Molecular Paradigms of Infectious Disease

by Nickerson, Cheryl A.; Schurr, Michael J.

• ISBN13: 9780387309170
• ISBN10: 0387309179
• Edition: 1st
• Format: Hardcover
• Copyright: 2006-07-14
• Publisher: Springer Verlag

Summary

This volume provides an overview of host genetic factors that provide complete or partial resistance to infection, that influence the clinical outcome of infection, or that give the capacity to remain healthy during infection. Progress in the molecular analysis of genetic susceptibility to human and animal infectious diseases has been very rapid over the last few years. Several genes involved in resistance to HIV/AIDS, tuberculosis, malaria, viral hepatitis, herpesvirus infections, and several others have now been identified, and their functions have party or completely been elucidated. This book covers the most recent advances in the field and explores how progress in knowing the genetic basis of infectious diseases could lead to new insights in understanding and combating them.

Table of Contents

Preface	vii
Contributors	ix
Chapter 1: Genetic Analysis of Bacterial Pathogenesis	1	(33)
James M. Slauch
1. Introduction	2	(1)
2. Fusion-based Techniques for Identification of Virulence Genes	3	(11)
2.1. TnPhoA	3	(2)
2.2. In vivo Expression Technology	5	(8)
2.3. Variations on the IVET Theme	13	(1)
3. Transposon-based Techniques for Identification of Virulence Genes	14	(8)
3.1. Signature-tagged Mutagenesis	16	(1)
3.2. Genomic Analysis and Mapping by in vitro Transposition	17	(2)
3.3. Transposon Site Hybridization	19	(3)
4. Classic Bacterial Genetics in an Animal Model	22	(3)
5. Conclusions	25	(9)
Chapter 2: Genetic Exchange in Bacteria and the Modular Structure of Mobile DNA Elements	34	(44)
James W. Wilson
1. Introduction	36	(4)
1.1. Vehicles that Mediate Horizontal Gene Transfer	38	(1)
1.2. The Four Major Horizontal Transfer Paradigms: Transformation, Conjugation, Transduction, and Transposition	39	(1)
2. Transformation Mechanisms	40	(5)
2.1. Gram-positive Transformation	40	(2)
2.2. Gram-negative Transformation	42	(1)
2.3. The Helicobacter pylori DNA Uptake Mechanism Is Related to Type IV Secretion	42	(2)
2.4. Competence Induction	44	(1)
3. Plasmid Replication, Conjugation, and Maintenance	45	(10)
3.1. Plasmid Replication	45	(4)
3.2. Plasmid Conjugation	49	(4)
3.3. Plasmid Maintenance Functions	53	(2)
3.4. Example of a Virulence Plasmid from Yersinia pestis	55	(1)
4. Bacteriophages and Transduction	55	(6)
4.1. Lytic and Lysogenic Bacteriophages	55	(3)
4.2. Generalized and Specialized Transduction	58	(1)
4.3. Regulation of Phage-encoded Toxins by Host-encoded Regulators: Diphtheria Toxin and Cholera Toxin	59	(2)
5. Transposons and the Transposition of DNA	61	(4)
5.1. Insertion Sequences, Composite Transposons, and Noncomposite Transposons	62	(2)
5.2. Cut-and-paste Versus Replicative Transposition	64	(1)
6. The Modular Structure of Mobile Genetic Elements	65	(8)
6.1. Genetic Modules Found in Mobile DNA Elements	65	(2)
6.2. Other Types of Mobile Genetic Elements that Are Combinations of Modules	67	(6)
7. Conclusions A World of Genetic Modules	73	(5)
Chapter 3: Genomics and the Use of Genomic Tools to Study Pathogenic Bacteria	78	(37)
Barry S. Goldman and Conrad Hailing
1. Introduction	80	(1)
2. Genome Sequencing and Assembly	81	(4)
2.1. Required Resources	81	(1)
2.2. Whole Genome Shotgun Sequencing	82	(1)
2.3. Creating a Shotgun Library	82	(2)
2.4. Generating Sequence Reads	84	(1)
2.5. Assembling the Sequence of the Genome	84	(1)
3. Genome Annotation	85	(5)
3.1. Identification of Open Reading Frames	85	(1)
3.2. Identification of Other Elements	86	(1)
3.3. Protein Domain-based Annotation	86	(1)
3.4. Metabolic Pathway-based Annotation	87	(1)
3.5. Annotation Error	87	(2)
3.6. Problems in Annotation Methodology	89	(1)
3.7. Removing Annotation Errors	89	(1)
4. Microarray Technologies	90	(5)
4.1. Transcriptional Profiling Methodologies	90	(2)
4.2. Sources of Variability.	92	(1)
4.3. Statistical Analysis of Microarray Data	93	(1)
4.4. Microarray-based Findings	93	(1)
4.5. Identifying Genomic 'Variation using DNA Microarrays	94	(1)
4.6. Problems with Microarray Technology	95	(1)
5. Comparative Genomics	95	(4)
5.1. Pre-genomics Taxonomy	95	(1)
5.2. 16S rRNA-based Taxonomy	96	(1)
5.3. Horizontal Gene Transfer	96	(1)
5.4. Methods for Detecting Horizontal Transfer	97	(2)
6. Themes of Pathogenicity Determined from Genomic Analysis	99	(2)
6.1. Evolution Driven by Horizontal Gene Transfer	99	(1)
6.2. Pathogenicity Islands	100	(1)
6.3. Plasmids as Mobile Pathogenicity Islands	100	(1)
6.4. Hypervariable Regions	100	(1)
6.5. Reduced Horizontal Transfer in Intracellular Pathogens	101	(1)
7. Genomic Rearrangements Syntenic Maps Give a View of Vertical Descent	101	(3)
8. Conclusions	104	(12)
8.1. Genomic Space	104	(11)
Chapter 4: Pathogenicity Islands and Bacterial Virulence	115	(23)
Michael Hensel
1. Introduction	116	(1)
2. How Did Bacteria Learn to Infect and Colonize Host Organisms?	116	(1)
2.1. Horizontal Gene Transfer	117	(1)
3. Features of Pathogenicity Islands	117	(6)
3.1. Pathogenicity Islands form Insertions in the Genome of Bacteria	118	(1)
3.2. Virulence Genes in Pathogenicity Islands	118	(3)
3.3. Base Composition of Pathogenicity Islands	121	(1)
3.4. Genetic Instability of Pathogenicity Islands	122	(1)
3.5. Pathogenicity Islands and Genes for tRNAs	123	(1)
4. Identification of New Pathogenicity Islands	123	(1)
5. Evolution and Transfer of Pathogenicity Islands	124	(2)
5.1. Transformation and Pathogenicity Islands	124	(1)
5.2. Bacteriophages and Pathogenicity Islands	125	(1)
5.3. Pathogenicity Islands and Virulence Plasmids	125	(1)
6. Paradigms of Pathogenicity Islands and Their Role in Bacterial Pathogenesis	126	(6)
6.1. Pathogenicity Islands of Pathogenic Escherichia coil	127	(1)
6.2. The cag Pathogenicity Islands of Helicobacter pylori	127	(1)
6.3. The High Pathogenicity Island of Yersinia spp	128	(1)
6.4. Pathogenicity Islands in Salmonella spp	128	(1)
6.5. Pathogenicity Islands in Staphylococcus aureus	129	(3)
7. Specific Aspects of Pathogenicity Islands	132	(2)
7.1. Mosaic Pathogenicity Islands	132	(1)
7.2. Regulation of Virulence Genes in Pathogenicity Islands	132	(1)
7.3. Black Holes: Virulence Due to the Lack of Genes?	132	(1)
7.4. Do all Pathogens Possess Pathogenicity Islands?	133	(1)
7.5. Genomic Islands in Nonpathogenic Bacteria and 'Fitness Islands'	133	(1)
8. Conclusions	134	(4)
Chapter 5: Capsules	138	(38)
Robert T. Cartee and Janet Yother
1. Introduction	139	(1)
2. Roles of Capsules in Pathogenesis	140	(5)
2.1. Interference with Complement-mediated Effects	142	(1)
2.2. Adherence and Colonization	143	(1)
2.3. Other Functions	144	(1)
2.4. Protective Immune Responses	144	(1)
3. Genetics and Classification of Capsules	145	(5)
3.1. Surface Polysaccharides of E. coli	146	(1)
3.2. Group 1 Capsules of E. coli	146	(2)
3.3. Groups 2 and 3 Capsules of E coli	148	(1)
3.4. Group 4 Capsules of E. coli	149	(1)
3.5. Capsules of Gram-positive Bacteria	150	(1)
4. Mechanisms of Capsule Synthesis	150	(14)
4.1. Block-type, or Wzy-dependent, Pathway	152	(6)
4.2. ABC-2 Transporter-dependent Pathway	158	(3)
4.3. Synthase-dependent Pathway	161	(3)
5. Nonpolysaccharide Capsules	164	(1)
6. Conclusions	165	(11)
Chapter 6: Bacterial Cell Walls	176	(31)
Jennifer K. Wolf and Joanna B. Goldberg
1. Introduction	177	(1)
2. The Gram Stain	177	(2)
3. Grant-positive Bacteria	179	(3)
4. Gram-negative Bacteria	182	(6)
5. Notable Exceptions	188	(1)
5.1. Acid-fast Bacteria	188	(1)
5.2. Mycoplasmas	189	(1)
6. Cytoplasmic Membrane Components	189	(1)
7. Externally Exposed Structures	190	(7)
7.1. Flagella	191	(1)
7.2. Pili	192	(2)
7.3. Type III Secretion Apparatus	194	(1)
7.4. Porins	195	(1)
7.5. Outer Membrane Transporters	196	(1)
7.6. Efflux Pumps	196	(1)
8. Cell Wall Antibiotics	197	(1)
8.1. Antibiotics Affecting Early Steps in Peptidoglycan Synthesis	197	(1)
8.2. β-Lactarn Antibiotics	198	(1)
8.3. Isoniazid	198	(1)
9. Antibiotic Resistance	198	(2)
10. Innate Immune Response to Cell Wall Components	200	(1)
11. Conclusions	201	(6)
Chapter 7: Mechanisms of Bacterial Adhesion and Consequences of Attachment	207	(40)
Gregory G. Anderson, Yvonne M. Lee, Craig L. Smith, and Scott J. Hultgren
1 Introduction	208	(1)
2. Diversity of Adhesins	209	(17)
2.1. The Chaperone/Usher Pathway of Adhesin Assembly	209	(6)
2.2. Type IV Pili	215	(3)
2.3. Afimbrial Adhesive Structures	218	(4)
2.4. Gram-positive Adhesins	222	(3)
2.5. Other Adhesins	225	(1)
3. Consequences of Adhesion	226	(9)
3.1. Activation of Bacterial Signaling Pathways	226	(1)
3.2. Colonization of the Host	227	(1)
3.3. Biofilm Formation	228	(1)
3.4. Bacterial Invasion of Host Tissues	229	(3)
3.5. Uropathogenic Escherichia coil Pathogenesis	232	(3)
4. Adhesin-based Technology	235	(2)
4.1. Vaccine Strategies	236	(1)
4.2. Receptor Analogues	237	(1)
5. Conclusions	237	(10)
Chapter 8: Bacterial Invasion into Non-Phagocytic Cells	247	(27)
Daoguo Zhou
1. Introduction	248	(3)
2. Salmonella Invasion	251	(8)
2.1. Pathogenicity Islands and Type III Protein Secretion Systems	251	(2)
2.2. Actin Cytoskeleton Rearrangements and Salmonella Entry into Host Cells	253	(3)
2.3. Role of Salmonella Actin-modulating Proteins in Invasion	256	(2)
2.4. Salmonella-induced Host Cell Signaling	258	(1)
3. Listeria monocytogenes Invasion	259	(5)
3.1. The Internalin Gene Family	259	(2)
3.2. Host Factors Involved in L. monocytogenes Entry	261	(3)
4. Conclusions	264	(10)
Chapter 9: Bacterial Protein Secretion Mechanisms	274	(47)
James W. Wilson
1. Introduction	275	(1)
1.1. Protein Secretion Mechanisms Are Essential for the Interaction of Bacteria with Host Cells	275	(1)
1.2. There Are Sec-dependent and Sec-independent Secretion Pathways	276	(1)
2. The Sec System (The General Secretory Pathway)	276	(7)
2.1. The Gram-negative Sec System	278	(5)
2.2. The Gram-positive Sec System	283	(1)
3. Sec-dependent Secretion Systems	283	(9)
3.1. Type V Secretion: Autotransporters	284	(1)
3.2. Two-partner Secretion (TPS) Pathway	285	(1)
3.3. Chaperone/Usher Pathway	285	(4)
3.4. Type 11 Secretion Pathway	289	(3)
4. Sec-independent Secretion Systems	292	(14)
4.1. Type I Secretion: ABC Transporters	292	(2)
4.2. Type III Secretion Systems	294	(9)
4.3. The Twin-Arginine (TAT) Pathway	303	(3)
5. A Dual Sec-dependent and Sec-independent Secretion System: Type IV Secretion	306	(5)
5.1. Type IV Secretion Systems Are Related to DNA Conjugation Systems and Mediate the Transport of DNA and Proteins	306	(1)
5.2. The Type IV Secretion Apparatus Is a Multiprotein Complex that Spans the Bacterial Cell Envelope	307	(4)
6. Conclusions: Examples of Protein Secretion Systems in Different Pathogens	311	(10)
Chapter 10: Toxins as Host Cell Modulators	321	(83)
Dan Ye and Steven R. Blanke
1. Introduction	323	(1)
2. The Importance of Toxins in Bacterial Pathogenesis	324	(1)
3. What do Toxins Do? An Overview of Toxins at the Cellular and Molecular Level	324	(12)
3.1. An Overview of Toxin Classes and Names	326	(1)
3.2. An Overview of Cellular Intoxication Mechanisms	327	(2)
3.3. An Overview of Eukaryotic Targets	329	(2)
3.4. An Overview of Toxin Structure and Function	331	(5)
4. Genomic Considerations	336	(3)
4.1. The Organization and Nature of Toxin Genes	336	(2)
4.2. Where Do Bacterial Toxins Come From	338	(1)
5. Timing and Location is Everything: Bacteria Regulate When and Where Toxins are Produced	339	(4)
5.1. Two-Component Regulatory Systems of Toxin Production	340	(1)
5.2. Regulation of Toxin Production by Environmental Iron	341	(1)
5.3. Regulatory Systems Shared by Virulence and Nonvirulence Genes	341	(1)
5.4. Quorum Sensing	342	(1)
5.5. Posttranslational Regulation of Toxin Activity	343	(1)
6. Delivering the Goods: Exporting Toxins Out of Bacterial Cells	343	(6)
6.1. Export of Toxins into the Extracellular Host Environment	345	(3)
6.2. Direct Export of Toxins into the Host Cell Cytosol	348	(1)
6.3. Toxins Secretion from Gram-positive Bacteria	349	(1)
7. Toxin Interactions with Host Target Cells	349	(14)
7.1. Host Cell Receptors Mediate Toxin Interactions with Target Cells	350	(5)
7.2. Portals and Pathways: Entry of Intracellular-acting Toxins into Cells	355	(3)
7.3. Portals for Toxin Entry into the Cytosol	358	(3)
7.4. Some Bacterial Toxins Cross Mucosal Barriers by the Process of Transcytosis	361	(1)
7.5. Gram-positive Large Pore-forming Toxins: A Novel Mechanism for the Delivery of Virulence Factors into the Cytosol of Target Cells?	362	(1)
8. Modulation of Target Cell Function	363	(23)
8.1. Extracellular-acting Toxins	364	(7)
8.2. Intracellular-acting Toxins	371	(15)
9. How do Bacterial Toxins Contribute to the Virulence of Pathogenic Bacteria	386	(143)
9.1. Toxins that Facilitate the Acquisition of Nutrients for Bacterial Colonization	386	(1)
9.2. Toxins that Facilitate Bacterial Infection and Dissemination by Remodeling of Host Colonization Niches	387	(1)
9.3. Toxins that Facilitate Colonization and Persistence Through Modulation of the Immune Response	388	(1)
9.4. Toxins that Facilitate Intracellular Lifestyles	388	(1)
10. The Beneficial Manipulation of Toxins as Molecular Tools in Medicine and Basic Science	389	(2)
10.1. The Use of Toxins as Vaccine Adjuvants	389	(1)
10.2. The Use of Toxins as Magic Bullets	389	(1)
10.3. The Use of Toxins as Delivery Vectors	390	(1)
10.4. Toxins as Molecular Reagents in Cell Biology and Pharmacology	391	(1)
11. Novel Countermeasures Against the Insidious Uses of Toxins and Toxin-producing Microbes for Biological Warfare	391	(1)
12. Conclusions	392	(12)
Chapter 11: Quorum Sensing: Coordinating Group Behavior Through Intercellular Signals	404	(34)
Joshua D. Shrout and Matthew R. Parsek
1. Introduction	406	(1)
1.1. Quorum Sensing (QS) is a form of Cell-to-cell Communication that Coordinates Gene Expression Among Groups of Cells	406	(1)
1.2. QS Involves Production of an Extracellular Signal that Affects a Concentration-dependent Response	406	(1)
2. Acyl-Homoserine Lactone (AHL) QS in Gram-negative Bacterial Species	406	(8)
2.1. A Common Type of Gram-negative QS Involves AHL Signal Molecules	406	(1)
2.2. LuxI family members are AHL Synthases	407	(2)
2.3. LuxR family members are AHL Signal Receptors	409	(1)
2.4. The Basic Molecular Scheme for AHL-mediated QS	410	(1)
2.5. QS as a Global Regulatory System	410	(1)
2.6. AHL QS Controls Virulence Functions for Many Pathogens	411	(3)
3. Non-AHL QS Systems in Gram-negative Species	414	(2)
3.1. The Plant Pathogen Ralslonia solanacearuni Utilizes a Volatile Signaling Molecule to Regulate Virulence	414	(1)
3.2. Myxococcus xanthus and Other Myxococcus species Use QS to Form Fruiting Bodies	415	(1)
4. Peptide-based QS in Gram-positive Bacterial Species	416	(6)
4.1. Many Gram-positive QS Systems Use Peptide Signals	416	(2)
4.2. Signal Peptide Structures are Highly Variable	418	(2)
4.3. Some Signal Peptides also Function as Bacteriocins	420	(1)
4.4. QS Controls Competence in Streptococcus pneumoniae	420	(1)
4.5. Staphylococcus aureus Virulence is Controlled by QS	421	(1)
5. Nonpeptide-based QS Systems in Gram-positive species	422	(1)
5.1. The A-factor of Streptomyces species is a γ-Butyrolactone Signal	422	(1)
6. AI-2 QS	423	(4)
6.1. One Form of Interspecies QS Utilizes a Signal Called AI-2	423	(1)
6.2. AI-2 is a Furanosyl Borate Diester that Binds with Two Proteins to Initiate a Signaling Cascade	423	(3)
6.3. AI-2-dependent QS Regulates Virulence Factors in many Species	426	(1)
7. Conclusions	427	(12)
7.1. QS Coordinates Gene Expression through Extracellular Signaling Molecules	427	(1)
7.2. Many Gram-negative Species Utilize AHL Signaling Molecules	427	(1)
7.3. QS in Gram-positive Species Commonly Uses Peptide Signals	427	(1)
7.4. QS Controls Virulence functions in many Bacterial Species	427	(11)
Chapter 12: The Role of Sigma Factors in Regulating Bacterial Stress Responses and Pathogenesis	438	(64)
Clint Coleman, Chasity Baker, and Cheryl A. Nickerson
1. Introduction	439	(10)
1.1. Bacterial Stress Responses and Sigma Factors	439	(2)
1.2. Bacteria Use Sigma Factors to Activate Transcription of Genes	441	(3)
1.3. Alternative Sigma Factors Activate Expression of Specialized Gene Sets in Response to Environmental Stimuli	444	(5)
2. Bacteria Use Alternative Sigma Factors to Regulate the Expression of Virulence Genes	449	(30)
2.1. Sigma 38 The Major Stress Response Regulator	449	(8)
2.2. Sigma B The General Stress Response Regulator in Gram-positive Bacteria	457	(5)
2.3. Sigma 32 Heat Shock	462	(6)
2.4. Sigma 24 Periplasmic Stress	468	(4)
2.5. Sigma 28 Motility and Chcmotaxis Genes	472	(4)
2.6. In a Class by Itself: σ54- Nitrogen Metabolism and So Much More!	476	(3)
3. Conclusions	479	(1)
4. Questions to Consider	480	(22)
Chapter 13: Two-Component Regulatory Systems	502	(42)
Lisa A. Morici, Anders Frisk, and Michael J. Schurr
1. Introduction	503	(2)
2. Structure, Function, and Classification of Histidine Kinases	505	(3)
2.1. Sensing Domains of Histidine Kinases	506	(1)
2.2. Linker Domains of Histidine Kinases	507	(1)
2.3. Histidine Phosphotransfer Domains of Histidine Kinases	507	(1)
2.4. Kinase Catalytic Core of Histidine Kinases	508	(1)
3. Structure and Function of Response Regulators	508	(4)
3.1. Phosphoryl-Aspartate Receiver Domains	510	(1)
3.2. Output Domains of Response Regulators	510	(2)
4. Role of the Two-Component Regulators in Pathogenesis	512	(17)
4.1. The Gram-negative Two-Component Regulatory System PhoPQ	512	(11)
4.2. BvgAS, a Two-Component Regulatory System in Borcletelki pertussis	523	(6)
5. Conclusions	529	(15)
Chapter 14: Oxidative Stress Systems in Bacteria: Four Model Organisms	544	(31)
Daniel J. Hassett and James A. Imlay
1. Introduction	547	(1)
2. Oxygen Toxicity and Reactive Oxygen Species	547	(2)
3. How Do O2- and H2O2 Arise Inside Escherichia coli?	549	(2)
4. How Does O2- Injure Cells?	551	(1)
5. How Does H2O2 Injure Cells?	552	(1)
6. Inducible Cell Defenses Against O2- and H2O2	553	(1)
7. Oxidative Stress in the Escherichia coli Periplasmic Space	554	(1)
8. Pseudomonas aeruginosa: An Obligate Respirer	554	(1)
9. Oxidative Stress Systems in Pseudomonas aeruginosa	555	(1)
10. SOD	555	(2)
10.1. Fe-SOD	555	(1)
10.2. Mn-SOD	556	(1)
11. Catalase	557	(4)
11.1. KatA	557	(1)
11.2. KatB and AnkB	558	(1)
11.3. KatC	559	(2)
12. Alkyl Hydroperoxide Reductase	561	(1)
13. OxyR	561	(2)
14. Glucose-6-Phosphate Dehydrogenase	563	(1)
15. The Phagocytic Respiratory Burst: Two Important Pathogens that Resist Killing	563	(1)
15.1. Salmonella ophimurium Oxidative Stress Systems	563	(1)
16. Mycobacterium tuberculosis Oxidative Stress Systems	564	(1)
17. Conclusions	565	(10)
Chapter 15: Bacterial Biowarfare Agents	575	(44)
Mark Soboleski, Audrey Glynn, and Lucy Cardenas-Freytag
1. Biowarfare Agents and Historical Perspective	576	(1)
2. Anthrax	577	(12)
2.1. Introduction	577	(1)
2.2. Pathogenesis	578	(3)
2.3. Virulence	581	(5)
2.4. Treatment and Prevention	586	(1)
2.5. Vaccines and Immunity	587	(2)
3. Plague	589	(9)
3.1. Introduction	589	(1)
3.2. Pathogenesis	590	(2)
3.3. Virulence	592	(3)
3.4. Treatment	595	(1)
3.5. Vaccines and Immunity	595	(3)
4. Tularemia	598	(21)
4.1. Introduction	598	(1)
4.2. Pathogenesis	599	(1)
4.3. Virulence	599	(2)
4.4. Vaccines and Immunity	601	(18)
Index	619