Legionella Pneumophila: Pathogenesis and Immunity (Infectious Agents and Pathogenesis)

217 Pages·2007·4.73 MB·English

by  Paul Hoffman

Legionella pneumophila:
Pathogenesis and Immunity
INFECTIOUS DISEASES AND PATHOGENESIS
Series Editors: Mauro Bendinelli, University of Pisa
Herman Friedman, University of South Florida College of Medicine
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ENTERIC INFECTIONS AND IMMUNITY
Edited by Lois J. Paradise, Mauro Bendinelli, and Herman Friedman
HELICOBACTER PYLORI INFECTION AND IMMUNITY
Edited by Yoshimasa Yamamoto, Herman Friedman, and Paul S. Hoffman
HERPESVIRUSES AND IMMUNITY
Edited by Peter G. Medveczky, Herman Friedman, and Mauro Bendinelli
HUMAN RETROVIRAL INFECTIONS
Immunological and Therapeutic Control
Edited by Kenneth E. Ugen, Mauro Bendinelli, and Herman Friedman
MICROORGANISMS AND AUTOIMMUNE DISEASES
Edited by Herman Friedman, Noel R. Rose, and Mauro Bendinelli
LEGIONELLA PNEUMOPHILA: PATHOGENESIS AND IMMUNITY
Edited by Paul Hoffman, Herman Friedman, and Mauro Bendinelli
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Legionella pneumophila:
Pathogenesis and Immunity
Paul Hoffman
Department of Microbiology Medicine,
Division of Infectious Diseases and International Health,
UVA Health System,
University of Virginia,
Charlottesville, VA, USA
Herman Friedman
College of Medicine,
University of South Florida,
Tampa, FL, USA
Mauro Bendinelli
University of Pisa, Italy
Paul Hoffman
University of Virginia,
Charlottesville, VA, USA
Herman Friedman
University of South Florida,
Tampa, FL, USA
Mauro Bendinelli
University of Pisa,
Pisa Italy
ISBN-13: 978-0-387-70895-9 e-ISBN-13: 978-0-387-70896-6
Library of Congress Control Number: 2007926437
©2008 Springer Science(cid:2)Business Media, LLC
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Dedication
We dedicate this book to the memory of Dr. Herman Friedman,
editor and friend, who passed away on August 25, 2007.
As scholar, scientist and teacher, he contributed broadly to the
disciplines of medical microbiology and immunology, but he will
be best remembered for his books, mentorship of young scientists
and for his seminal contributions to our knowledge of the
immunobiology of Legionnaires’ disease.
Contents
Preface and Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii
1. Legionella pneumophilaPathogenesis:
Lessons Learned from Genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
CHRISTEL CAZALET and CARMEN BUCHRIESER
1. Genomics of Legionella pneumophila . . . . . . . . . . . . . . . . . . . . . . . 1
1.1. General Features and Organization of the
L. pneumophilaGenomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2. Host–Pathogen Interaction—Specific Features
of the L. pneumophilaGenomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1. Eukaryotic-Like Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.2. Putative Virulence Factors as Deduced
Prom Sequence Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.3. Secretion Machineries—Presence of Particular
Many and a Wide Variety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
3. Metabolism as Deduced from the Genome Sequence . . . . . . . . . . . . 14
4. Clues to Adaptation—Regulation and Signal Transduction . . . . . . . 15
5. Comparative Genomics of Legionella pneumophila . . . . . . . . . . . . . 17
5.1. The Specific Gene Complements
of L. pneumophilaParis, Lens and Philadelphia . . . . . . . . . . . . 17
5.2. Genomic and Pathogenicity Islands . . . . . . . . . . . . . . . . . . . . . 18
5.3. Plasmids of Legionella . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
5.4. Variability at the Gene Level . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
6. Comparative Genomics— Legionella, Coxiella
and Other Intracellular Pathogens . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
6.1. Genome Comparison of Legionella pneumophila
and Coxiella burnetii . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
6.2. Genome Redundancy—Gene Family
Expansion in Legionella . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
7. Comparative Genomics of Legionella pneumophila
and the Genus Legionella —a Perspective . . . . . . . . . . . . . . . . . . . . 25
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
vii
viii Contents
2. Iron Assimilation and Type II Protein Secretion . . . . . . . . . . . . . . . . . . 33
NICHOLAS P. CIANCIOTTO
1. Iron Assimilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
1.1. The Importance of Iron for Legionella pneumophila . . . . . . . . 33
1.2. LegionellaSiderophores . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
1.3. Ferrous Iron Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
1.4. The L. pneumophilaIron Acquisition/Assimilation Locus . . . . 38
1.5. Cytochrome C Maturation and Iron Assimilation . . . . . . . . . . . 38
1.6. LegionellaFerric Reductases . . . . . . . . . . . . . . . . . . . . . . . . . . 39
1.7. Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
2. Type II Protein Secretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
2.1. Type II Protein Secretion in Gram-Negative Bacteria . . . . . . . 40
2.2. Discovery of Type II Secretion in Legionella pneumophila . . . 41
2.3. Factors Secreted by the Type II System of L. pneumophila . . . 42
2.4. Role of Type II Secretion in Pathogenesis . . . . . . . . . . . . . . . . 43
2.5. Role of Type II Secretion in Environmental Survival . . . . . . . . 44
2.6. Concluding Comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
3. The Dot/Icm Type IVB Secretion System . . . . . . . . . . . . . . . . . . . . . . . 49
JASON J. LEBLANC andJOSEPH P. VOGEL
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
2. Dot/Icm Type IV Secretion System . . . . . . . . . . . . . . . . . . . . . . . . . 50
2.1. Structural Components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
2.2. Adaptor/Chaperone Complexes . . . . . . . . . . . . . . . . . . . . . . . . 53
2.3. Regulation of Effector Export . . . . . . . . . . . . . . . . . . . . . . . . . . 54
3. Genetic Regulation of the Dot/Icm System . . . . . . . . . . . . . . . . . . . 54
4. Possible Effector Proteins and Associated Functions . . . . . . . . . . . . 55
4.1. RalF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
4.2. The Sid Family . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
4.3. LidA and SidM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
4.4. LepA and LepB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
4.5. Ylf and the Vips . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
5. Temporal Modulation of the LCV Surface . . . . . . . . . . . . . . . . . . . . 58
6. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
4. Life Cycle, Growth Cycles and Developmental Cycle
of Legionella pneumophila . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
RAFAEL A. GARDUÑO
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
2. The Life Cycle of L. pneumophilaas Currently Understood . . . . . . 66
2.1. Attachment and Invasion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Contents ix
2.2. Post-Internalization Events and Intracellular Growth . . . . . . . . 68
2.3. End of Replication and Exit . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
2.4. What Role Do Ciliates Play in the Life Cycle
of L. pneumophila? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
3. The Growth Cycles of L. pneumophila . . . . . . . . . . . . . . . . . . . . . . . 70
4. The Developmental Cycle of L. pneumophila . . . . . . . . . . . . . . . . . 72
4.1. Legionella pneumophilaDevelopment
Along the Extracellular Growth Cycle . . . . . . . . . . . . . . . . . . . 73
4.2. MIF: The Result of L. pneumophila
Intracellular Differentiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
4.3. The Central Role of MIFs in the Study
of L. pneumophilaVirulence . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
5. Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
5. Legionella in the Environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
BARRY S. FIELDS
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
2. The Distribution of Legionellaas a Function of Various
Detection Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
3. Natural Environments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
4. Man-Made Environments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
5. Interaction with Other Organisms . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
6. Association with Biofilms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
6. Regulation of the Legionella pneumophilaLife Cycle . . . . . . . . . . . . . 95
RACHEL L. EDWARDS andMICHELE S. SWANSON
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
2. Life Cycle of L. pneumophila . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
3. Broth Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
4. Amino Acid Availability Governs Differentiation . . . . . . . . . . . . . . 98
4.1. Pht Family of Transporters . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
4.2. Stringent Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
5. Evidence that Other Factors Trigger Differentiation . . . . . . . . . . . . 101
5.1. Acetyl-phosphate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
6. Transcriptional Control of Differentiation via Sigma Factors . . . . . 102
6.1. RpoS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
6.2. RpoN and FleQ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
6.3. FliA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
7. Post-Transcriptional Control of Differentiation . . . . . . . . . . . . . . . . 104
7.1. LetA/LetS Two-Component System . . . . . . . . . . . . . . . . . . . . . 104
7.2. Carbon Storage Regulatory (Csr) System . . . . . . . . . . . . . . . . . 105
7.3. Hfq and Small RNAs (sRNAs) . . . . . . . . . . . . . . . . . . . . . . . . . 106
x Contents
8. Regulation of the Dot/Icm Type IV Secretion System . . . . . . . . . . . 107
9. Genomic Methods of Studying Differentiation . . . . . . . . . . . . . . . . . 108
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
7. Microbial Physiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
PAUL S. HOFFMAN
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
2. Intracellular Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
3. Morphology, Ultrastructure, and Surface Proteins . . . . . . . . . . . . . 115
3.1. Envelope Structure and Lipopolysaccharide (LPS) . . . . . . . . 116
3.2. Outer Membrane Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
3.3. Secreted Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
3.4. Motility and Chemotaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
4. Respiratory Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
5. Central Intermediary Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . 119
6. Biosynthetic Capacity and Amino Acid Auxotrophies . . . . . . . . . . 123
7. Protection from Oxidative Stress . . . . . . . . . . . . . . . . . . . . . . . . . . 124
8. Heat Shock Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
9. Stationary Phase Genes and Cell Wall Assembly . . . . . . . . . . . . . . 127
10. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
8. Legionnaires’ Disease—Clinical Picture . . . . . . . . . . . . . . . . . . . . . . . . 133
THOMAS J. MARRIE
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
2. Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
3. Clinical Features of Legionnaires’ Disease . . . . . . . . . . . . . . . . . . . . 137
4. Diagnosis of LegionellaInfection . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
4.1. Routine Laboratory Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
4.2. Specific Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
5. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
6. Pontiac Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
7. Nosocomial Legionnaire’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . 143
8. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
9. Legionella pneumophila: Innate and Adaptive Immunity . . . . . . . . . . . 151
HERMAN FRIEDMAN, CATHERINE NEWTON
andTHOMAS KLEIN
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
2. LegionellaImmunogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
3. Innate Immunity to L. pneumophila . . . . . . . . . . . . . . . . . . . . . . . . . 153
4. Adaptive Immunity to L. pneumophilaInfection . . . . . . . . . . . . . . . 156