncogenes 600 Tumor Suppressor Genes 600 Polyomaviruses 600 Papillomaviruses 602 Adenoviruses 605 Herpesviruses 606 Poxviruses 606 Hepatitis B Virus & Hepatitis C Virus 606 ReviewQuestions 607 44. AIDS & Lentiviruses 609 Properties of Lentiviruses 609 HIV Infections in Humans 613 ReviewQuestions 622 SECTION

V

MYCOLOGY

625

Thomas G. Mitchell, PhD 45.

Medical Mycology

625

General Properties & Classification of Fungi 627

Growth & Isolation of Fungi 630 Superficial Mycoses 630 Cutaneous Mycoses 630 Subcutaneous Mycoses 634 Sporotrichosis 634 Chromoblastomycosis 635 Phaeohyphomycosis 637 Mycetoma 637 Endemic Mycoses 638 Coccidioidomycosis 639 Histoplasmosis 641 Blastomycosis 644 Paracoccidioidomycosis 646 Opportunistic Mycoses 646 Candidiasis 647 Cryptococcosis 649 Aspergillosis 651 Mucormycosis 652 PneumocystisPneumonia 653 Penicilliosis 653 Other Opportunistic Mycoses 654 Antifungal Prophylaxis 654 Hypersensitivity to Fungi 654 Mycotoxins 655 Antifungal Chemotherapy 655 Topical Antifungal Agents 660 ReviewQuestions 661

S E e T ION

VI

PARASITOLOGY

665

¡udy A. Sakanari, PhD, and ¡ames H. McKerrow, MD, PhD

46. Medical Parasitology 665 Giardialamblia (Intestinal Flagellate) 669 Entamoeba histolytica(Intestinal & Tissue Ameba) 670 Other Intestinal Amebae 672 Cryptosporidium (Intestinal Sporozoa) 672 Cyciospora(Intestinal Sporozoa) 673 Trichomonasvaginalis (Genitourinary Flagellate) 673 Blood Flagellates 673 Trypanosoma

brucei rhodesiense & T b gambiense

(Blood Flagellates) 674 Trypanosomacruzi (Blood Flagellate) 675 Leishmania species (Blood Flagellates) 675 Entamoeba histolytica(Tissue Ameba)-See Intestinal Protozoan Infections Section 677

Naegleria fowleri, Acanthamoeba castellanii, & Balamuthia mandrillaris (Free-Living Amebae) 677 Plasmodium Species (Blood Sporozoa) 677 Babesia microti (Blood Sporozoa) 681 Toxoplasma gondii (Tissue Sporozoa) 682 Microsporidia 682 Enterobius vermicularis (Pinworm-Intestinal Nematode) 683 Trichuris trichiura (Whipworm-Intestinal Nematode) 683 Ascaris lumbricoides (Human RoundwormIntestinal Nematode) 684 Ancylostoma

duodenale

& Necator americanus

(Human Hookworms- Intestinal Nematode) 684 Strongyloides

stercoralis (Human

Threadworm-Intestinal & Tissue Nematode) 685 Trichinellaspiralis(Intestinal & Tissue Nematode) 689 Fasciolopsisbuski (Giant Intestinal FlukeIntestinal Trematode) 690 Taeniasaginata (BeefTapeworm- Intestinal Cestode) & Taeniasolium (Pork TapewormIntestinal & Tissue Cestode) 692 Diphyllobothrium latum (Broad Fish Tapeworm-Intestinal Cestode) 692 Hymenolepis nana (DwarfTapewormIntestinal Cestode) 692 Dipylidium caninum (Dog TapewormIntestinal Cestode) 693 Wuchereria

bancrofti & Brugia malayi

(Lymphatic Filariasis- Tissue Nematodes) 693 Onchocerca volvulus (River BlindnessTissue Nematode) 693 Dracunculus medinensis (Guinea WormTissue Nematode) 695 Larva Migrans (Zoonotic Larval Nematode Infections) 695 Clonorchis sinensis (Chinese Liver Fluke), Fasciola hepatica (Sheep Liver Fluke), & Paragonimus westermani (Lung Fluke- Tissue Trematodes) 695 Schistosoma

mansoni,

S japonicum,

&

S haematobium (Blood Flukes) 696 Taeniasolium-Cysticercosis/ Neurocysticercosis 698 Echinococcusgranulosus(Hydatid Cyst) 698 Review Questions

698

Contents

S E e T ION

VII

The Importance of Normal Bacterial & Fungal Flora 714 Laboratory Aids in the Selection of Antimicrobial Therapy 715 Diagnosis of Infection by Anatomic Site 715 Anaerobic Infections 722 Diagnosis of Chlamydial Infections 722 Diagnosis of Viral Infections 724 ReviewQuestions 731

DIAGNOSTIC MEDICAL MICROBIOLOGY & CLINICAL

CORRELATION 703 KarenC. Carroll,MD 47. PrincipIes oí Diagnostic MedicaI MicrobioIogy 703 Communication Between Physician & Laboratory 703 Diagnosis of Bacterial & Fungal Infections

48. Cases & ClinicaI CorreIations 704

lndex

773

735