Razin Molecular Biology and Pathogenicity of Mycoplasmas

1. Auflage 2002
ISBN: 978-0-306-47606-8
Verlag: Kluwer Academic Publishers
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 574 Seiten

The recent sequencing of mycoplasma genomes has marked a turning point in the molecular genetic analysis of these microorganisms. Transcriptome and proteome analyses promise to provide the first definition of the total protein complement of a cell. The mycoplasma group includes the smallest known self-replicating organisms carrying the smallest number of genes. No wonder, therefore, that mycoplasmas have a special appeal to those interested in deciphering the minimal set of genes essential for life. Mycoplasma genomics facilitated better understanding of mycoplasma pathogenesis.

Most impressive are the findings concerning the interaction of mycoplasmas with the immune system, macrophage activation, cytokine induction, mycoplasma cell components acting as superantigens, and autoimmune manifestations. The molecular definition of mycoplasmal adhesins responsible for mycoplasma attachment to host cells and evasion of the host immune system by antigenic variation of mycoplasmal surface components are other `hot' subjects of research. Demonstration of the ability of mycoplasmas to enter host cells, cause fusogenic, apoptotic and oncogenic effects, as well as the possible association of mycoplasmas with arthritis, had their share in intensifying research on mycoplasma pathogenesis, bringing more researchers into the circle of those interested in this group of organisms. The present book is a comprehensive, up-to-date, multi-authored treatise.

Written for: Mycoplasmologists, molecular biologists, geneticists, bioinformatics researchers

Autoren/Hrsg.

Razin, Shmuel

Inhaltsverzeichnis

1;Preface;9
2;Contents;12
3;Chapter 1 Taxonomy of Mollicutes;15
3.1;1. INTRODUCTION;15
3.2;2. TAXONOMY;16
3.2.1;2.1 General concepts;16
3.2.2;2.2 The species concept;17
3.2.3;2.3 The Candidatus concept;19
3.3;3. PHYLOGENY;19
3.3.1;3.1 Some basic definitions;20
3.3.2;3.2 The 16S rRNA gene as a phylogenetic tool;20
3.3.3;3.3 Construction of phylogenetic trees;22
3.3.4;3.4 Taxonomy and phylogeny based on genes other than 16S rRNA;23
3.4;4. TAXONOMY AND PHYLOGENY OF THE;23
3.4.1;4.1 Taxonomy and phylogeny of the genus;26
3.4.2;4.2 Taxonomy and phylogeny of the genera Entomoplasma and Mesoplasma;31
3.4.3;4.3 Taxonomy and phylogeny of the genus;31
3.4.4;4.4 Taxonomy and phylogeny of the genera Acholeplasma, Anaeroplasma and Asteroleplasma;32
3.4.5;4.5 Taxonomy and phylogeny of the phytoplasmas;33
3.4.6;4.6 Taxonomy and phylogeny of the genus;33
3.5;5. THE USE OF 16S rRNA SEQUENCE DATA FOR DESCRIPTION OF NEW SPECIES;34
3.5.1;5.1 The relationship between 16S rRNA sequence data and DNA-DNA reassociation values;35
3.6;6. THE IMPACT OF WHOLE GENOME SEQUENCING ON TAXONOMY AND PHYLOGENY;36
3.7;7. CONCLUSIONS;37
3.8;ACKNOWLEDGMENTS;37
4;Chapter 2 Phylogeny and Evolution;44
4.1;1. INTRODUCTION;44
4.2;2. ANALYSIS OF 16S rRNA PHYLOGENETIC TREES;45
4.3;3. ORIGIN AND EVOLUTION OF THE MOLLICUTES;45
4.4;4. THE AAP PHYLOGENETIC BRANCH;49
4.5;5. THE SEM PHYLOGENETIC BRANCH;49
4.6;6. EVOLUTION OF MOLLICUTES GENOME SIZE;55
4.7;ACKNOWLEDGMENTS;55
4.8;REFERENCES;56
5;Chapter 3 Mycoplasmas of Humans;57
5.1;1. INTRODUCTION;57
5.2;2. CLINICAL SIGNIFICANCE;58
5.2.1;2.1 Many species are commensals;58
5.2.2;2.2 Respiratory diseases;59
5.2.3;2.3 Urogenital diseases;60
5.2.4;2.4 Neonatal infections;62
5.2.5;2.5 Arthritis and systemic infections in the immunocompromised patient;63
5.3;3. BIOLOGICAL FEATURES OF HUMAN MYCOPLASMAS RELEVANT TO PATHOGENICITY;66
5.3.1;3.1 Ureaplasma species;66
5.3.2;3.2 Mycoplasma hominis;69
5.3.3;3.3 Mycoplasma genitalium;70
5.3.4;3.4 Other mycoplasmas;71
5.4;REFERENCES;74
6;Chapter 4 Mycoplasmas of Animals;84
6.1;1. INTRODUCTION;84
6.2;2. MYCOPLASMAS OF RUMINANTS;86
6.2.1;2.1 Bovine mycoplasmas;86
6.2.2;2.2 Mycoplasmas of sheep, goats and wild caprinae;88
6.3;3. MYCOPLASMAS OF POULTRY;90
6.4;4. PORCINE MYCOPLASMAS;91
6.5;5. EQUINE MYCOPLASMAS;92
6.6;6. MYCOPLASMAS OF DOGS AND CATS;92
6.7;7. MYCOPLASMAS OF SMALL RODENTS;93
6.8;8. CONCLUSIONS;93
6.9;ACKNOWLEDGMENTS;94
6.10;REFERENCES;94
7;Chapter 5 Mycoplasmas of Plants and Insects;102
7.1;1. INTRODUCTION;102
7.2;2. PHYLOGENETIC DIVERSITY OF PLANT AND INSECT MYCOPLASMAS;103
7.3;3. DIVERSITY OF PHYTOPLASMAS AND SPIROPLASMAS;105
7.3.1;3.1 Biological and pathological diversity;105
7.3.2;3.2 Molecular diversity of phytoplasmas;109
7.3.3;3.3 Taxonomic and molecular diversity of spiroplasmas;116
7.4;4. CONCLUDING REMARKS;118
7.5;ACKNOWLEDGMENTS;119
7.6;REFERENCES;119
8;Chapter 6 Cell Division;127
8.1;1. INTRODUCTION;127
8.2;2. DIVISION MODE;127
8.3;3. DNA REPLICATION;128
8.4;4. SEGREGATION OF THE REPLICATED CHROMOSOME;130
8.5;5. DUPLICATION OF THE ATTACHMENT ORGANELLE;131
8.5.1;5.1 Scheme for migration of the attachment organelle;131
8.5.2;5.2 Formation of nascent organelle;133
8.6;6. CYTOSKELETAL STRUCTURES;134
8.7;7. CYTOKINESIS;134
8.7.1;7.1 Constriction;134
8.7.2;7.2 Gliding motility;135
8.7.3;7.3 Branch formation;136
8.8;8. PERSPECTIVES;136
8.9;ACKNOWLEDGMENTS;137
8.10;REFERENCES;137
9;Chapter 7 The Cell Membrane and Transport;141
9.1;1. INTRODUCTION;141
9.2;2. STRUCTURE AND FUNCTION OF MEMBRANE PROTEINS;142
9.2.1;2.1 General properties;142
9.2.2;2.2 Types and numbers of Mollicute proteins;143
9.2.3;2.3 Major membrane protein functions;145
9.3;3. MEMBRANE LIPID BILAYERS;154
9.3.1;3.1 Biosynthetic pathways: lipids, enzymes and genes;154
9.3.2;3.2 Regulation of lipid bilayer packing properties;159
9.4;4. CONCLUSIONS;164
9.5;ACKNOWLEDGEMENTS;164
9.6;REFERENCES;165
10;Chapter 8 Central Carbohydrate Pathways: Metabolic Flexibility and the Extra Role of Some “Housekeeping” Enzymes;172
10.1;1. INTRODUCTION;172
10.2;2. THE MOST ANCIENT WAY;172
10.3;3. BUT WHY GLUCOSE?;173
10.4;4. CARBOHYDRATE CATABOLISM;173
10.5;5. FUELS, THEIR PRIMING AND THEIR ENTRY INTO THE CELL;175
10.6;6. PRIMING ENTRY OF CARBOHYDRATE (GLUCOSE);176
10.7;7. GLUCOSE INSIDE THE CELL: ATP FORMATION AND THE INVOLVED PATHS TO OXYGEN AND PYRUVATE;177
10.8;8. THE INVOLVEMENT OF OXYGEN;178
10.9;9. THE CONTRIBUTORY ROLE OF THE THIOREDOXIN REDUCTASE SYSTEM;179
10.10;10. THE DIRECT ROUTE TO PYRUVATE;180
10.11;11. THE REVERSIBLE PPI-6PFK;180
10.12;12. THE ROLES OF PYROPHOSPHATE IN MOLLICUTES;181
10.13;13. NON-FERMENTATIVE MOLLICUTES: THEIR GLYCOLYTIC DEFICITS AND ROLE OF THE PENTOSE PHOSPHATE PATHWAY;182
10.14;14. BEYOND PHOSPHOFRUCTOKINASE TO PYRUVATE AND THE PYRUVATE “ROUNDHOUSE”;183
10.15;15. PHOSPHOGLYCERATE KINASE (PGK) AND PYRUVATE KINASE (PK);183
10.16;16. THE PYRUVATE “ROUNDHOUSE”;184
10.17;17. THE TCA CYCLE IS ABSENT IN MOLLICUTES BUT FOR MALATE DEHYDROGENASE;186
10.18;18. LINKAGE OF THE PPP AND EMP;187
10.19;19. THE ROLE OF THE PPP AND DEOYXRIBOSE-5-PHOSPHATE ALDOLASE IN MOLLICUTES;188
10.20;20. OTHER CARBOHYDRATE PATHS IN MOLLICUTES;189
10.21;21. METABOLIC TAXONOMY;190
10.22;22. PHYLOGENY, BUT NOT WITH rRNA;192
10.23;23. EPILOGUE: MYCOPLASMATALES?;196
10.24;ACKNOWLEDGMENTS;198
10.25;REFERENCES;198
11;Chapter 9 Database Systems for the Analysis of Biochemical Pathways;209
11.1;1. INTRODUCTION;209
11.2;2. BIOCHEMICAL DATABASES;210
11.2.1;2.1 General resources;211
11.2.2;2.2 Existing biochemical pathway specific resources;213
11.3;3. QUERYING AND EXTRACTING THE INFORMATION;215
11.3.1;3.1 Querying the data;215
11.3.2;3.2 Extracting the information for its use in your own project;216
11.4;4. PRINCIPLES FOR BUILDING YOUR OWN PATHWAY DATABASE;217
11.5;5. CONCLUSIONS;223
11.6;ACKNOWLEDGMENTS;224
11.7;REFERENCES;224
11.8;APPENDIX;226
12;Chapter 10 Mycoplasmas and the Minimal Genome Concept;229
12.1;1. MYCOPLASMAS AS SIMPLE MODEL CELLS;229
12.2;2. THE RANGE OF GENOME COMPLEXITY;230
12.3;3. WHAT IS A MINIMAL GENOME AND CAN IT BE DEFINED?;230
12.4;4. COMPARATIVE GENOMICS AND THE MINIMAL GENOME;232
12.5;5. EXPERIMENTAL APPROACHES TO DEFINING A MINIMAL GENOME;234
12.6;6. IMPLICATIONS OF THE PROPOSED MINIMAL GENE SETS;236
12.7;7. POTENTIAL APPLICATIONS OF MINIMAL GENOMES;237
12.8;ACKNOWLEDGMENTS;238
12.9;REFERENCES;238
12.10;APPENDIX;240
13;Chapter 11 Comparative Genome Analysis of the Mollicutes;262
13.1;1. OVERVIEW;262
13.2;2. EVOLVING MOLLICUTE ANNOTATION: THE EXAMPLE;266
13.3;3. EVOLVING METHODS FOR MOLLICUTE GENOME ANALYSIS: THE EXAMPLE;270
13.4;4. COMPARATIVE GENOME ANALYSIS TO DETECT FEATURES OF SPECIFIC MOLLICUTES;273
13.5;5. COMPARATIVE ANALYSIS TO REVEAL COMMON FEATURES OF MOLLICUTES;278
13.6;6. COMBINING GENOMIC FEATURES WITH BIOCHEMICAL KNOWLEDGE;281
13.7;REFERENCES;282
14;Chapter 12 Transcriptome and Proteome Analyses of Mollicutes;286
14.1;1. INTRODUCTION;286
14.1.1;1.1 Transcriptome analysis;287
14.1.2;1.2 Proteome analysis;289
14.1.3;1.3 Transcriptome versus proteome;291
14.2;2. THE TRANSCRIPTOME OF M. PNEUMONIAE;295
14.3;3. THE PROTEOME OF SPIROPLASMA MELLIFERUM;297
14.4;4. THE PROTEOME OF M. GENITALIUM;298
14.5;5. THE PROTEOME OF M. PNEUMONIAE;299
14.6;6. COMPARISON OF THE PROTEOMES OF M. GENITALIUM AND M. PNEUMONIAE;302
14.7;7. CONCLUSION;303
14.8;ACKNOWLEDGEMENTS;303
14.9;REFERENCES;304
15;Chapter 13 DNA Replication, Repair and Stress Response;310
15.1;1. INTRODUCTION;310
15.2;2. REPLICATION INITIATION;310
15.2.1;2.1 DnaA protein;311
15.2.2;2.2 Replication origin (oriC);311
15.3;3. REPLICATION FORKS;313
15.3.1;3.1 DNA polymerase III holoenzyme;314
15.3.2;3.2 Primosomal proteins;316
15.3.3;3.3 Proteins involved in sealing Okazaki fragments;316
15.3.4;3.4 Replication fork arrest and termination of DNA replication;317
15.4;4. OTHER PROTEINS INVOLVED IN DNA REPLICATION;318
15.4.1;4.1 Single-stranded DNA binding protein (SSB);318
15.4.2;4.2 Topoisomerases;318
15.5;5. DNA REPAIR AND STRESS RESPONSE;319
15.5.1;5.1 SOS stress response;319
15.5.2;5.2 Base excision repair;320
15.5.3;5.3 Nucleotide excision repair;321
15.5.4;5.4 Recombinational repair system;322
15.6;6. CONCLUSIONS;324
15.7;ACKNOWLEDGMENTS;324
15.8;REFERENCES;324
16;Chapter 14 Transcription and Translation;329
16.1;1. INTRODUCTION;329
16.2;2. GENERAL FEATURES OF MYCOPLASMA GENOMES AND GENES;330
16.3;3. TRANSCRIPTION;332
16.3.1;3.1 RNA polymerase;332
16.3.2;3.2 Promoters and transcription initiation;332
16.3.3;3.3 Termination and attenuation;333
16.3.4;3.4 Processing of RNA gene transcripts;334
16.3.5;3.5 Regulation;335
16.4;4. TRANSLATION;336
16.4.1;4.1 Ribosomes, translation factors and aminoacyl tRNA synthetases;336
16.4.2;4.2 Shine-Dalgarno sequence and translational initiation;337
16.4.3;4.3 Codon usage;338
16.4.4;4.4 tRNA anticodons and codon-recognition;340
16.4.5;4.5 UGA as a tryptophan codon;344
16.4.6;4.6 Translation in vivo and in vitro;345
16.4.7;4.7 tmRNA and trans-translation;345
16.5;REFERENCES;346
17;Chapter 15 Extrachromosomal Elements and Gene Transfer;352
17.1;1. INTRODUCTION;352
17.2;2. EXTRACHROSOMAL ELEMENTS;353
17.2.1;2.1 Plasmids;353
17.2.2;2.2 Viruses;354
17.3;3. GENE TRANSFER;357
17.3.1;3.1 Transformation;357
17.3.2;3.2 Selectable markers;359
17.3.3;3.3 Cloning and expression vectors;360
17.3.4;3.4 Transposon mutagenesis;363
17.3.5;3.5 Gene disruption through homologous recombination;365
17.3.6;3.6 Mycoplasma mating;367
17.4;4. CONCLUSIONS;368
17.5;ACKNOWLEDGMENTS;368
17.6;REFERENCES;368
18;Chapter 16 Restriction-Modification Systems and Chromosomal Rearrangements in Mycoplasmas;376
18.1;1. TYPES OF RESTRICTION-MODIFICATION;376
18.2;2. RESTRICTION-MODIFICATION SYSTEMS IN MYCOPLASMAS;378
18.2.1;2.1 Mycoplasma arthritidis;378
18.2.2;2.2 Mycoplasma pulmonis;379
18.3;3. RESTRICTION-MODIFICATION VIS-A-VIS MYCOPLASMA GENETICS;380
18.4;4. CHROMOSOMAL REARRANGEMENTS IN MYCOPLASMAS;381
18.4.1;4.1 Mycoplasmal speciation and chromosomal rearrangements;382
18.4.2;4.2 Recombination;383
18.4.3;4.3 Illegitimate recombination;387
18.4.4;4.4 Other instances of chromosomal rearrangements in mycoplasmas;389
18.5;REFERENCES;390
19;Chapter 17 Invasion of Mycoplasmas into and Fusion with Host Cells;396
19.1;1. INVASION INTO HOST CELLS;396
19.1.1;1.1 Experimental systems;396
19.1.2;1.2 Invasins and receptors;397
19.1.3;1.3 Changes in the host cell cytoskeleton;398
19.1.4;1.4 Signal transduction;399
19.1.5;1.5 Survival and multiplication within host cells;400
19.1.6;1.6 Cytopathic effects;400
19.2;2. FUSION WITH HOST CELLS;401
19.2.1;2.1 Factors mediating fusion;401
19.2.2;2.2 Molecules implicated in fusion;401
19.2.3;2.3 Role in virulence;403
19.3;3. CONCLUSIONS;403
19.4;REFERENCES;404
20;Chapter 18 Apoptotic, Antiapoptotic, Clastogenic and Oncogenic Effects;407
20.1;1. INTRODUCTION;407
20.2;2. THE NATURE OF CANCERS;407
20.3;3. APOPTOTIC AND ANTIAPOPTOTIC EFFECTS OF MYCOPLASMAS;408
20.3.1;3.1 Apoptotic effects;408
20.3.2;3.2 Mitogenic effects and antiapoptotic effects;410
20.4;4. CLASTOGENIC EFFECTS;411
20.5;5. ONCOGENIC EFFECTS;413
20.5.1;5.1 Acute form of induction;413
20.5.2;5.2 Chronic form of induction;414
20.6;6. MYCOPLASMAS AS A MODEL SYSTEM FOR CANCER RESEARCH;415
20.7;7. CONCLUSION;416
20.8;REFERENCES;417
21;Chapter 19 Genetic Mechanisms of Surface Variation;421
21.1;1. INTRODUCTION;421
21.2;2. FREQUENT MUTATIONS AS GENETIC SWITCHES;423
21.2.1;2.1 Mutations in regulatory elements;423
21.2.2;2.2 Mutations within coding regions;425
21.3;3. SITE-SPECIFIC DNA INVERSIONS AND PHENOTYPIC SWITCHING;427
21.3.1;3.1 The vsa gene system of Mycoplasma pulmonis;428
21.3.2;3.2 The vsp gene system of Mycoplasma bovis;429
21.3.3;3.3 Catalysis by site-specific recombinases;432
21.4;4. EXTENDED REPERTOIRES OF HOMOLOGOUS GENES ENCODING VARIABLE SURFACE ANTIGENS;433
21.4.1;4.1 vlp gene repertoire of M. hyorhinis;433
21.4.2;4.2 vsp gene repertoire of M. bovis;434
21.5;5. OTHER MECHANISMS OF SURFACE VARIATION;434
21.5.1;5.1 Generation of chimeric vsp genes by intragenic recombination in M. bovis;434
21.5.2;5.2 Generation of chimeric genes by multiple gene conversions: the vlhA system of Mycoplasma synoviae;435
21.5.3;5.3 Transcriptional effects determine variable P35 expression in Mycoplasma penetrans;437
21.5.4;5.4 Repetitive DNA and antigenic variation in Mycoplasma genitalium and Mycoplasma pneumoniae;437
21.6;6. EFFECTS OF VARIABLE PRODUCTS: SURFACE ARCHITECTURE AND EXOPROTEIN MODIFICATION;438
21.6.1;6.1 Surface phenotypes affected by phase-variable masking;438
21.6.2;6.2 Size variation;439
21.6.3;6.3 Posttranslational modification and variable release of exoproteins;440
21.6.4;ACKNOWLEDGMENTS;441
21.6.5;REFERENCES;441
22;Chapter 20 Immunomodulation by Mycoplasmas: Artifacts, Facts and Active Molecules;448
22.1;1. MISHAPS AND MISINTERPRETATIONS;448
22.1.1;1.1 Mycoplasmas and malaria;449
22.1.2;1.2 Mycoplasmas and natural killer (NK) cells;450
22.1.3;1.3 Mycoplasmas and T cell glycolipids;450
22.1.4;1.4 Mycoplasmas and “lymphokines” which activate B cells to proliferate and produce immunoglobulins;450
22.1.5;1.5 Mycoplasmas and a differentiation-inducing cytokine;450
22.1.6;1.6 Mycoplasmas and nonself discrimination of malignant cells;452
22.1.7;1.7 Mycoplasmas and a cytotoxicity inducing activity;452
22.2;2. CAUSE AND EFFECTS;453
22.2.1;2.1 Earlier reports on immunomodulation by mycoplasmas;454
22.3;3. MYCOPLASMAL LIPOPROTEINS AND LIPOPEPTIDES AS IMMUNOMODULATORY COMPONENTS;455
22.3.1;3.1 Pioneer work;455
22.3.2;3.2 Mycoplasmal lipoproteins;455
22.3.3;3.3 MALP-2, the molecule;456
22.3.4;3.4 Structural details that determine the biological activity of MALP-2;458
22.3.5;3.5 Structural similarities between macrophageactivating lipopeptides and LPS endotoxins;459
22.3.6;3.6 Biological activities of MALP-2 and other mycoplasmal lipoproteins;460
22.3.7;3.7 Receptors and signal transduction;463
22.4;4. IMMUNOMODULATION BY MYCOPLASMAL PRODUCTS NOT DUE TO MACROPHAGE ACTIVATION;465
22.4.1;4.1 Activation of complement;465
22.4.2;4.2 Interaction of mycoplasmal compounds with bone organ cultures;465
22.4.3;4.3 Interaction of mycoplasmal compounds with cells of the nervous system;466
22.4.4;4.4 Effects of MALP-2 and other mycoplasmal compounds on fibroblasts and alveolar type II lung epithelial cells;466
22.5;5. SUMMARY AND CONCLUSIONS;466
22.6;ACKNOWLEDGMENTS;467
22.7;REFERENCES;468
23;Chapter 21 Mycoplasma arthritidis Pathogenicity: Membranes, MAM, and MAV1;476
23.1;1. INTRODUCTION;476
23.2;2. DISEASE;477
23.2.1;2.1 Rats;477
23.2.2;2.2 Mice;478
23.2.3;2.3 Rabbits;479
23.3;3. PATHOGENIC MECHANISMS IN MURINE ARTHRITIS;480
23.3.1;3.1 Membranes;480
23.3.2;3.2 MAM;482
23.3.3;3.3 MAV1;485
23.4;4. MODEL OF PATHOGENESIS FOR RATS;486
23.5;REFERENCES;487
24;Chapter 22 Cytadherence and the Cytoskeleton;493
24.1;1. INTRODUCTION;493
24.1.1;1.1 The attachment organelle;493
24.1.2;1.2 The cytoskeleton;493
24.2;2. THE ATTACHMENT ORGANELLE AND CELL DIVISION;495
24.3;3. ATTACHMENT ORGANELLE PROTEINS;495
24.3.1;3.1 Introduction;495
24.3.2;3.2 The P1 adhesin;496
24.3.3;3.3 ORF6 gene products;498
24.3.4;3.4 Protein P65;499
24.3.5;3.5 Protein P30;501
24.3.6;3.6 HMW3;503
24.3.7;3.7 HMW1;504
24.3.8;3.8 HMW2 and P28;506
24.3.9;3.9 Protein P200 as a candidate attachment organelle protein;509
24.3.10;3.10 Order of attachment organelle assembly;509
24.4;4. OTHER COMPONENTS OF THE MYCOPLASMA CYTOSKELETON;510
24.4.1;4.1 TX partitioning of Mycoplasma proteins;510
24.4.2;4.2 Identification of Mycoplasma cytoskeletal proteins;511
24.5;5. THE NATURE OF THE MYCOPLASM A CYTOSKELETON;512
24.5.1;5.1 Biochemical definition of the cytoskeleton;512
24.5.2;5.2 Physiological definition of the cytoskeleton;513
24.5.3;5.3 Defining the Mycoplasma cytoskeleton;513
24.6;6. CONCLUSION;514
24.7;ACKNOWLEDGMENTS;514
24.8;REFERENCES;515
25;Chapter 23 Mycoplasma pneumoniae Disease Manifestations and Epidemiology;521
25.1;1. INTRODUCTION;521
25.2;2. THE AGENT’S HISTORY AND ITS RESERVOIR;522
25.3;3. EPIDEMIOLOGY;524
25.4;4. MANIFESTATIONS OF DISEASES;527
25.5;REFERENCES;529
26;Diagnosis of Mycoplasmal Infections;533
26.1;1. INTRODUCTION;533
26.2;2. CULTURAL PROPERTIES AND BIOCHEMICAL TESTS;533
26.3;3. SEROLOGICAL TESTS;535
26.4;4. MOLECULAR GENETIC METHODS;537
26.4.1;4.1 Restriction endonuclease analysis (REA);537
26.4.2;4.2 PCR-based diagnostic procedures;538
27;Chapter 25 Antimycoplasmal Agents;547
27.1;1. INTRODUCTION;547
27.2;2. ANTIMICROBIAL SUSCEPTIBILITY TESTING;547
27.2.1;2.1 Broth dilution methods;548
27.2.2;2.2 Agar dilution and gradient diffusion methods;549
27.2.3;2.3 Minimal bactericidal concentration (MBC) tests;550
27.2.4;2.4 Interpretation of results;550
27.3;3. INNATE ANTIBIOTIC RESISTANCE OF MYCOPLASMAS;551
27.3.1;3.1 Resistance related to the class;551
27.3.2;3.2 Resistance related to the species;551
27.4;4. ANTIBIOTICS USED FOR TREATMENT OF MYCOPLASMAL INFECTIONS;553
27.4.1;4.1 Tetracyclines;554
27.4.2;4.2 Macrolide-Lincosamide-Streptogramin (MLS) group;555
27.4.3;4.3 Fluoroquinolones;556
27.4.4;4.4 Miscellaneous;557
27.5;5. ACQUIRED RESISTANCE OF MYCOPLASMAS;557
27.5.1;5.1 Tetracyclines;558
27.5.2;5.2 MLS group;559
27.5.3;5.3 Fluoroquinolones;560
27.5.4;5.4 Aminoglycosides;561
27.5.5;5.5 Chloramphenicol;562
27.6;6. CONCLUSION;562
27.7;REFERENCES;562
28;Index;569

Leseproben

Chapter 9
Database Systems for the Analysis of Biochemical Pathways (p. 201-202)

ISABEL ROJAS-MUJICA* and ERICH BORNBERG-BAUER#
*European Media Laboratory, Heidelberg, Germany,
#UMBER - Bioinformatics Group, School of Biological Sciences, University of Manchester, UK

1. INTRODUCTION

The mycoplasmas were amongst the first organisms for which the complete genome sequence was obtained and made available to the public domain (13, 10, 6). Complementary information, such as the proteome of mycoplasma pneumoniae (26) and reconstructed pathways, has also been made available and can be queried or downloaded from various locations on the web. However, database systems that allow scientists to work with these data in an integrated manner, together with other relevant information, are still not common. This is a wide-spread problem that not only applies to mycoplasma. Current biological research uses a wide range of interacting software which in turn uses a large number of disparate data source. These problems have arisen for several reasons which are, amongst others, the specialisation of biological disciplines, the lack of unified interfaces and the variations in the interpretation of the data, Bioinformatic tools need to overcome these difficulties. For biochemical pathways this implies the development of a system which is based on the functional roles of molecular objects such as reactions and pathways.

From a data modelling point of view the modelling of biochemical processes is a complex problem. Fuzziness of the definitions, exceptions and complex relations, are some of the common characteristics that are found when attempting to model these processes. Models for storage and representation of pathways and data on expression and the genome, must reflect the logics of the cellular machinery. At the same time they must be designed to offer a platform for optimal storage, retrieval and analysis of such data for the biological researcher. In this chapter, we provide an overview of available data resources and relevant tools for extracting pathway-related information from the most widely used databases and briefly explain their usage. We will also discuss some of the systems and methods, both established and new, to support the process of examination and understanding of the data. We will revise several of the methods and problems related to the integration, handling and interpretation of biochemical data. As an introduction to data modelling, we present a small example related to the modelling of enzymatic reactions. This is meant to raise awareness of the importance of structuring data. It should give researchers, who have no experience in creating databases, a rough idea of what they could gain from putting their data into an integrated system.

2. BIOCHEMICAL DATABASES

The genomes of Mycoplasma pneumoniae (M.pn.) and Mycoplasma genitalium (M.gen.) are widely viewed as a blueprint for a cell with a minimal metabolism. The availability of data generated from the sequencing of their genomes and results from both comparative genome analysis and experiments, such as global transposon mutagenesis (14), make them a sensible choice to study methods for pathway analysis and data integration. There are several databases – accessible through the World Wide Web (WWW) – that contain information about biochemical pathways, to different extends and with different focuses (see Appendix). With the growing amount of information related to biochemical reactions and thus with the growing interest towards the study of biochemical networks, the number of projects and databases (or data collections)i dealing with biochemical pathways is rapidly expanding. This means that, like any other study, this short description of some of the existing biochemical pathway databases can only be a snapshot of the current stand. We will mention a few of these databases, not all of which contain explicit information about mycoplasmas.