Medical Microbiology PDF Textbook

I Basic Principles General Aspects of Medical 1 Microbiology Basic Principles of Immunology 2 II Bacteriology General Bacteriology 3...

I Basic Principles General Aspects of Medical 1 Microbiology Basic Principles of Immunology 2 II Bacteriology General Bacteriology 3 Bacteria as Human Pathogens 4 III Mycology General Mycology 5 Fungi as Human Pathogens 6 IV Virology General Virology 7 Viruses as Human Pathogens 8 V Parasitology Protozoa 9 Helminths 10 Arthropods 11 VI Organ System Etiological and Laboratory 12 Infections Diagnostic Summaries in Tabular Form Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. II At a Glance… The book is divided into six main sections. The color-coded reference guide on the first page will help you find what you need. The aspects of each pathogen are covered systematically, using the following order wherever practicable: & Classification & Pathogenesis and Clinical Picture & Localization & Diagnosis & Morphology and Culturing & Therapy & Developmental Cycle & Epidemiology and Prophylaxis & A summary at the beginning of a chapter or section provides a quick over- view of what the main text covers. Students can use the summaries to obtain a quick recapitulation of the main points. & The Main Sections at a Glance a The many colored illustrations serve to clarify complex topics or provide definitive impressions of pathogen morphology. b The header caption above each illustration gives the reader the es- sence of what is shown. c The detailed legends explain the illustrations independently of the main text. Additional information In-depth expositions and supplementary knowledge are framed in boxes inter- spersed throughout the main body of text. The headings outline the topic covered, enabling the reader to decide whether the specific material is needed at the present time. Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. Medical Microbiology Fritz H. Kayser, M.D. Emeritus Professor of Medical Microbiology Institute of Medical Microbiology University of Zurich Zurich, Switzerland Kurt A. Bienz, Ph.D. Emeritus Professor of Virology Institute of Medical Microbiology University of Basle Basle, Switzerland Johannes Eckert, D.V.M. Emeritus Professor of Parasitology Institute of Parasitology University of Zurich Zurich, Switzerland Rolf M. Zinkernagel, M.D. Professor Institute of Experimental Immunology Department of Pathology Zurich, Switzerland 177 illustrations 97 tables Thieme Stuttgart ! New York Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. All rights reserved. Usage subject to terms and conditions of license Library of Congress Cataloging-in- Important note: Medicine is an ever-chan- Publication Data ging science undergoing continual develop- Medizinische Mikrobiologie. English. ment. Research and clinical experience are Medical microbiology / Fritz H. Kayser... continually expanding our knowledge, in [et al.]. p. ; cm. particular our knowledge of proper treat- ISBN 3-13-131991-7 (GTV : alk. paper) – ment and drug therapy. Insofar as this ISBN 1-58890-245-5 (TNY ; alk. paper) book mentions any dosage or application, 1. Medical microbiology. readers may rest assured that the authors, [DNLM: 1. Microbiology. QW 4 M491 editors, and publishers have made every 2005a] I. Kayser, F. H. (Fritz H.) II. Title. effort to ensure that such references are in QR46.M48813 2005 accordance with the state of knowledge 616.9’041–dc22 2004021965 at the time of production of the book. Nevertheless, this does not involve, imply, 1st German edition 1969 or express any guarantee or responsibility on 2nd German edition 1971 the part of the publishers in respect to any 3rd German edition 1974 dosage instructions and forms of applica- 4th German edition 1978 tions stated in the book. Every user is re- 5th German edition 1982 quested to examine carefully the manufac- 6th German edition 1986 turers’ leaflets accompanying each drug and 7th German edition 1989 to check, if necessary in consultation with a 8th German edition 1993 physician or specialist, whether the dosage 9th German edition 1998 schedules mentioned therein or the contra- 1st Greek edition 1995 indications stated by the manufacturers dif- fer from the statements made in the present 1st Italian edition 1996 book. Such examination is particularly im- 1st Japanese edition 1980 portant with drugs that are either rarely 1st Spanish edition 1974 used or have been newly released on the 2nd Spanish edition 1982 market. Every dosage schedule or every 1st Turkish edition 2001 form of application used is entirely at the user’s own risk and responsibility. The This book is an authorized and updated authors and publishers request every user translation of the 10th German edition to report to the publishers any discrepancies published and copyrighted 2001 or inaccuracies noticed. by Georg Thieme Verlag, Stuttgart, Some of the product names, patents, and Germany. Title of the German edition: registered designs referred to in this book Medizinische Mikrobiologie are in fact registered trademarks or proprie- tary names even though specific reference to ª 2005 Georg Thieme Verlag, this fact is not always made in the text. Rüdigerstraße 14, 70469 Stuttgart, Therefore, the appearance of a name without Germany designation as proprietary is not to be con- http://www. thieme.de strued as a representation by the publisher Thieme New York, 333 Seventh Avenue, that it is in the public domain. New York, NY 10001 USA This book, including all parts thereof, is http://www.thieme.com legally protected by copyright. Any use, ex- Cover design: Cyclus, Stuttgart ploitation, or commercialization outside the narrow limits set by copyright legislation, Typesetting by Mitterweger & Partner without the publisher’s consent, is illegal GmbH, 68723 Plankstadt and liable to prosecution. This applies in par- Printed in Germany by Appl, Wemding ticular to photostat reproduction, copying, ISBN 3-13-131991-7 (GTV) mimeographing, preparation of microfilms, ISBN 1-58890-245-5 (TNY) 12345 and electronic data processing and storage. Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. All rights reserved. Usage subject to terms and conditions of license  V Preface Medical Microbiology comprises and integrates the fields of immunology, bacteriology, virology, mycology, and parasitology, each of which has seen considerable independent development in the past few decades. The com- mon bond between them is the focus on the causes of infectious diseases and on the reactions of the host to the pathogens. Although the advent of antibiotics and vaccines has certainly taken the dread out of many infectious diseases, the threat of infection is still a fact of life: New pathogens are con- stantly being discovered; strains of „old“ ones have developed resistance to antibiotics, making therapy more and more difficult; incurable infectious dis- eases (AIDS, rabies) are still with us. The objective of this textbook of medical microbiology is to instill a broad- based knowledge of the etiologic organisms causing disease and the patho- genetic mechanisms leading to clinically manifest infections into its users. This knowledge is a necessary prerequisite for the diagnosis, therapy, and prevention of infectious diseases. This book addresses primarily students of medicine, dentistry, and pharmacy. Beyond this academic purpose, its use- fulness extends to all medical professions and most particularly to physicians working in both clinical and private practice settings. This book makes the vast and complex field of medical microbiology more accessible by the use of four-color graphics and numerous illustrations with detailed explanatory legends. The many tables present knowledge in a cogent and useful form. Most chapters begin with a concise summary, and in-depth and supplementary knowledge are provided in boxes separating them from the main body of text. This textbook has doubtless benefited from the extensive academic teaching and the profound research experience of its authors, all of whom are recognized authorities in their fields. The authors would like to thank all colleagues whose contributions and advice have been a great help and who were so generous with illustration material. The authors are also grateful to the specialists at Thieme Verlag and to the graphic design staff for their cooperation. Zurich, fall of 2004 On behalf of the authors Fritz H. Kayser Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. All rights reserved. Usage subject to terms and conditions of license Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  VII Abbreviations & ABC: antigen-binding cell CCC: covalently closed circular ABS: antigen-binding site (DNA) ADA: adenosine deaminase CD: cluster of differentiation/ ADCC: antibody-dependent cluster determinant cellular cytotoxicity CDR: complementarity-deter- ADE: antibody-dependent mining regions enhancement (of viral CE: cystic echinococcosis infection) CEA: carcinoembryonic antigen AE: alveolar echinococcosis CFA: colonizing factor antigen AFC: antibody-forming cell CFT: complement fixation test AFP: alpha-fetoprotein CFU: colony forming units AIDS: acquired immune CJD: Creutzfeldt-Jakob disease deficiency syndrome CLIP: class II-inhibiting protein ANA: antinuclear antibodies CMI: cell-mediated immunity APC: antigen-presenting cell CMV: cytomegaly virus APO: apoptosis antigen (cytomegalovirus) aPV: acellular pertussis vaccine CNS: central nervous system/ ASL titer: antistreptolysin titer coagulase-negative AZT: azidothymidine staphylococci Con A: concanavalin A & BAL: bronchoalveolar lavage CPE: cytopathic effect BALT: bronchus-associated CPH: chronic persistent lymphoid tissue hepatitis BCG: bacillus Calmette-Guerin CR: cistron region BCGF: B-cell growth factor CSF: colony-stimulating factor Bcl2: B-cell leukemia 2 antigen CTA: cholera toxin A BSE: bovine spongiform ence- CTB: cholera toxin B phalopathy CTL: cytotoxic CD8+ T cell CTX: cholera toxin (element) & C: complement CAH: chronic aggressive & DAF: decay accelerating factor hepatitis DAG: diacyl glycerol CAM: cell adhesion molecules DARC: Duffy antigen receptor CAPD: continuous ambulant for chemokines peritoneal dialysis DC: dendritic cells Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  VIII Abbreviations DHF: dengue hemorrhagic virus fever EPEC: enteropathogenic DHPG: dihydroxy propoxy- E. coli methyl guanine EPS: extracellular polymer D vaccine: substance diphtheria toxoid vaccine ETEC: enterotoxic E. coli DNA: deoxyribonucleic acid EU: European Union DNP: dinitrophenol DR: direct repeats & F factor: fertility factor ds: double-stranded nucleic FA: Freund’s adjuvant acid FACS: fluorescence-activated DSS: dengue shock syndrome cell sorter DTH: delayed type hypersensi- Fas: F antigen tivity FcR: Fc receptor DtxR: diphtheria toxin repressor FDC: follicular dendritic cell FHA: filamentous hemagglutin & EA: early antigen FITC: fluorescein isothiocyanate EAE: experimental allergic FTA-ABS: fluorescent treponemal encephalitis antibody absorption test EAF: EPEC adhesion factor EaggEC: enteroaggregative & G6PDD: glucose-6-phosphate Escherichia coli dehydrogenase deficiency EB: elementary body GAE: granulomatous amebic EBNA: Epstein-Barr nuclear encephalitis antigen gag: group-specific antigen EBV: Epstein-Barr virus GALT: gut-associated lymphoid EDTA: ethylene diamine tetra- tissue acetic acid GC: guanine-cytosine/gas eEF2: eucaryotic elongation chromatography factor 2 GM-CSF: granulocyte-macrophage EF: edema factor in spotted colony-stimulating factor fevers GP: glycoprotein EHEC: enterohemorrhagic GSS: Gerstmann-Sträussler- E. coli Scheinker (syndrome) EIA: enzyme immunoassay GVH: graft-versus-host (reaction) EIEC: enteroinvasive E. coli EITB: enzyme-linked immuno- & H: heavy chain electrotransfer blot HACEK: Haemophilus, Actinoba- ELISA: enzyme-linked immuno- cillus, Cardiobacterium, sorbent assay Eikenella, Kingella EM: electron microscopy HAT: hypoxanthine, EMB: ethambutol aminopterin, thymidine EMCV: encephalomyocarditis Hb: hemoglobin Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  Abbreviations IX HBs: hepatitis B surface antigen & IB: initial body HBV: hepatitis B virus IEP: immunoelectrophoresis HB vaccine: hepatitis B vaccine IFAT: indirect immunofluores- HCC: hepatocellular carcinoma cent antibody test HCV: hepatitis C virus/ IFN: interferon (human corona virus) Ig: immunoglobulin HDCV: human diploid cell IHA: indirect hemagglutina- vaccine tion HDV: hepatitis D virus (I)IF: (indirect) immunofluor- HEV: hepatitis E virus/high escence endothelial venules IL: interleukin Hfr: high frequency of recom- In: integron bination INH: isoniazid (isonicotinic HGE: human granulocytic acid hydrazide) ehrlichiosis IP3: inositol trisphosphate HGV: hepatitis G virus IPV: inactivated polio vaccine HHV: human herpes virus IR: inverted repeats HI: hemagglutination Ir genes: immune response genes inhibition IS: insertion sequence/inter- Hib: Haemophilus influenzae, cistron space type b serovar HIV: human immunodefi- & K cells: killer cells ciency virus & L: light chain HME: human monocytic LA: latex agglutination ehrlichiosis lac operon: lactose operon HPLC: high-pressure liquid LAK: lymphokine-activated chromatography killer cells HPS: hantavirus pulmonary LB: leprosy bacterium syndrome LCA: leukocyte common HRF: homologous restriction antigen factor (also histamine LCM(V): lymphocytic chorio- releasing factor) meningitis (virus) HFRS: hemorrhagic fever with LE: lupus erythematosus renal syndrome LFA: lymphocyte function hsp70: heat shock protein 70 antigen HSV: herpes simplex virus LGL: large granular HTLV: human T cell leukemia lymphocyte virus LIF: leukemia inhibitory HuCV: human calicivirus factor HUS: hemolytic-uremic LL: lepromatous leprosy syndrome LM: light microscopy HVG: host-versus-graft LMC: larva migrans cutanea (reaction) Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  X Abbreviations LMV: larva migrans visceralis MZM: marginal zone macro- LOS: lipo-oligosaccharide phages LPS: lipopolysaccharide LT: heat-labile E. coli entero- & NANB: nonA, nonB hepatitis toxin NCVP: noncapsidic viral protein LTR: long terminal repeats NE: Nephropathica epidemica Nfa: nonfimbrial adhesin & MAC: membrane attack NGU: nongonococcal urethritis complex NIDEP: German study on assess- MAF: macrophage activating ment and prevention of factor nosocomial infections MALT: mucosa-associated NK cells: natural killer cells lymphoid tissue NTM: nontuberculous MBC: minimal bactericidal (atypical) mycobateria concentration (see MOTT) MBP: major basic protein/ NTR: nontranslated region myelin basic protein MCP: membrane cofactor & OC: open circular (DNA) protein OM: opportunistic mycosis M-CSF: macrophage colony- OMP, Omp: outer membrane stimulating factor protein MF: merthiolate-formalin OPV: oral polio vaccine Mf: microfilaria OSP, Osp:outer surface protein MHC: major histocompatibility complex & P: promoter MIC: minimal inhibitory PAE: postantibiotic effect concentration PAIR: puncture, aspiration, in- MIF: migration inhibitory jection, respiration factor/microimmune- PAS: para-aminosalicylic acid/ fluorescence periodic acid-Schiff stain MLC: mixed lymphocyte PAM: primary amebic culture meningoencephalitis MLR: mixed lymphocyte PAP: pyelonephritis-associated reaction pili MMR: live, attenuated, trivalent PBL: peripheral blood lym- measles, mumps, and phocytes rubella vaccine PC: phosphoryl choline/pri- MMTV: murine mammary tumor mary (tuberculous) virus complex, Ghon’s complex MOMP: major outer membrane PCA: passive cutaneous protein anaphylaxis MOTT: mycobacteria other than PCR: polymerase chain reaction TB (see NTM) Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  Abbreviations XI PEG: polyethylene glycol RNA: ribonucleic acid PFC: plaque-forming cell RNP: ribonucleoprotein PHA: phytohemagglutinin RS: respiratory syncytial PI: pathogenicity island virus p.i.: post infection RT: reverse transcriptase PIP2: phosphatidylinositol RT-PCR: reverse transcriptase- bisphosphate polymerase chain PKC: protein kinase C reaction PLC: phospholipase C RTI: respiratory tract infection PMA: pokeweed mitogen RVF: Rift Valley fever PML: progressive multifocal leukoencephalopathy & SAF: sodium acetate-acetic PMN: polymorphonuclear neu- acid-formalin trophilic granulocytes SALT: skin-associated lymphoid PNP: purine nucleoside phos- tissue phorylase SCF: stem cell factor PPD: purified protein derivative SCID: severe combined immuno- PRP: polyribosylribitol phos- deficiency disease phate SDS: sodium (Na+) dodecyl PrP: prion protein sulfate Ptx: pertussis toxin SEA-E: staphylococcal entero- PZA: pyrazinamide toxins A-E SEM: scanning electron micro- & QBC: quantitative buffy coat scopy analysis SEP: sepsis & R: SEPEC: septic E. coli pathovar rubella vaccine SFT: Sabin-Feldman test RAST: radioallergosorbent test SLE: systemic lupus erythe- RES: reticuloendothelial matosus system SPE: streptococcal pyrogenic RF: rheumatoid factor exotoxin RFFIT: rapid fluorescent focus SRBC: sheep red blood cells inhibition test SRSV: small round-structured Rh antigen: rhesus antigen virus RIA: radioimmunoassay ss: single-stranded (nucleic RIBA: recombinant immuno- acids) blot assay SSME: spring-summer meningo- RIG: rabies immunoglobulin encephalitis RIST: radioimmunosorbent SSPE: subacute sclerosing test panencephalitis RMP: rifampicin ST: heat-stable E. coli entero- RMSF: Rocky Mountain spotted toxin fever Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  XII Abbreviations sp.: species Tra: transfer spp.: species (plural) TSE: transmissible spongiform SV: simian virus encephalopathy SWI: surgical wound infection TSS: toxic shock syndrome TSST-1: toxic shock syndrome & TATA: tumor-associated trans- toxin-1 plantation antigen TU: tuberculin units TB: tuberculosis bacterium Tc: cytotoxic T cell & UPEC: uropathogenic E. coli TCGF: T cell growth factor UTI: urinary tract infection TCP: toxin coregulated pili TCR: T cell receptor & VacA: vacuolating cytotoxin Td: tetanus/low-dose var.: variety diphtheria toxoids VCA: viral capsid antigen T-dep: thymus dependent VCAM: vascular cell adhesion antigens molecule T-DTH: delayed type hyper- VDRL: Venereal Disease sensitivity (T cells) Research Laboratory TEM: transmission electron VLA: very late antigen microscopy vmp: variable major protein Th, TH: T helper cell VPv: viral protein T-ind: thymus-independent VPg: genome-linked viral antigens protein TL: tuberculoid leprosy VSA: variant surface antigen TME: transmissible mink VSV: vesicular stomatitis virus encephalopathy VTEC: verocytotoxin-producing Tn: transposon E. coli TNF: tumor necrosis factor VZV: varicella zoster virus TPHA: Treponema pallidum hemagglutination assay & WB: Western blot TPI test: Treponema pallidum WHO: World Health Organiza- immobilization test tion TPPA: Treponema pallidum particle agglutination assay Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  XIII Contents I Basic Principles of Medical Microbiology and Immunology 1 General Aspects of Medical Microbiology F. H. Kayser 2 The History of Infectious Diseases.................................. 2 The Past..................................................... 2 The Henle–Koch Postulates................................ 3 The Present................................................. 3 Pathogens........................................................... 4 Subcellular Infectious Entities............................. 4 Prokaryotic and Eukaryotic Microorganisms.............. 4 Bacteria..................................................... 5 Fungi and Protozoa......................................... 6 Animals..................................................... 7 Host–Pathogen Interactions......................................... 7 Basic Terminology of Infectiology.......................... 8 Determinants of Bacterial Pathogenicity and Virulence... 8 Adhesion................................................ 11 Invasion and Spread.................................... 12 Strategies against Nonspecific Immunity.............. 12 Strategies against Specific Immunity.................. 13 Clinical Disease......................................... 15 Regulation of Bacterial Virulence...................... 18 The Genetics of Bacterial Pathogenicity............... 20 Defenses against Infection................................. 21 Nonspecific Defense Mechanisms...................... 21 Specific Defense Mechanisms.......................... 23 Defects in Immune Defenses........................... 24 Normal Flora................................................ 24 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. XIV Contents General Epidemiology........................................... 25 Epidemiological Terminology.............................. 26 Transmission, Sources of Infection........................ 26 Transmission.......................................... 26 Sources of Infection.................................... 30 The Fight against Infectious Diseases.................... 31 Legislation........................................... 31 Exposure Prophylaxis................................... 31 Immunization Prophylaxis............................. 31 Principles of Sterilization and Disinfection...................................... 34 Terms and General Introduction............................. 34 Terms.................................................. 34 The Kinetics of Pathogen.. Killing.............................. 35 Mechanisms of Action...................... 36 Physical Methods of Sterilization and Disinfection............. 37 Heat.................................................... 37 Radiation............................................... 38 Filtration............................................... 38 Chemical Methods of Sterilization and Disinfection........ 39 Practical Disinfection...................................... 40 2 Basic Principles of Immunology R. M. Zinkernagel 43 Introduction........................................................ 43 The Immunological Apparatus............................................ 45 The B-Cell System................................................ 48 Immunoglobulin Structure................................. 50 Diversity within the Variable Domains of the Immunoglobulins......................................... 53 The Different Classes of Immunoglobulins................ 54 The T-Cell System............................................... 57 T-Cell Receptors (TCR) and Accessory Molecules........ 57 T-Cell Specificity and the Major Histocompatibility Complex (MHC).......................................... 58 T-Cell Maturation: Positive and Negative Selection....... 63 T-Cell Subpopulations.................................... 64 Immune Responses and Effector Mechanisms.................... 66 B Cells..................................................... 67 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  Contents XV B-Cell Epitopes and B-Cell Proliferation............... 67 Monoclonal Antibodies................................. 69 T-Independent B Cell Responses....................... 69 T Cells....................................................... 71 T-Cell Activation........................................ 71 T-Cell Activation by Superantigens.................... 72 Interactions between Cells of the Immune System....... 72 T Helper Cells (CD4+ T Cells) and T-B Cell Collaboration........................................... 72 Subpopulations of T Helper Cells...................... 75 Cytotoxic T Cells (CD8+ T Cells)........................ 75 Cytokines (Interleukins) and Adhesion................ 77 Antibody-Dependent Cellular Immunity and Natural Killer Cells..................................... 85 Humoral, Antibody-Dependent Effector Mechanisms............................................ 85 The Complement System................................... 86 Immunological Cell Death.................................. 90 Immunological Tolerance........................................... 90 T-Cell Tolerance............................................ 90 B-Cell Tolerance............................................ 93 Immunological Memory............................................ 94 B-Cell Memory............................................. 96 T-Cell Memory.............................................. 98 Immune Defenses against Infection and Tumor Immunity......... 99 General Rules Applying to Infection Defenses............ 100 Immune Protection and Immunopathology.............. 103 Influence of Prophylactic Immunization on the Immune Defenses..................................... 106 Tumor Immunity.......................................... 107 The Pathological Immune Response................................ 108 Type I: IgE-Triggered Anaphylaxis........................ 108 Type II: Cytotoxic Humoral Immune Responses.......... 109 Autoantibody Responses.............................. 110 Anti-blood Group Antibody Reactions................ 111 Type III: Diseases Caused by Immune Complexes........ 113 Type IV: Cell-mediated Immunopathology............... 114 Transplantation Immunity......................................... 115 Immune Defects and Immune Response Modulation.............. 117 Immune Defects.......................................... 118 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. XVI Contents Immunoregulation........................................ 118 Immunostimulation................................... 119 Immunosuppression................................... 120 Adaptive Immunotherapy............................. 120 Immunological Test Methods...................................... 121 Antigen and Antibody Assays............................. 121 Immunoprecipitation in Liquids and Gels............ 121 Agglutination Reactions............................... 123 Complement Fixation Test (CFT)...................... 125 Direct and Indirect Immunofluorescence............. 125 Radioimmunological and Enzyme Immunological Tests.................................. 128 In-Vitro Cellular Immunity Reactions.................... 129 Isolation of Lymphocytes.............................. 129 Lymphocyte Function Tests........................... 132 II Bacteriology 3 General Bacteriology F. H. Kayser 146 The Morphology and Fine Structure of Bacteria................... 146 Bacterial Forms............................................ 146 Fine Structures of Bacteria................................ 148 Nucleoid (Nucleus Equivalent) and Plasmids......... 148 Cytoplasm............................................. 151 The Cytoplasmic Membrane.......................... 151 Cell Wall............................................... 152 Capsule................................................ 157 Flagella................................................. 157 Attachment Pili (Fimbriae), Conjugation Pili......... 158 Biofilm................................................. 158 Bacterial Spores........................................ 159 The Physiology of Metabolism and Growth in Bacteria............ 160 Bacterial Metabolism...................................... 160 Types of Metabolism.................................. 160 Catabolic Reactions.................................... 161 Anabolic Reactions.................................... 163 Metabolic Regulation.................................. 164 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  Contents XVII Growth and Culturing of Bacteria........................ 164 Nutrients............................................... 164 Growth and Cell Death................................ 165 The Molecular Basis of Bacterial Genetics......................... 166 The Structure of Bacterial DNA........................... 167 DNA Replication........................................... 168 Transcription and Translation............................. 168 Regulation of Gene Expression........................... 169 The Genetic Variability of Bacteria................................ 170 Molecular Mechanisms of Genetic Variability............ 171 Spontaneous Mutation................................ 171 Recombination......................................... 171 Intercellular Mechanisms of Genetic Variability.......... 174 Transformation........................................ 174 Transduction........................................... 174 Conjugation............................................ 175 Restriction, Modification, and Gene Cloning......... 177 Bacteriophages..................................................... 182 Definition.................................................. 182 Morphology................................................ 182 Composition............................................... 183 Reproduction.............................................. 184 Lysogeny................................................... 186 The Principles of Antibiotic Therapy............................... 187 Definitions................................................. 187 Spectrum of Action........................................ 196 Efficacy.................................................... 196 Mechanisms of Action..................................... 197 Pharmacokinetics.......................................... 200 Side Effects................................................ 200 The Problem of Resistance................................ 201 Definitions............................................. 201 Incidence, Significance................................ 201 Resistance Mechanisms............................... 202 Evolution of Resistance to Anti-Infective Agents..... 203 Resistance Tests........................................ 204 Combination Therapy..................................... 205 Chemoprophylaxis......................................... 206 Immunomodulators....................................... 207 Laboratory Diagnosis.............................................. 207 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. XVIII Contents Preconditions, General Methods, Evaluation............. 208 Preconditions.......................................... 208 General Methods and Evaluation..................... 208 Sampling and Transport of Test Material................. 208 Microscopy................................................ 211 Culturing Methods........................................ 212 Identification of Bacteria.................................. 214 Molecular Methods........................................ 216 Direct Detection of Bacterial Antigens.................... 217 Diagnostic Animal Tests................................... 217 Bacteriological Laboratory Safety......................... 217 Taxonomy and Overview of Human Pathogenic Bacteria.......... 218 Classification............................................... 218 Nomenclature............................................. 228 4 Bacteria as Human Pathogens F. H. Kayser 229 Staphylococcus..................................................... 229 Staphylococcus aureus................................ 230 Coagulase-Negative Staphylococci (CNS)............. 234 Streptococcus and Enterococcus................................... 234 Streptococcus pyogenes (A Streptococci)............. 237 Streptococcus pneumoniae (Pneumococci)........... 240 Streptococcus agalactiae (B Streptococci)............. 242 Oral Streptococci...................................... 242 Enterococcus (Enterococci)............................ 243 Gram-Positive, Anaerobic Cocci.................................... 244 Bacillus............................................................. 244 Bacillus anthracis (Anthrax)........................... 245 Clostridium........................................................ 246 The Pathogens That Cause Gas Gangrene (Clostridial Myonecrosis) and Anaerobic Cellulitis... 246 Clostridium tetani (Tetanus).......................... 248 Clostridium botulinum (Botulism).................... 250 Clostridium difficile (Pseudomembranous Colitis)... 251 Listeria, Erysipelothrix, and Gardnerella........................... 251 Listeria monocytogenes............................... 252 Erysipelothrix rhusiopathiae.......................... 253 Gardnerella vaginalis.................................. 254 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  Contents XIX Corynebacterium, Actinomyces, Other Gram-Positive Rod Bacteria 254 Corynebacterium diphtheriae (Diphtheria)........... 255 Actinomyces........................................... 258 Other Gram-Positive Rod Bacteria.................... 260 Mycobacterium.................................................... 262 Tuberculosis Bacteria (TB)............................. 263 Leprosy Bacteria (LB).................................. 269 Nontuberculous Mycobacteria (NTM)................. 271 Nocardia........................................................... 272 Neisseria, Moraxella, and Acinetobacter........................... 273 Neisseria gonorrheae (Gonorrhea).................... 274 Neisseria meningitidis (Meningitis, Sepsis)........... 276 Moraxella and Acinetobacter.......................... 278 Enterobacteriaceae, Overview...................................... 278 Salmonella (Gastroenteritis, Typhoid Fever, Paratyphoid Fever)... 282 Shigella (Bacterial Dysentery)..................................... 287 Yersinia (Plague, Enteritis)......................................... 289 Yersinia pestis......................................... 289 Yersinia enterocolitica and Yersinia pseudotuberculosis.................................... 290 Escherichia coli.................................................... 292 Opportunistic Enterobacteriaceae.................................. 295 Vibrio, Aeromonas, and Plesiomonas.............................. 296 Vibrio cholerae (Cholera).............................. 297 Other Vibrio Bacteria.................................. 300 Aeromonas and Plesiomonas.......................... 300 Haemophilus and Pasteurella...................................... 300 Haemophilus influenzae.............................. 301 Haemophilus ducreyi and Haemophilus aegyptius.. 303 Pasteurella............................................. 303 Gram-Negative Rod Bacteria with Low Pathogenic Potential...... 304 Campylobacter, Helicobacter, Spirillum............................ 306 Campylobacter......................................... 306 Helicobacter pylori.................................... 307 Spirillum minus....................................... 308 Pseudomonas, Stenotrophomonas, Burkholderia................... 308 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. XX Contents Pseudomonas aeruginosa............................. 309 Other Pseudomonas species, Stenotrophomonas and Burkholderia...................................... 310 Legionella (Legionnaire’s Disease)................................. 311 Brucella, Bordetella, Francisella.................................... 313 Brucella (Brucellosis, Bang’s Disease)................. 313 Bordetella (Whooping Cough, Pertussis)............. 315 Francisella tularensis (Tularemia)..................... 316 Gram-Negative Anaerobes......................................... 317 Treponema (Syphilis, Yaws, Pinta)................................. 320 Treponema pallidum, subsp. pallidum (Syphilis)..... 320 Treponema pallidum, subsp. endemicum (Nonvenereal Syphilis)................................ 323 Treponema pallidum, subsp. pertenue (Yaws)........ 323 Treponema carateum (Pinta).......................... 323 Borrelia (Relapsing Fever, Lyme Disease).......................... 324 Borrelia That Cause Relapsing Fevers................. 324 Borrelia burgdorferi (Lyme Disease).................. 326 Leptospira (Leptospirosis, Weil Disease)........................... 328 Rickettsia, Coxiella, Orientia, and Ehrlichia (Typhus, Spotted Fever, Q Fever, Ehrlichioses)...................... 330 Bartonella and Afipia.............................................. 334 Bartonella.............................................. 334 Afipia felis............................................. 335 Chlamydia......................................................... 335 Overview and General Characteristics of Chlamydiae......................................... 336 Chlamydia psittaci (Ornithosis, Psittacosis)........... 337 Chlamydia trachomatis (Trachoma, Lymphogranuloma venereum)........... 338 Chlamydia pneumoniae............................... 339 Mycoplasma....................................................... 340 Nosocomial Infections.............................................. 342 Definition.............................................. 342 Pathogens, Infections, Frequency..................... 342 Sources of Infection, Transmission Pathways......... 345 Control................................................. 345 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  Contents XXI III Mycology 5 General Mycology F. H. Kayser 348 General Characteristics of Fungi................................... 348 Definition and Taxonomy................................. 348 Morphology................................................ 349 Metabolism................................................ 351 Reproduction in Fungi..................................... 351 General Aspects of Fungal Disease................................. 352 Fungal Allergies and Fungal Toxicoses.................... 352 Mycogenic Allergies................................... 352 Mycotoxicoses......................................... 353 Mycoses.................................................... 353 Host-Pathogen Interactions........................... 353 Diagnosis.............................................. 356 Therapy................................................ 356 6 Fungi as Human Pathogens F. H. Kayser 358 Primary Mycoses................................................... 358 Histoplasma capsulatum (Histoplasmosis)........... 358 Coccidioides immitis (Coccidioidomycosis)........... 360 Blastomyces dermatitidis (North American Blastomycosis)...................... 361 Paracoccidioides brasiliensis (South American Blastomycosis)......................................... 361 Opportunistic Mycoses............................................. 362 Candida (Soor)......................................... 362 Aspergillus (Aspergillosis)............................. 364 Cryptococcus neoformans (Cryptococcosis).......... 366 Mucor, Absidia, Rhizopus (Mucormycoses)........... 367 Phaeohyphomycetes, Hyalohyphomycetes, Opportunistic Yeasts, Penicillium marneffei.......... 369 Pneumocystis carinii (Pneumocystosis)............... 370 Subcutaneous Mycoses............................................. 372 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. All rights reserved. Usage subject to terms and conditions of license XXII Contents Cutaneous Mycoses................................................ 372 Dermatophytes (Dermatomycoses or Dermatophytoses)..................................... 372 Other Cutaneous Mycoses............................. 374 IV Virology 7 General Virology K. A. Bienz 376 Definition.......................................................... 376 Morphology and Structure......................................... 377 Classification....................................................... 380 Replication......................................................... 381 Viral Protein Synthesis............................................. 387 Genetics............................................................ 389 Host-Cell Reactions................................................ 392 Cell Destruction (Cytocidal Infection, Necrosis).......... 392 Virus Replication without Cell Destruction (Noncytocidal Infection)................................... 393 Latent Infection............................................ 394 Tumor Transformation.................................... 394 Carcinogenic Retroviruses (“Oncoviruses”)........... 394 DNA Tumor Viruses................................... 396 Pathogenesis....................................................... 396 Defense Mechanisms............................................... 399 Nonspecific Immune Defenses............................ 400 Specific Immune Defenses................................ 401 Prevention......................................................... 402 Chemotherapy..................................................... 404 Laboratory Diagnosis.............................................. 405 Virus Isolation by Culturing............................... 406 Direct Virus Detection..................................... 408 Virus Detection Following Biochemical Amplification.......................................... 409 Serodiagnosis.............................................. 411 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. All rights reserved. Usage subject to terms and conditions of license  Contents XXIII 8 Viruses as Human Pathogens K. A. Bienz 412 DNA Viruses........................................................ 412 Viruses with Single-Stranded DNA Genomes............. 412 Parvoviruses........................................... 412 Viruses with Double-Stranded DNA Genomes........... 413 Papillomaviruses....................................... 413 Polyomaviruses........................................ 415 Adenoviruses.......................................... 416 Herpesviruses.......................................... 418 Poxviruses............................................. 426 Hepadnaviruses: Hepatitis B Virus and Hepatitis D Virus...................................... 429 RNA Viruses........................................................ 434 Viruses with Single-Stranded RNA Genomes, Sense-Strand Orientation................................. 434 Picornaviruses......................................... 434 Astrovirus and Calicivirus; Hepatitis E................ 438 Astroviruses............................................ 439 Caliciviruses........................................... 439 Hepatitis E Virus....................................... 440 Togaviruses............................................ 440 Flaviviruses............................................ 442 Coronaviruses.......................................... 446 Retroviruses........................................... 448 Human Immune Deficiency Virus (HIV).............. 451 Viruses with Double-Stranded RNA Genomes............ 455 Reoviruses............................................. 455 Viruses with Single-Stranded RNA Genomes, Antisense-Strand Orientation............................. 457 Orthomyxoviruses..................................... 458 Bunyaviruses........................................... 460 Arenaviruses........................................... 462 Paramyxoviruses....................................... 464 Rhabdoviruses......................................... 467 Filoviruses (Marburg and Ebola Viruses)............. 471 Subviral Pathogens: Viroids and Prions............................ 472 Viroids................................................. 472 Prions.................................................. 473 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. XXIV Contents V Parasitology 9 Protozoa J. Eckert 476 Giardia intestinalis................................................. 478 Trichomonas vaginalis............................................. 481 Trypanosoma...................................................... 483 Leishmania......................................................... 493 Entamoeba histolytica and Other Intestinal Amebas.............. 499 Naegleria, Acanthamoeba, and Balamuthia....................... 507 Toxoplasma gondii................................................. 508 Isospora............................................................ 515 Cyclospora cayetanensis........................................... 515 Sarcocystis......................................................... 516 Cryptosporidium................................................... 517 Plasmodium........................................................ 520 Babesia............................................................. 538 Microspora......................................................... 538 Balantidium coli................................................... 542 10 Helminths J. Eckert 543 Plathelmintha (syn. Platyhelminthes)............................. 546 Trematoda (Flukes)........................................ 546 Schistosoma (Blood Flukes)........................... 546 Fasciola species........................................ 555 Dicrocoelium.......................................... 557 Opisthorchis and Clonorchis (Cat Liver Fluke and Chinese Liver Fluke)................................... 557 Paragonimus (Lung Flukes)........................... 558 Cestoda (Tapeworms)..................................... 560 Taenia Species......................................... 560 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  Contents XXV Echinococcus.......................................... 565 Hymenolepis........................................... 575 Diphyllobothrium...................................... 575 Nematoda (Roundworms)......................................... 576 Intestinal Nematodes...................................... 576 Ascaris lumbricoides (Large Roundworm)............ 577 Trichuris trichiura (Whipworm)...................... 579 Ancylostoma and Necator (Hookworms)............. 580 Strongyloides.......................................... 582 Enterobius............................................. 585 Nematodal Infections of Tissues and the Vascular System 587 Filarioidea (Filariae)................................... 587 Wuchereria bancrofti and Brugia Species............ 588 Loa..................................................... 593 Mansonella Species.................................... 593 Onchocerca............................................ 594 Trichinella............................................. 597 Infections Caused by Nematodal Larvae.................. 601 Larva Migrans Externa or Cutaneous Larva Migrans (“Creeping Eruption”)........................ 602 Larva Migrans Interna or Visceral Larva Migrans................................ 602 11 Arthropods J. Eckert 606 Arachnida.......................................................... 607 Ticks (Ixodida)......................................... 607 Mites................................................... 610 Insects.............................................................. 612 Lice (Anoplura)........................................ 612 Bugs (Heteroptera).................................... 616 Mosquitoes and Flies (Diptera: Nematocera and Brachycera)............................................ 616 Fleas (Siphonatera).................................... 618 Appendix to Chapters 9 – 11...................................... 621 Shipment of Materials............................................. 621 Stool................................................... 621 Blood................................................... 622 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license. All rights reserved. Usage subject to terms and conditions of license XXVI Contents Serum.................................................. 623 Cerebrospinal Fluid.................................... 623 Bronchial Specimens.................................. 623 Urine................................................... 623 Cultivation......................................................... 623 Material for Polymerase Chain Reaction........................... 624 Tissue Specimens and Parasites....................... 624 Immunodiagnostic and Molecular Techniques..................... 624 VI Organ System Infections 12 Etiological and Laboratory Diagnostic Summaries in Tabular Form F. H. Kayser, J. Eckert, K. A. Bienz 630 Upper Respiratory Tract........................................... 630 Lower Respiratory Tract........................................... 632 Urogenital Tract.................................................... 635 Genital Tract (Venereal Diseases).................................. 637 Gastrointestinal Tract.............................................. 638 Digestive Glands and Peritoneum.................................. 641 Nervous System.................................................... 644 Cardiovascular system............................................. 647 Hematopoietic and Lymphoreticular System....................... 648 Skin and Subcutaneous Connective Tissue (Local or Systemic Infections with Mainly Cutaneous Manifestation)................. 650 Bone, Joints, and Muscles.......................................... 653 Eyes and ears...................................................... 655 Literature.......................................................... 659 Medical Microbiology and the Internet......................... 661 Index.............................................................. 663 Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  I Basic Principles of Medical Microbiologie and Immunology F Boehringer Ingelheim International GmbH Dr. Karl Thomae GmbH Macrophage hunting bacteria Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  2 1 1 General Aspects of Medical Microbiology F. H. Kayser & Infectious diseases are caused by subcellular infectious entities (prions, viruses), prokaryotic bacteria, eukaryotic fungi and protozoans, metazoan an- imals, such as parasitic worms (helminths), and some arthropods. Definitive proof that one of these factors is the cause of a given infection is demon- strated by fulfillment of the three Henle-Koch postulates. For technical rea- sons, a number of infections cannot fulfill the postulates in their strictest sense as formulated by R. Koch, in these cases a modified form of the pos- tulates is applied. & The History of Infectious Diseases The Past Infectious diseases have been known for thousands of years, although accu- rate information on their etiology has only been available for about a century. In the medical teachings of Hippocrates, the cause of infections occurring fre- quently in a certain locality or during a certain period (epidemics) was sought in “changes” in the air according to the theory of miasmas. This concept, still reflected in terms such as “swamp fever” or “malaria,” was the predominant academic opinion until the end of the 19th century, despite the fact that the Dutch cloth merchant A. van Leeuwenhoek had seen and described bacteria as early as the 17th century, using a microscope he built himself with a single convex lens and a very short focal length. At the time, general acceptance of the notion of “spontaneous generation”—creation of life from dead organic material—stood in the way of implicating the bacteria found in the corpses of infection victims as the cause of the deadly diseases. It was not until Pas- teur disproved the doctrine of spontaneous generation in the second half of the 19th century that a new way of thinking became possible. By the end of that century, microorganisms had been identified as the causal agents in many familiar diseases by applying the Henle-Koch postulates formulated by R. Koch in 1890. Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  The History of Infectious Diseases 3 The Henle–Koch Postulates 1 The postulates can be freely formulated as follows: & The microorganism must be found under conditions corresponding to the pathological changes and clinical course of the disease in question. & It must be possible to cause an identical (human) or similar (animal) dis- ease with pure cultures of the pathogen. & The pathogen must not occur within the framework of other diseases as an “accidental parasite.” These postulates are still used today to confirm the cause of an infectious dis- ease. However, the fact that these conditions are not met does not necessarily exclude a contribution to disease etiology by a pathogen found in context. In particular, many infections caused by subcellular entities do not fulfill the postulates in their classic form. The Present The frequency and deadliness of infectious diseases throughout thousands of years of human history have kept them at the focus of medical science. The development of effective preventive and therapeutic measures in recent dec- ades has diminished, and sometimes eliminated entirely, the grim epidemics of smallpox, plague, spotted fever, diphtheria, and other such contagions. To- day we have specific drug treatments for many infectious diseases. As a result of these developments, the attention of medical researchers was diverted to other fields: it seemed we had tamed the infectious diseases. Recent years have proved this assumption false. Previously unknown pathogens causing new diseases are being found and familiar organisms have demonstrated an ability to evolve new forms and reassert themselves. The origins of this reversal are many and complex: human behavior has changed, particularly in terms of mobility and nutrition. Further contributory factors were the in- troduction of invasive and aggressive medical therapies, neglect of estab- lished methods of infection control and, of course, the ability of pathogens to make full use of their specific genetic variability to adapt to changing con- ditions. The upshot is that physicians in particular, as well as other medical professionals and staff, urgently require a basic knowledge of the pathogens involved and the genesis of infectious diseases if they are to respond effec- tively to this dynamism in the field of infectiology. The aim of this textbook is to impart these essentials to them. Table 1.1 provides an overview of the causes of human infectious diseases. Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  4 1 General Aspects of Medical Microbiology Table 1.1 Human Pathogens 1 Subcellular Prokaryotic Eukaryotic Animals biological entities microorganisms microorganisms Prions Chlamydiae Fungi Helminths (infection proteins) (0.3–1 lm) (yeasts 5–10 lm, (parasitic worms) size of mold fungi indeterminable) Viruses Rickettsiae Protozoa Arthropods (20–200 nm) (0.3–1 lm) (1–150 lm) Mycoplasmas Classic bacteria (1–5 lm) Pathogens Subcellular Infectious Entities & Prions (proteinaceous infectious particles). The evidence indicates that prions are protein molecules that cause degenerative central nervous system (CNS) diseases such as Creutzfeldt-Jakob disease, kuru, scrapie in sheep, and bovine spongiform encephalopathy (BSE) (general term: transmissible spon- giform encephalopathies [TSE]). Viruses. Ultramicroscopic, obligate intracellular parasites that: — contain only one type of nucleic acid, either DNA or RNA, — possess no enzymatic energy-producing system and no protein-synthe- sizing apparatus, and — force infected host cells to synthesize virus particles. Prokaryotic and Eukaryotic Microorganisms According to a proposal by Woese that has been gaining general acceptance in recent years, the world of living things is classified in the three domains bac- teria, archaea, and eucarya. In this system, each domain is subdivided into Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  Pathogens 5 kingdoms. Pathogenic microorganisms are found in the domains bacteria and eucarya. 1 Bacteria, Archaea, Eucarya Bacteria. This domain includes the kingdom of the heterotrophic eubacteria and includes all human pathogen bacteria. The other kingdoms, for instance that of the photosynthetic cyanobacteria, are not pathogenic. It is estimated that bacterial spe- cies on Earth number in the hundreds of thousands, of which only about 5500 have been discovered and described in detail. Archaea. This domain includes forms that live under extreme environmental con- ditions, including thermophilic, hyperthermophilic, halophilic, and methanogenic microorganisms. The earlier term for the archaea was archaebacteria (ancient bac- teria), and they are indeed a kind of living fossil. Thermophilic archaea thrive mainly in warm, moist biotopes such as the hot springs at the top of geothermal vents. The hyperthermophilic archaea, a more recent discovery, live near deep-sea volcanic plumes at temperatures exceeding 100 8C. Eucarya. This domain includes all life forms with cells possessing a genuine nucleus. The plant and animal kingdoms (animales and plantales) are all eukaryotic life forms. Pathogenic eukaryotic microorganisms include fungal and protozoan spe- cies. Table 1.2 lists the main differences between prokaryotic (bacteria and ar- chaea) and eukaryotic pathogens. Bacteria & Classic bacteria. These organisms reproduce asexually by binary trans- verse fission. They do not possess the nucleus typical of eucarya. The cell walls of these organisms are rigid (with some exceptions, e.g., the mycoplas- ma). & Chlamydiae. These organisms are obligate intracellular parasites that are able to reproduce in certain human cells only and are found in two stages: the infectious, nonreproductive particles called elementary bodies (0.3 lm) and the noninfectious, intracytoplasmic, reproductive forms known as initial (or reticulate) bodies (1 lm). & Rickettsiae. These organisms are obligate intracellular parasites, rod- shaped to coccoid, that reproduce by binary transverse fission. The diameter of the individual cell is from 0.3–1 lm. Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  6 1 General Aspects of Medical Microbiology Table 1.2 Characteristics of Prokaryotic (Eubacteria) and Eukaryotic (Fungi, 1 Protozoans) Microorganisms Characteristic Prokaryotes Eukaryotes (bacteria) (fungi, protozoans) Nuclear structure Circular DNA molecule not Complex of DNA and basic covered with proteins proteins Localization of Dense tangle of DNA in cyto- In nucleus surrounded by nuclear structure plasm; no nuclear membrane; nuclear membrane nucleoid or nuclear equivalent DNA Nucleoid and plasmids In nucleus and in mitochon- dria Cytoplasm No mitochondria and no endo- Mitochondria and endoplas- plasmic reticulum, 70S ribo- mic reticulum, 80S ribosomes somes Cell wall Usually rigid wall with murein Present only in fungi: glucans, layer; exception: mycoplasmas mannans, chitin, chitosan, cellulose Reproduction Asexual, by binary transverse In most cases sexual, possibly fission asexual & Mycoplasmas. Mycoplasmas are bacteria without rigid cell walls. They are found in a wide variety of forms, the most common being the coccoid cell (0.3–0.8 lm). Threadlike forms also occur in various lengths. Fungi and Protozoa & Fungi. Fungi (Mycophyta) are nonmotile eukaryotes with rigid cell walls and a classic cell nucleus. They contain no photosynthetic pigments and are carbon heterotrophic, that is, they utilize various organic nutrient substrates (in contrast to carbon autotrophic plants). Of more than 50 000 fungal spe- cies, only about 300 are known to be human pathogens. Most fungal infec- tions occur as a result of weakened host immune defenses. & Protozoa. Protozoa are microorganisms in various sizes and forms that may be free-living or parasitic. They possess a nucleus containing chromo- somes and organelles such as mitochondria (lacking in some cases), an en- Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  Host–Pathogen Interactions 7 doplasmic reticulum, pseudopods, flagella, cilia, kinetoplasts, etc. Many para- sitic protozoa are transmitted by arthropods, whereby multiplication and 1 transformation into the infectious stage take place in the vector. Animals & Helminths. Parasitic worms belong to the animal kingdom. These are metazoan organisms with highly differentiated structures. Medically signif- icant groups include the trematodes (flukes or flatworms), cestodes (tape- worms), and nematodes (roundworms). & Arthropods. These animals are characterized by an external chitin skele- ton, segmented bodies, jointed legs, special mouthparts, and other specific features. Their role as direct causative agents of diseases is a minor one (mites, for instance, cause scabies) as compared to their role as vectors trans- mitting viruses, bacteria, protozoa, and helminths. Host–Pathogen Interactions & The factors determining the genesis, clinical picture and outcome of an infection include complex relationships between the host and invading or- ganisms that differ widely depending on the pathogen involved. Despite this variability, a number of general principles apply to the interactions be- tween the invading pathogen with its aggression factors and the host with its defenses. Since the pathogenesis of bacterial infectious diseases has been re- searched very thoroughly, the following summary is based on the host–in- vader interactions seen in this type of infection. The determinants of bacterial pathogenicity and virulence can be outlined as follows: & Adhesion to host cells (adhesins). & Breaching of host anatomical barriers (invasins) and colonization of tis- sues (aggressins). & Strategies to overcome nonspecific defenses, especially antiphagocytic mechanisms (impedins). & Strategies to overcome specific immunity, the most important of which is production of IgA proteases (impedins), molecular mimicry, and immunogen variability. Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  8 1 General Aspects of Medical Microbiology & Damage to host tissues due to direct bacterial cytotoxicity, exotoxins, and 1 exoenzymes (aggressins). & Damage due to inflammatory reactions in the macroorganism: activation of complement and phagocytosis; induction of cytokine production (modu- lins). The above bacterial pathogenicity factors are confronted by the following host defense mechanisms: & Nonspecific defenses including mechanical, humoral, and cellular sys- tems. Phagocytosis is the most important process in this context. & Specific immune responses based on antibodies and specific reactions of T lymphocytes (see chapter on immunology). The response of these defenses to infection thus involves the correlation of a number of different mechanisms. Defective defenses make it easier for an infection to take hold. Primary, innate defects are rare, whereas acquired, sec- ondary immune defects occur frequently, paving the way for infections by microorganisms known as “facultative pathogens” (opportunists). & Basic Terminology of Infectiology Tables 1.3 and 1.4 list the most important infectiological terms together with brief explanations. The terms pathogenicity and virulence are not clearly defined in their relevance to microorganisms. They are sometimes even used synonymously. It has been proposed that pathogenicity be used to characterize a particular species and that virulence be used to describe the sum of the disease-causing properties of a population (strain) of a pathogenic species (Fig. 1.1) Pathogenicity and virulence in the microorganism correspond to suscept- ibility in a host species and disposition in a specific host organism, whereby an individual may be anywhere from highly disposed to resistant. Determinants of Bacterial Pathogenicity and Virulence Relatively little is known about the factors determining the pathogenicity and virulence of microorganisms, and most of what we do know concerns the disease-causing mechanisms of bacteria. Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license.  Host–Pathogen Interactions 9 Table 1.3 Basic Infectiological Terminology I (Pathogen) 1 Term Explanation Saprophytes These microorganisms are nonpathogenic; their natural habitat is dead organic matter Parasites Unicellular or metazoan organism living in or on an organism of another species (host) on the ex- pense of the host – Commensals Normal inhabitants of skin and mucosa; the nor- mal flora is thus the total commensal population (see Table 1.7, p. 25) – Pathogenic microorganisms Classic disease-causing pathogens – Opportunists or Can cause disease in immunocompromised indi- facultatively viduals given an “opportune” situation; these are pathogenic frequently germs of the normal flora or occa- microorganisms sionally from the surrounding environment, ani- mals, or other germ carriers Pathogenicity Capacity of a pathogen species to cause disease Virulence Sum of the disease-causing properties of a strain of a pathogenic species Incubation period Time between infection and manifestation of disease symptoms; this specific disease charac- teristic can be measured in hours, days, weeks, or even years Prepatency A parasitological term: time between infection and first appearance of products of sexual re- production of the pathogen (e.g., worm eggs in stool of a host