E-raamat: Pathogenomics: Genome Analysis of Pathogenic Microbes [Wiley Online]

Foreword		v
Preface		xix
List of Contributors		xxi
Color Plates		xxvii
I. Methods		1	(82)
Bioinformatics: Data Mining Among Genome Sequences		3	(18)
Susanne Kneitz
Thomas Dandekar
Systematic Genome Analysis of Pathogens as a Basis for Pharmacogenomic Strategies		3	(1)
Direct Sequence Annotation Tools for Functional Genomics		4	(1)
Identification of Protein Function		4	(1)
Obtaining Protein Information from a Domain Server		5	(1)
Pathway Analysis		6	(1)
Network Analysis		7	(1)
Adaptation in Time and to Stimuli		8	(5)
Experimental Design for Microarray Analysis		8	(1)
Data Analysis		9	(4)
Pathogen-Specific Challenges		13	(1)
Pathogen Adaptation Potential		14	(1)
The Fight Against Resistance		14	(1)
Drug Design and Antibiotics		15	(1)
Annotation Platforms Suitable for Pathogenomics		15	(2)
Conclusions		17	(4)
Transcriptome Analysis: Towards a Comprehensive Understanding of Global Transcription Activity		21	(22)
Ben Sidders
Neil Stoker
Introduction		21	(1)
Development of Transcriptomics		21	(2)
From Genomics to Functional Genomics		21	(1)
From Gene to Whole Genome		22	(1)
Introducing the Microarray		23	(2)
What Is a Microarray?		23	(1)
The Affymetrix Gene Chip		23	(1)
The Spotted Microarray		24	(1)
Microarray Methods		25	(7)
Experimental Design		25	(1)
Type of Experiment		25	(3)
Replicates		28	(1)
RNA Extraction		28	(2)
Labeling/Reverse Transcription		30	(1)
Hybridization		31	(1)
Scanning		31	(1)
Data Normalization and Analysis		32	(5)
Image Quantification		32	(1)
Data Processing		33	(1)
Data Analysis		34	(1)
Detection of Differential Expression		34	(1)
Pattern Recognition		35	(1)
Graphical Representations		35	(1)
Microarray Analysis Tools		36	(1)
Microarray Follow-Up		36	(1)
Data Storage and Reanalysis		37	(1)
Transcriptomics: Where We Are Now and What's to Come		37	(6)
Physiological Proteomics of Bacillus subtilis and Staphylococcus aureus: Towards a Comprehensive Understanding of Cell Physiology and Pathogenicity		43	(26)
Michael Hecker
Susanne Engelmann
Introduction		43	(3)
Proteomics of Bacillus subtilis: The Gram-positive Model Organism		46	(7)
The Vegetative Proteome		46	(1)
Proteomes of Nongrowing Cells: Proteomic Signatures of Stress/Starvation Stimuli		47	(6)
Physiological Proteomics of Staphylococcus aureus		53	(12)
The Postgenome Era of S. aureus		53	(3)
Proteomes of Growing and Nongrowing Cells		56	(6)
Extracellular Proteins and Pathogenicity Networks		62	(3)
Outlook: Second Generation Proteomics and New Fields in S. aureus Physiology and Infection Biology		65	(4)
Impact of Genome Sequences on Mutational Analysis of Fungal and Bacterial Pathogens		69	(14)
Vladimir Pelicic
Xavier Nassif
The Long Road from Sequence to Function		69	(1)
Classical Genetics Still at the Forefront in the Postgenome Era		70	(2)
Reverse Genetics		70	(1)
Transposon Mutagenesis		71	(1)
Genome-Scale Mutational Analyses		72	(7)
Saccharomyces cerevisiae		73	(2)
Bacterial Workhorses: E. coli and Bacillus subtilis		75	(1)
Bacterial Pathogens		75	(1)
Mycoplasma Species		76	(1)
Pseudomonas aeruginosa		76	(1)
Staphylococcus aureus		77	(1)
Neisseria meningitidis		77	(2)
Conclusion		79	(4)
II. Genomics of Pathogenic Bacteria		83	(284)
Pathogenomics of Escherichia coli and Shigella Species		85	(24)
Ulrich Dobrindt
Jorg Hacker
Introduction		85	(1)
Comparative Genomics of Shigella		86	(6)
Comparative Genomics of Escherichia coli		92	(9)
Comparison of Complete Genome Sequences		92	(2)
Comparative Genomics Using DNA Arrays		94	(1)
Mobile Genetic Elements and Evolution of Pathogenic E. coli		95	(1)
Genomic Islands/Pathogenicity Islands		95	(4)
Plasmids and Bacteriophages		99	(1)
Genetic Diversity Among Extraintestinal Pathogenic E. coli		100	(1)
Conclusions		101	(8)
Pathogenomics of Salmonella Species		109	(16)
Helene Andrews-Polymenis
Andreas J. Baumler
Introduction		109	(1)
Salmonella Signature Genes		109	(3)
Subspecies I Signature Genes		112	(3)
Host Restriction		115	(10)
Pathogenomics of Enterococcus faecalis		125	(24)
Janet M. Manson
Michael S. Gilmore
Introduction		125	(1)
Enterococcal Pathogenesis		125	(1)
Genome Sequence of E. faecalis		126	(14)
Mobile Elements, Acquired DNA, and Antimicrobial Resistance		127	(4)
Environmental Adaptation and Stress Response		131	(2)
Survival In Vivo		133	(1)
Potential Virulence Factors		134	(1)
Hemolysins, Proteases, and other Enzymes		134	(2)
Cell-Wall-Associated Virulence Factors		136	(2)
Pathogenicity Island of E. faecalis		138	(2)
Conclusions and Future Perspectives		140	(9)
Genomics of Streptococci		149	(26)
Joseph J. Ferretti
W. Michael McShan
Introduction		149	(3)
Bacterial Genomes		152	(10)
Pyogenic Group		152	(1)
Streptococcus pyogenes		152	(1)
Virulence Factors		153	(1)
Horizontal Gene Transfer		154	(1)
Streptococcus agalactiae		155	(1)
Group C (GCS) and Group G Streptococci		156	(1)
Streptococcus uberis		157	(1)
Bovis Group		157	(1)
Streptococcus bovis and Streptococcus suis		157	(1)
Mitis Group		158	(1)
Streptococcus pneumoniae		158	(1)
Streptococcus mitis, Streptococcus sanguis, and Streptococcus gordonii		159	(1)
Anginosus and Salivarius Group		159	(1)
Streptococcus salivarius		159	(1)
Streptococcus thermophilus		160	(1)
Mutans Group		160	(1)
Streptococcus mutans and Streptococcus sobrinus		160	(1)
Other Organisms: Enterococcus faecalis		161	(1)
Comparative Genomics		161	(1)
Streptococcal Genomic Bacteriophages		162	(13)
Prophages and Streptococcal Genomes		162	(1)
GAS Genome Prophages		163	(1)
Prophages and Virulence Factors		163	(2)
Prophage Attachment Sites and Host Biology		165	(1)
Prophage Diversity		166	(1)
Prophages Associated with other Streptococcal Species		166	(9)
Pathogenic Staphylococci: Lessons from Comparative Genomics		175	(36)
Knut Ohlsen
Martin Eckart
Christian Huttinger
Wilma Ziebuhr
Introduction		175	(1)
Comparative Genomics of S. aureus		176	(19)
Overall Genome Structure		177	(1)
Core Genome		178	(1)
Metabolism		178	(2)
Information Pathways		180	(1)
Virulence Factors		181	(3)
Accessory Genome		184	(1)
Pathogenicity Islands		185	(5)
Staphylococcal Cassette Chromosome		190	(2)
Bacteriophages		192	(2)
Plasmids		194	(1)
Staphylococcus epidermidis		195	(7)
Genomic Islands		197	(1)
Phage SPβ and other Bacillus Genes		197	(1)
Virulence Factors		197	(1)
Staphylococcal Cassette Chromosome		198	(1)
Adherence and Biofilm Formation		199	(2)
Insertion Sequences		201	(1)
Concluding Remarks		202	(9)
Pathogenomics: Insights into Tuberculosis and Related Mycobacterial Diseases		211	(20)
Alexander S. Pym
Stephen V. Gordon
Roland Brosch
Introduction		211	(1)
Molecular Basis of Pathogenicity		212	(4)
Evolution of the M. tuberculosis Complex		216	(4)
Some Metabolic Insight from the Genome Sequences		220	(2)
Other Major Mycobacterial Human Pathogens		222	(2)
Mycobacterium leprae		222	(1)
Mycobacterium ulcerans		223	(1)
Concluding Remarks		224	(7)
Genomes of Pathogenic Neisseria Species		231	(26)
Christoph Schoen
Heike Claus
Ulrich Vogel
Matthias Frosch
Introduction		231	(1)
Genomes of Pathogenic Neisseria Species		232	(17)
The Flexible Genome Pool		233	(3)
Repetitive DNA Sequence Elements Govern Neisserial Biology		236	(1)
DNA Uptake Sequences, Horizontal Gene Transfer, and Antigenic Diversity		236	(1)
Simple Sequence Repeats and Phase Variation		237	(1)
Insertion Sequences and the Regulation of Gene Expression		238	(1)
Genome-Wide Mutational Analyses		239	(1)
Comparative Genomics		240	(4)
Novel Virulence Factors of Meningococci Identified by Genomic Approaches		244	(5)
Future Perspectives		249	(8)
Genomics of Pathogenic Clostridia and Bacilli		257	(24)
Armin Ehrenreich
Gerhard Gottschalk
Holger Bruggemann
Genomics of Pathogenic Clostridia spp.		257	(8)
Introduction		257	(1)
C. perfringens		258	(2)
C. tetani		260	(2)
C. botulinum		262	(1)
C. difficile		263	(1)
Conclusions and Perspectives		264	(1)
Genomics of Pathogenic Bacilli		265	(16)
Introduction		265	(1)
Pathogenic Properties of Bacilli not Belonging to the B. cereus Group		266	(1)
Pathogenicity of B. cereus		266	(2)
Pathogenicity of B. anthracis		268	(1)
Course of Anthrax		268	(1)
Virulence Factors of B. anthracis		269	(1)
Genome of B. anthracis		270	(1)
Chromosomal Genes		270	(1)
Genes Located on Plasmids pXO1 and pXO2		271	(1)
Regulation of Virulence Genes		272	(1)
Molecular Diversity in B. anthracis Genomes		272	(1)
Genome of a Highly Virulent B. cereus Strain Resembling B. anthracis in Pathogenesis		273	(1)
Comparison of B. cereus Group Genomes: How Did Pathogenicity Evolve?		273	(8)
The Genomes of Pathogenic Bartonella Species		281	(20)
Carolin Frank
Eva Berglund
Siv G. E. Andersson
Introduction		281	(3)
Bartonella in a Phylogenetic Context		281	(1)
Hosts and Vectors for Bartonella Species		282	(2)
Bartonella Species and Pathogenicity		284	(2)
Infection of Reservoir and Incidental Host		284	(1)
Bartonella Species as Human Pathogens		285	(1)
The Bartonella Genomes		286	(1)
Genomic Islands and Phages		286	(1)
Genomic Islands and Phages in Bartonella Species		287	(4)
The B. henselae Prophage		288	(1)
B. henselae Genomic Islands and Islets		288	(2)
B. quintana Harbors Remnants of the B. henselae Islands		290	(1)
Role of Phages and Islands in the Evolution of Bartonella		290	(1)
The Chromosome II-Like Segment in Bartonella		291	(3)
Type IV Secretion Systems in Bartonella Species		292	(1)
The vir B-D4 Operon		293	(1)
The trw Operon		293	(1)
B. quintana's Evolution into a Human Pathogen		294	(1)
Conclusions and Future Perspectives		295	(6)
Pathogenomics of Gastric and Enterohepatic Helicobacter Species		301	(14)
Sebastian Suerbaum
Sandra Schwarz
Christine Josenhans
Introduction		301	(1)
Helicobacter pylori		302	(3)
Key Features of the H. pylori Genome Related to Pathogenesis		302	(1)
Colonization Factors: Urease and Motility		302	(1)
Phase Variation		302	(1)
The H. pylori Outer Membrane Protein Family		303	(1)
Intraspecies Variation of H. pylori Genomes		303	(1)
The cag Pathogenicity Island		304	(1)
Nucleotide Sequence Variation in H. pylori		305	(1)
Helicobacter hepaticus		305	(2)
The HHGI1 Genomic Island		306	(1)
Other Putative H. hepaticus Virulence Factors		307	(1)
Genome Comparisons of Gastric and Enterohepatic Helicobacter Species with Related Bacteria		307	(1)
Outlook		308	(7)
Genomics of the Opportunistic Pathogen Legionella pneumophila		315	(24)
Christel Cazalet
Carmen Buchrieser
The Genus Legionella: Epidemiology, Life Cycle, and Pathogenesis		315	(1)
Genomics of Legionella pneumophila		316	(2)
Specific Features of the Legionella Genomes		318	(15)
Eukaryotic-like Proteins in Legionella pneumophila: Modulation of Host Functions?		318	(6)
Secretion Machineries of L. pneumophila: Central to Its Life and to Pathogenesis		324	(1)
Type IV Secretion Systems in Legionella		325	(1)
The dot/icm Type IVB Secretion System		325	(1)
The Ivh Type IVA Secretion System		326	(1)
A Putative Type I Secretion System in Legionella		326	(1)
A Type II Secretion System in Legionella		327	(1)
Secretion Across the Cytoplasmic Membrane		327	(1)
A Putative Type V Secretion System (Autotransporter) Specific to Strain Paris		328	(1)
Comparative Genomics: Diversity of the Species L. pneumophila		329	(1)
Genomic (Pathogenicity) Islands in the L. pneumophila Genomes		329	(2)
Plasmids and Genetic Diversity of L. pneumophila		331	(2)
Conclusions		333	(6)
Genomics of Listeria monocytogenes		339	(28)
Michael Kuhn
Werner Coebel
Introduction: From Pregenomics to Postgenomics		339	(1)
Listeria monocytogenes: A Facultative Intracellular Pathogen		339	(1)
Listeria monocytogenes Genetics in the Pregenomic Era: Identification and Characterization of Important Virulence Factors		340	(6)
Internalins and the Invasion of Nonprofessional Phagocytic Cells		340	(2)
Listeriolysin O and Two Listerial Phospholipases Allow Escape from the Phagocytic Vacuole		342	(1)
Intracellular Motility and Cell-to-Cell Spread: The Surface Protein ActA		343	(1)
PrfA and the Regulation of Virulence Gene Expression		344	(2)
Genome Sequence of L. monocytogenes and Its Comparison with the Closely Related L. innocua		346	(2)
Genomic Approaches to Studying the other Members of the Genus Listeria		348	(1)
Evolutionary Aspects		349	(2)
Identification of Listerial Virulence Factors in the Postgenomic Era		351	(4)
Internalins and Other Surface Proteins		351	(1)
Growth in the Host Cell Cytoplasm		352	(1)
Resistance to Bile		353	(1)
Two-component Systems and the Regulation of Virulence Gene Expression		354	(1)
Vitamin B12 Biosynthesis and Anaerobic Use of Ethanolamine		354	(1)
Proteomics		355	(1)
Transcriptomics		356	(2)
Conclusions		358	(9)
III. Genomics of Pathogens and Their Hosts: Applications		367	(188)
Genomics of Viruses		369	(20)
Esteban Domingo
Alejandro Brun
Jose Ignacio Nunez
Juan Cristina
Carlos Briones
Cristina Escarmis
Introduction: Wide Scope of Virogenomics		369	(2)
Retrieving Information		371	(3)
Applications of Data Banks to Virology		374	(5)
Beyond Reference Strains: Towards a Second-Generation Virogenomics?		379	(3)
Virogenomics Through Microarrays		382	(7)
Genomics of Pathogenic Fungi		389	(28)
Gerwald A. Kohler
Alan Kuo
George Newport
Nina Agabian
Introduction		389	(1)
Genomics of Primary Fungal Pathogens		390	(7)
Histoplasma		390	(6)
Coccidioides		396	(1)
Blastomyces and Paracoccidioides		396	(1)
Genomics of Opportunistic Fungal Pathogens		397	(9)
Aspergillus		397	(1)
Cryptococcus		398	(3)
Pneumocystis		401	(1)
Microsporidia		402	(1)
Candida		403	(3)
The Tool Box for Functional Genomics		406	(4)
Expression Analysis		407	(1)
Transformation and Mutagenesis		407	(3)
Fungal Virulence -- From the Genomic Point of View		410	(1)
Conclusion		411	(6)
Genomics of Pathogenic Parasites		417	(28)
Gabriele Pradel
Thomas James Templeton
Exploring the Genomes of Pathogenic Protozoans		418	(2)
The Shaping of the Proteomes of the Pathogenic Protists		420	(1)
Role of Horizontal Gene Transfer in Protozoan Genome Plasticity		421	(1)
The Apicomplexa		422	(7)
Plasmodium, the Malaria Parasite		423	(4)
Cryptosporidium		427	(1)
Toxoplasma		428	(1)
The Pathogenic Kinetoplastids		429	(2)
Trypanosoma		430	(1)
Leishmania		431	(1)
The Pathogenic Diplomanad Giardia and the Parabasalid Trichomonas		431	(2)
Postgenomic Strategies and the Search for Cure		433	(12)
Gene Expression Analysis		434	(1)
Proteomics		434	(1)
Drug and Vaccine Development		435	(1)
Vector Genetics		436	(9)
Model Host Systems: Tools for Comprehensive Analysis of Host-Pathogen Interactions		445	(12)
Michael Steinert
Gernot Glockner
Introduction		445	(1)
Host-Pathogen Interactions		446	(1)
Arabidopsis thaliana: A Plant as a Model for Human Disease		447	(1)
Dictyostelium discoideum: Perspectives from a Social Amoeba		448	(1)
Caenorhabditis elegans: Answers from a Worm		449	(1)
Drosophila melanogaster: A Fruitful Model		450	(1)
Danio rerio: Fishing for Knowledge		451	(1)
Mus musculus: Of Mice and Men		451	(2)
Clean Models and Dirty Reality		453	(4)
Expression Analysis of Human Genes During Infection		457	(24)
Erwin Bohn
Ingo B. Autenrieth
Introduction		457	(1)
Comparison of Gene Expression Profiles of Macrophages and Dendritic Cells In Vitro Upon Infection with Different Pathogens		458	(2)
Septicemia		460	(1)
Gene Expression in Epithelial Cells Modulated by Bacteria		461	(8)
Helicobacter pylori		462	(2)
Yersinia enterocolitica		464	(2)
Pseudomonas aeruginosa		466	(2)
Bartonella henselae		468	(1)
Common Signatures		469	(2)
Genetic Polymorphisms and Mutations Affect Gene Expression: Impact on Infection Susceptibility and Infection Course		471	(2)
Concluding Remarks		473	(8)
Pathogenomics: Application and New Diagnostic Tools		481	(24)
Soren Schubert
Jurgen Heesemann
Introduction: ``In Our Hands''		481	(1)
Microbiological Diagnostics of Bacterial Pathogens: Aims, Tasks, and Current Limitations		482	(1)
The Pregenomic Era: Conventional and Molecular Methods in Microbiological Diagnostics		483	(4)
Conventional Culture-Based Methods in Microbiological Diagnostics		483	(1)
Molecular Microbiological Diagnostic Methods		484	(1)
Typing of Bacterial Isolates Using 16S-rRNA		484	(1)
Fluorescence In Situ Hybridization		484	(1)
PCR Methods for Microbial Diagnostics		485	(2)
The Postgenomic Era: Use of DNA Microarrays in the Diagnosis of Infectious Diseases in Humans and Animals		487	(8)
DNA Arrays: Platforms, Techniques and Targets		487	(1)
Detection and Typing of Microbial Pathogens		488	(1)
Pathoarrays		489	(5)
16S-/23S-rDNA Arrays		494	(1)
Detection of Antibiotic Resistance in Microbial Pathogens Using Microarray Technology		494	(1)
Microarray Technology in Bacteria: Further Areas of Applications		495	(3)
Gene Expression Microarrays and Host-Pathogen Interaction		495	(1)
DNA Microarray Technology in Food Technology		496	(1)
DNA Microarray Technology in Environmental Microbiology		496	(1)
Pathogenomic Tools (Microarrays) in the Diagnosis of Microbiologic Agents as Biovyeapons		497	(1)
Current Limitations on the Use of DNA Microarrays in Diagnostics in Medical Microbiological Laboratories		498	(1)
Final Remarks		498	(7)
The Search for New Antibiotics		505	(28)
Harald Labischinski
Christoph Freiberg
Heike Brotz-Oesterhelt
The Need for Novel Antibiotics		505	(2)
Where Will the New Antibiotics Come From?		507	(6)
The Past		507	(2)
The Present		509	(2)
Future Directions		511	(2)
Contributions of Genomic Technologies to Antibacterial Research		513	(8)
Target Identification and Validation		513	(4)
Target Prioritization		517	(1)
Genetic Tools for Drug Screening and Mode-of-Action Determination		517	(3)
Genome-Wide Expression Profiling for Mode-of-Action Characterization		520	(1)
Outlook for Genomic Technologies for Antibiotic Drug Discovery		521	(1)
Alternative Approaches in Antibacterial Drug Discovery		521	(12)
Targeting the Resistance Mechanism		522	(1)
Extremely Narrow-Spectrum Drugs		523	(1)
Phage Therapies and other Bacteriolytic Approaches		524	(1)
Strategies for Reducing Virulence and/or Influencing Pathogenesis		525	(8)
Reverse Vaccinology: Revolutionizing the Approach to Vaccine Design		533	(22)
Laura Serino
Mariagrazia Pizza
Rino Rappuoli
Impact of Genomics on Vaccine Design		533	(2)
MenB Vaccine Approach by Reverse Vaccinology		535	(3)
Following the MenB Experience: Other Pathogens		538	(1)
Functional Genomics		539	(1)
Gene Expression In Vivo: IVET and STM		540	(1)
Transcriptome Analysis and Comparative Genomics		541	(5)
Proteomics and Vaccine Design		546	(1)
Conclusions		546	(9)
Index		555

Jorg Hacker studied biology and performed his doctoral thesis at the Martin-Luther-University of Halle in 1979. He was appointed as Associate Professor in the year 1988 and as Full Professor and Chair for Molecular Biology of Infectious Diseases at the University of Wurzburg in 1993. His research interests center on the analysis of pathogenic bacteria and their host organisms, and his laboratory described the first pathogenicity islands as early as the start of the nineties. Jorg Hacker is a member of numerous academies and scientific societies and holds positions on several research bodies. He has received many awards, and was made Honorary Doctor by the University of Umea, Sweden, in 2002 and by the University of Pecs, Hungary, in 2004. Ulrich Dobrindt graduated with a degree in biology from the University of Gottingen (1995) and a PhD in microbiology (1999) from the University of Wurzburg. He received a PhD scholarship from the Boehringer Ingelheim Fonds, and went on to carry out research on gene regulation in uropathogenic E. coli before becoming group leader of the Pathogenic Enterobacteria group at the Institute for Molecular Biology of Infectious Diseases working on enterobacterial genome plasticity focusing on extraintestinal pathogenic E. coli.