Cover
Contributors
Preface
About the Editors
I: Cellular Microbiology in the Study of Tissue and Organ Infections
1. 1 Interaction between Intracellular Bacterial Pathogens and Host Cell Mitochondria
  1. INTRODUCTION
  2. CYTOSOLIC BACTERIA
  3. VACUOLAR BACTERIA
  4. CONCLUSIONS
  5. REFERENCES
2. 2 Shigella Pathogenesis
  1. SHIGELLA AND SHIGELLOSIS
  2. THE SHIGELLA INFECTIOUS CYCLE
  3. SHIGELLA T3SS AND T3SS EFFECTORS
  4. SHIGELLA OVERCOMES THE PHYSICOCHEMICAL BARRIERS OF THE HOST AND THE GUT MICROBIOTA TO REACH THE COLONIC EPITHELIUM
  5. SHIGELLA INVADES COLONOCYTES AND ELICITS HELP FROM THE HOST TO REACH THE EPITHELIUM
  6. SHIGELLA LIKELY TRAVERSES THE COLONIC EPITHELIUM THROUGH M CELLS
  7. SHIGELLA ESCAPES MACROPHAGES BY INDUCING PYROPTOSIS
  8. ADHESION AND FORCED ENTRY INTO NONPHAGOCYTIC HOST CELLS
  9. PHAGOSOMAL ESCAPE OF SHIGELLA FLEXNERI
  10. SURVIVAL OF SHIGELLA FLEXNERI IN EPITHELIAL CELLS
  11. MAINTENANCE OF THE EPITHELIAL CELL CYTOSOLIC REPLICATIVE NICHE
  12. REPLICATION OF SHIGELLA IN THE EPITHELIAL CELL CYTOSOL
  13. SHIGELLA-MEDIATED SUBVERSION OF HOST INFLAMMATORY RESPONSES
  14. SHIGELLA SUBVERTS HOST ADAPTIVE IMMUNITY
  15. THE COMPLEXITY OF SHIGELLA PATHOGENESIS
  16. REFERENCES
3. 3 The Interplay between Salmonella enterica Serovar Typhimurium and the Intestinal Mucosa during Oral Infection
  1. INTRODUCTION
  2. INFECTION KINETICS OF S. TYPHIMURIUM IN THE STREPTOMYCIN-PRETREATED MOUSE MODEL
  3. INNATE MUCOSAL DEFENSE MECHANISMS
  4. DOWNSTREAM ELICITATION OF OVERT MUCOSAL INFLAMMATION
  5. AVOIDING RECOGNITION BY MODULATING THE HOST’S INNATE IMMUNE RESPONSE
  6. DIFFERENT VIRULENCE PHENOTYPES ARE REQUIRED AT EACH STEP OF GUT TISSUE INFECTION
  7. DISCUSSION AND OUTLOOK
  8. REFERENCES
4. 4 New Age Strategies To Reconstruct Mucosal Tissue Colonization and Growth in Cell Culture Systems
  1. INTRODUCTION: THE STUDY OF HOST-PATHOGEN INTERACTIONS IN CULTURE
  2. DEVELOPMENT OF INTESTINAL ORGANOIDS
  3. USE OF INTESTINAL ORGANOIDS FOR THE STUDY OF HOST-PATHOGEN INTERACTIONS
  4. ENGINEERING ADVANCES THAT HAVE IMPROVED THE INVESTIGATION OF HOST-PATHOGEN INTERACTIONS
  5. CONCLUSIONS
  6. REFERENCES
5. 5 The Many Faces of Bacterium-Endothelium Interactions during Systemic Infections
  1. THE ENDOTHELIUM AS A SITE OF BACTERIAL INFECTIONS
  2. CELLULAR JUNCTIONS AS THE GATEKEEPERS OF THE ENDOTHELIAL BARRIER
  3. ALTERATION OF VASCULAR INTEGRITY UPON INFECTION BY RICKETTSIA
  4. VASCULAR COLONIZATION AND BLOOD-BRAIN BARRIER CROSSING BY NEISSERIA MENINGITIDIS
  5. ALTERATION OF THE ENDOCARDIUM AND ENDOCARDITIS
  6. ANGIOPROLIFERATION DURING BARTONELLA INFECTIONS
  7. SYSTEMIC IMPLICATIONS OF VASCULAR INFECTIONS
  8. CONCLUDING REMARKS
  9. REFERENCES
6. 6 Reaching the End of the Line
  1. INTRODUCTION
  2. UROGENITAL TRACT
  3. INFECTION OF THE URINARY TRACT
  4. UTI PATHOGENESIS
  5. TREATMENT STRATEGIES FOR UROGENITAL INFECTIONS
  6. CONCLUSION
  7. REFERENCES
7. 7 The Intracellular Life Cycle of Brucella spp.
  1. THE BRUCELLA INTRACELLULAR CYCLE
  2. CONCLUDING REMARKS
  3. REFERENCES
8. 8 Infect and Inject: How Mycobacterium tuberculosis Exploits Its Major Virulence-Associated Type VII Secretion System, ESX-1
  1. INTRODUCTION
  2. THE ESX-1 SECRETION SYSTEM AND ITS PROTEINACEOUS ARMY
  3. DO OTHER BACTERIA HAVE ESX-1 SECRETION SYSTEMS?
  4. PRACTICAL IMPLICATIONS OF ESX-1
  5. CONCLUDING REMARKS
  6. REFERENCES
9. 9 Mycobacterium tuberculosis
  1. INTRODUCTION
  2. THE IMMUNE ENVIRONMENT AT THE SITE OF INFECTION
  3. LIFE OR DEATH IN THE PHAGOCYTE
  4. UNDERLYING MECHANISMS OF IMMUNE CONTROL AND DISEASE PROGRESSION
  5. IMs AND AMs ADOPT MARKEDLY DIFFERENT METABOLIC STATES IN RESPONSE TO M. TUBERCULOSIS INFECTION
  6. BASIS OF THE DIFFERENCE BETWEEN AMs AND IMs
  7. BACTERIAL METABOLISM IN THE HOST ENVIRONMENT
  8. COUPLED METABOLISM OF HOST AND PATHOGEN
  9. CONCLUDING REMARKS
  10. REFERENCES
10. 10 The Wolbachia Endosymbionts
  1. INTRODUCTION
  2. GENETIC DIVERSITY AMONG WOLBACHIA ENDOSYMBIONTS
  3. THE GREAT MANIPULATORS OF REPRODUCTION
  4. ROUTES CLOSING THE CIRCLE OF VERTICAL TRANSMISSION (SOMA TO GERM LINE)
  5. WOLBACHIA ARE NOT PASSIVE PASSENGERS OF THE GERM LINE
  6. THE INFLUENCE OF WOLBACHIA ON HOST METABOLISM AND FITNESS, AND BIOMEDICAL APPLICATIONS
  7. THE INTRACELLULAR LIFESTYLE OF WOLBACHIA
  8. CONCLUSION
  9. REFERENCES
11. 11 Make It a Sweet Home
  1. INTRODUCTION
  2. THE MAKING OF THE INCLUSION
  3. TRANSPORT TO THE INCLUSION
  4. CONCLUSION
  5. REFERENCES
12. 12 Salmonella Single-Cell Metabolism and Stress Responses in Complex Host Tissues
  1. INTRODUCTION
  2. SINGLE-CELL ANALYSIS OF PATHOGENS DURING INFECTION
  3. SYSTEMIC SALMONELLOSIS AS A MODEL
  4. SALMONELLA-HOST INTERACTIONS IN INFECTED SPLEEN
  5. ANTIBIOTIC ACTION IN VIVO
  6. OPEN QUESTIONS AND MAJOR CHALLENGES
  7. REFERENCES
13. 13 Manipulation of Host Cell Organelles by Intracellular Pathogens
  1. INTRODUCTION
  2. MEMBRANE TRANSPORT: A BRIEF OVERVIEW
  3. PHAGOCYTOSIS
  4. PCVs THAT RESIDE IN THE ENDOCYTIC PATHWAY
  5. DIVERGENCE FROM THE ENDOCYTIC PATHWAY AND MANIPULATION OF THE SECRETORY PATHWAY
  6. MAINTENANCE OF THE PCV
  7. CONCLUSION
  8. REFERENCES
II: Subcellular Microbiology
1. 14 The Role of the Type III Secretion System in the Intracellular Lifestyle of Enteric Pathogens
  1. INTRODUCTION
  2. S. TYPHIMURIUM AND LIFE IN THE SALMONELLA-CONTAINING VACUOLE: ROLE OF THE T3SS IN VACUOLE BIOGENESIS AND MAINTENANCE
  3. S. FLEXNERI AND LIFE IN THE HOST CYTOSOL: ROLE FOR T3SS IN VACUOLE ESCAPE
  4. V. PARAHAEMOLYTICUS: AN INTRACELLULAR BACTERIUM REVEALING NEW MECHANISMS FOR SURVIVAL AND REPLICATION
  5. CONCLUSIONS
  6. REFERENCES
2. 15 Customizing Host Chromatin
  1. INTRODUCTION
  2. HISTONE MODIFICATIONS IN RESPONSE TO BACTERIAL PRODUCTS
  3. BACTERIAL EFFECTORS TARGETING HISTONE MODIFICATIONS THROUGH SIGNALING EVENTS
  4. BACTERIAL FACTORS MIMICKING HOST CHROMATIN-MODIFYING ENZYMES
  5. BACTERIAL TARGETING OF DNA
  6. CONCLUSIONS AND PERSPECTIVES
  7. REFERENCES
3. 16 Cell Biology of Intracellular Adaptation of Mycobacterium leprae in the Peripheral Nervous System
  1. INTRODUCTION
  2. MYCOBACTERIUM LEPRAE AS A MODEL FOR NEUROPATHOGENESIS
  3. SIGNIFICANCE OF MODELING M. LEPRAE INTERACTION
  4. CONTRIBUTION OF BACTERIAL FACTORS TO NEURAL TROPISM
  5. SCHWANN CELL SIGNALING PATHWAYS ACTIVATED BY M. LEPRAE
  6. M. LEPRAE-INDUCED DEMYELINATION OF SCHWANN CELLS
  7. M. LEPRAE REPROGRAMMING OF SCHWANN CELLS
  8. CONCLUDING REMARKS
  9. REFERENCES
4. 17 Multifaceted Roles of MicroRNAs in Host-Bacterial Pathogen Interaction
  1. INTRODUCTION
  2. miRNA RESPONSE TO BACTERIAL INFECTION
  3. PERSPECTIVES
  4. REFERENCES
5. 18 Modulation of Host Cell Metabolism by Chlamydia trachomatis
  1. INTRODUCTION
  2. GLOBAL CHANGES IN HOST CELL METABOLISM
  3. CARBOHYDRATE METABOLISM
  4. MITOCHONDRIA AT THE CROSSROAD OF METABOLISM AND APOPTOSIS INHIBITION
  5. CONCLUSION: EXPLOITING HOST METABOLISM CHANGES FOR HOST-DIRECTED THERAPY
  6. REFERENCES
III: Autonomous Defense Pathways in the Cell
1. 19 Host-Encoded Sensors of Bacteria
  1. INTRODUCTION
  2. BACTERIAL MOLECULES THAT INDUCE HOST DEFENSE
  3. HOST-ENCODED SENSORS OF BACTERIAL MOLECULES
  4. HOST-ENCODED SENSORS OF PATHOGEN ACTIVITIES
  5. NEUTROPHIL RECRUITMENT TO THE SITES OF INFECTION—A COMMON OUTCOME OF BACTERIAL DETECTION
  6. PERSPECTIVES
  7. REFERENCES
2. 20 Recognition of Intracellular Bacteria by Inflammasomes
  1. INTRODUCTION
  2. INFLAMMASOME-FORMING SENSORS
  3. ANTIMICROBIAL FUNCTION OF PYROPTOSIS
  4. REFERENCES
IV: New Technologies To Move Cellular Microbiology to Organs and Tissues
1. 21 Modeling Infectious Diseases in Mice with a “Humanized” Immune System
  1. DEVELOPMENT OF IMMUNODEFICIENT MOUSE STRAINS
  2. APPROACHES TO GENERATE HIS MICE
  3. USING HUMAN IMMUNE SYSTEM MICE TO UNDERSTAND THE BIOLOGY OF BACTERIAL INFECTIONS
  4. CONCLUDING REMARKS
  5. REFERENCES
2. 22 A Cinematic View of Tissue Microbiology in the Live Infected Host
  1. INTRAVITAL MICROSCOPY AS A KEY MEDIATOR OF TISSUE MICROBIOLOGY
  2. THE INFECTIOUS MICROENVIRONMENT IN VIVO
  3. PHYSIOLOGICALLY RELEVANT INFECTION MODELS FOR TISSUE MICROBIOLOGY
  4. HUMANIZED MODELS: THE NEXT STEP IN TRANSLATIONAL RESEARCH
  5. TECHNOLOGICAL ADVANCEMENT TO MEET DEVELOPING NEEDS
  6. CONCLUSIONS
  7. REFERENCES
3. 23 Cellular Imaging of Intracellular Bacterial Pathogens
  1. INTRODUCTION
  2. MICROSCOPY AND FLUORESCENCE
  3. FLUORESCENT PROBES
  4. IMAGING-BASED SCREENING
  5. CORRELATIVE LIGHT AND EM OF LARGE VOLUMES
  6. THE NEXT CHALLENGES
  7. REFERENCES
4. 24 Using a Systems Biology Approach To Study Host-Pathogen Interactions
  1. INTRODUCTION
  2. IMPACT OF WHOLE REFERENCE GENOMES FOR PATHOGENS AND HOSTS
  3. CONCLUSIONS
  4. REFERENCES
Index
End User License Agreement

List of Tables

Chapter 3
1. TABLE 1 S. Typhimurium virulence factors that modulate the host immune response
2. TABLE 2 Examples of host response-modulating virulence factors of a variety o...
Chapter 6
1. TABLE 1 S. Virulence factors in UPEC pathogenesis
Chapter 7
1. TABLE 1 Brucella T4SS effectors
Chapter 11
1. TABLE 1 Identified Inc-host interactions
Chapter 14
1. TABLE 1 SPI-1 and SPI-2 effectors that contribute to the intracellular life c...
2. TABLE 2 Virulence factors that contribute to the intracellular life cycle ofS...
Chapter 17
1. TABLE 1 Host cell miRNAs regulated upon infection by bacterial pathogens^a
Chapter 19
1. TABLE 1 Mammalian PRRs and their targets^a

List of Illustrations

Chapter 1
1. Figure 1 Strategies of intracellular bacteria to interfere with mitochondria...
2. Figure 2 Relationship between extracellular bacteria and host cell mitochond...
Chapter 2
1. Figure 1 Shigella pathogenesis. Shigella infects the colonic epithelium at t...
2. Figure 2 Shigella T3SS and effectors. (A) Expression of the T3SS apparatus a...
3. Figure 3 Shigella subversion of host cell survival, integrity, and function....
4. Figure 4 Shigella modulation of antimicrobial defenses and proinflammatory r...
Chapter 3
1. Figure 1 Innate defense mechanisms in naive and S. Typhimurium (12 h)-infect...
2. Figure 2 Different S. Typhimurium phenotypes are required at different stage...
Chapter 4
1. Figure 1 Methods for using intestinal organoids to study host-pathogen inter...
2. Figure 2 Method for development of a 3D silk scaffold to model human intesti...
3. Figure 3 Method for development of the intestine chip using enteroids to mod...
Chapter 5
1. Figure 1 Schematic representation of the two main types of intercellular jun...
2. Figure 2 Infection of the endothelium by Rickettsia. Following bacterial ino...
3. Figure 3 Vascular colonization by N. meningitidis. Once in the bloodstream,
4. Figure 4 The stepwise process leading to endocarditis. The appearance of ste...
5. Figure 5 Bartonella-induced angioproliferation. Interactions of Bartonella w...
Chapter 6
1. Figure 1 UPEC pathogenesis. (A) UPEC is housed in a reservoir in the gastroi...
2. Figure 2 Overview of UPEC fitness and virulence factors. Surface-associated ...
3. Figure 3 Overview of CUP of pilus assembly and mode of action of antivirulen...
Chapter 7
1. Figure 1 Model of the Brucella intracellular cycle in macrophages. Following...
2. Figure 2 Structure and membrane composition of BCVs during the Brucella intr...
3. Figure 3 Model of VirB T4SS-dependent biogenesis of the rBCV. Bacteria in eB...
Chapter 8
1. Figure 1 Schematic of the ESX-1 secretion system. (A) Gene map of the esx-1 ...
2. Figure 2 ESX-1-related disease progression within the lung. Steps involved i...
3. Figure 3 TB vaccines in the pipeline, undergoing phase 1 to 3 clinical trial...
Chapter 9
1. Figure 1 (A) Schematic illustration of the potential outcomes of infection w...
2. Figure 2 Usefulness of the hspX′::GFP reporter strain in assessing and repor...
3. Figure 3 Selective depletion of AMs and IMs results in a decrease and an inc...
4. Figure 4 Models of macrophage reprogramming and preprogramming. How macropha...
5. Figure 5 Major classes of cholesterol-dependent anti-M. tuberculosis compoun...
6. Figure 6 M. tuberculosis infection leads to retention of the foamy macrophag...
Chapter 10
1. Figure 1 Overview of Wolbachia diversity. (A) Unrooted phylogenic tree of th...
2. Figure 2 The four reproductive outcomes caused by Wolbachia, with an example...
3. Figure 3 Germ line tropism and Wolbachia transmission in insect and nematode...
Chapter 11
1. Figure 1 Cells infected with C. trachomatis for 24 h (top left) and 48 h (to...
2. Figure 2 Pathways for the import of molecules in the membrane and lumen of t...
Chapter 12
1. Figure 1 A paradigm shift in pathogen analysis in host tissues. (a) Common m...
2. Figure 2 Working model for Salmonella-host interactions in an infected splee...
Chapter 13
1. Figure 1 Rab GTPase signature of PCVs that interact with the endocytic pathw...
2. Figure 2 Rab GTPase signature of PCVs that diverge from the endocytic pathwa...
Chapter 14
1. Figure 1 Schematic of the contribution of T3SS effectors to the intracellula...
2. Figure 2 Schematic of the contribution of virulence factors to the intracell...
3. Figure 3 Schematic of the V. parahaemolyticus intracellular life cycle and t...
Chapter 15
1. Figure 1 Nuclear effectors targeting histone marks. Secreted effectors from
2. Figure 2 SET domain effectors mediate histone methylation. Effectors of C. t...
3. Figure 3 Targeting host DNA. Genotoxins such as CDT and colibactin induce ho...
Chapter 16
1. Figure 1 The adult nervous system comprises the PNS and CNS. The CNS is conn...
2. Figure 2 (A) Functional units of the adult human peripheral nerves, i.e., my...
3. Figure 3 Molecular basis of neural tropism of M. leprae. Interaction of M. l...
4. Figure 4 Schwann cell receptors α/β-dystroglycan and receptor tyrosine kinas...
5. Figure 5 In vivo induction of demyelination by direct M. leprae injection in...
6. Figure 6 Proposed model of how adult Schwann cell reprogramming to stem cell...
Chapter 17
1. Figure 1 Overview of the canonical miRNA biogenesis pathway. miRNA genes are...
2. Figure 2 Regulation of miRNAs upon infection by bacterial pathogens impacts ...
3. Figure 3 Mycobacterium spp.-induced miRNA changes have a strong impact on au...
Chapter 18
1. Figure 1 Distribution and overrepresentation of validated hits of the human ...
2. Figure 2 Pathway map representing modulated metabolites and related host fac...
3. Figure 3 Regulation of glucose metabolism and mitochondrial architecture in
Chapter 19
1. Figure 1 Evolutionary arms race between the host immune system and bacterial...
Chapter 20
1. Figure 1 Activation of canonical and noncanonical inflammasomes by bacteria....
2. Figure 2 Antimicrobial effects of pyroptosis. (A) Activation of canonical or...
Chapter 21
1. Figure 1 Timeline for development of immunodeficient mouse strains that form...
2. Figure 2 Boosting immune subsets in humanized mice. Cytokines and growth fac...
3. Figure 3 Studying human pathogens in humanized mice. A variety of human path...
Chapter 22
1. Figure 1 Tissue microbiology. (A) Schematic illustration of the development ...
2. Figure 2 Multiphoton imaging of bacterial infections. (A, B) Uropathogenic E...
3. Figure 3 Staining of Salmonella (green) biofilm extracellular matrix by lumi...
Chapter 23
1. Figure 1 Wavelengths, objects, and their recognition. The sizes of different...
2. Figure 2 The Jablonski diagram explains the basic principles of fluorescence...
3. Figure 3 Fixed confocal acquisition of ruffle formations and Salmonella entr...
4. Figure 4 Time-lapse imaging of epithelial cells infected with Salmonella usi...
5. Figure 5 Statistical tools for imaging-based screens. (A) Statistical analys...
6. Figure 6 Large-volume CLEM workflow via multidimensional confocal and FIB/SE...
Chapter 24
1. Figure 1 Potential pathways to the functional analysis and exploitation of p...
2. Figure 2 How genomics can empower a clinical sample. It is possible to colle...

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Library of Congress Cataloging-in-Publication Data

Names: Cossart, Pascale, editor. | Roy, Craig R., editor. | Sansonetti, P. J., editor.
Title: Bacteria and intracellularity / editors, Pascale Cossart, Institut Pasteur, Paris, France, Craig R. Roy, Yale University School of Medicine, New Haven, Connecticut, Philippe Sansonetti, Institut Pasteur, Paris, France.
Description: Hoboken : Wiley; Washington DC: American Society for Microbiology [2020] | Includes bibliographical references and index. | Description based on print version record and CIP data provided by publisher; resource not viewed.
Identifiers: LCCN 2019040621 (print) | LCCN 2019040622 (ebook) | ISBN 9781683670261 (adobe pdf) | ISBN 9781683670254 (hardback) | ISBN 9781683670254 (hardback) | ISBN 9781683670261 (adobe pdf)
Subjects: LCSH: Bacteria–Physiology. | Cell interaction.
Classification: LCC QR96.5 (ebook) | LCC QR96.5 .B325 2020 (print) | DDC 571.6/38293–dc23
LC record available at https://lccn.loc.gov/2019040621

Cover: Recapitulating the developing peripheral nervous system in a dish for studying Mycobacterium leprae interaction with Schwann cells in an in vivo-like microenvironment. Outgrowth of axons and migrating Schwann cells from embryonic mouse dorsal root ganglion. E14 mouse DRG neurites were labeled with neurofilament antibody (green) and Schwann cell nuclei were labeled with Hoechst dye (blue). Image taken on a Zeiss LSM 710 confocal microscope with 20 × objective. Courtesy of Samuel Hess and Anura Rambukkana.

Cover design by Debra Naylor, Naylor Design, Inc.

Contributors

Carmen Aguilar
Host RNA Metabolism Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany

Laurence Arbibe
INSERM U1151, CNRS UMR 8253, Institut Necker Enfants Malades, INEM Institute Department of Immunology, Infectiology and Hematology, Paris, France

Stephen Baker
Department of Medicine, University of Cambridge, Cambridge, United Kingdom, and Oxford University Clinical Research Unit (OUCRU), The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Josefin Bartholdson Scott
Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge, United Kingdom

Petr Broz
Department of Biochemistry, University of Lausanne, Switzerland

Dirk Bumann
Focal Area Infection Biology, Biozentrum, University of Basel, Basel, Switzerland

Rosalyn Casey
Department of Microbial Sciences, School of Biosciences and Medicine, University of Surrey, Guilford, Surrey, United Kingdom

Jean Celli
Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington

Simon Clare
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom

Michael Connor
Institut Pasteur, G5 Chromatine et Infection, Paris, France

Pascale Cossart
Institut Pasteur, Unité des Interactions Bactéries-Cellules (UIBC); Institut National de la Santé et de la Recherche Médicale (INSERM), U604; and Institut National de la Recherche Agronomique (INRA), USC2020, Paris, France

James P. di Santo
Innate Immunity Unit, Immunology Department, Institut Pasteur, and INSERM U1223, Paris, France

Gordon Dougan
Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom

Guillaume Duménil
Pathogenesis of Vascular Infections, Institut Pasteur, INSERM, Paris, France

Jost Enninga
Institut Pasteur, Dynamics of Host-Pathogen Interactions Unit, Cell Biology and Infection Department, Paris, France

Ana Eulalio
Host RNA Metabolism Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany, and RNA & Infection Group, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal

Alyssa C. Fasciano
Department of Molecular Biology and Microbiology and Program in Immunology, Sackler School of Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts

Celia W. Goulding
Department of Molecular Biology & Biochemistry and Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California

Christine Hale
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom

Melanie Hamon
Institut Pasteur, G5 Chromatine et Infection, Paris, France

Wolf-Dietrich Hardt
Institute of Microbiology, D-BIOL ETH Zurich, Zurich, Switzerland

Annika Hausmann
Institute of Microbiology, D-BIOL ETH Zurich, Zurich, Switzerland

Samuel Hess
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom

Suzie Hingley-Wilson
Department of Microbial Sciences, School of Biosciences and Medicine, University of Surrey, Guilford, Surrey, United Kingdom

Lu Huang
Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York

Scott J. Hultgren
Department of Molecular Microbiology and Center for Women’s Infectious Disease Research (CWIDR), Washington University School of Medicine, St. Louis, Missouri

Ralph R. Isberg
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts

William R. Jacobs, Jr.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York

Jonathan C. Kagan
Harvard Medical School and Division of Gastroenterology, Boston Children’s Hospital, Boston, Massachusetts

Frédéric Landmann
CRBM, University of Montpellier, CNRS, Montpellier, France

Yan Li
Innate Immunity Unit, Immunology Department, Institut Pasteur, and INSERM U1223, Paris, France

Miguel Mano
Functional Genomics and RNA-based Therapeutics Group, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal

Joan Mecsas
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts

Keira Melican
Swedish Medical Nanoscience Center, Karolinska Institutet, Stockholm, Sweden

Thomas F. Meyer
Max Planck Institute for Infection Biology, Department of Molecular Biology, Berlin, Germany

Evgeniya V. Nazarova
Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York

Dorian Obino
Pathogenesis of Vascular Infections, Institut Pasteur, INSERM, Paris, France

Charlotte Odendall
Kings College, Department of Infectious Diseases, Guy’s Hospital, London, United Kingdom

Natalie S. Omattage
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri

Titilayo O. Omotade
Department of Microbial Pathogenesis, Yale University, New Haven, Connecticut

Kim Orth
Department of Molecular Biology, Department of Biochemistry, and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas

Sophie Palmer
Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge, United Kingdom

Anura Rambukkana
MRC Centre for Regenerative Medicine and Centre for Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh, United Kingdom

Agneta Richter-Dahlfors
Swedish Medical Nanoscience Center, Karolinska Institutet, Stockholm, Sweden

Marion Rother
Steinbeis Innovation, Berlin-Falkensee; Institute of Experimental Internal Medicine, Otto von Guericke University Magdeburg, Magdeburg; and Max Planck Institute for Infection Biology, Berlin, Germany

Craig R. Roy
Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut

Thomas Rudel
Department of Microbiology, Biocenter, University of Wuerzburg, Wuerzburg, Germany

David G. Russell
Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York

Philippe J. Sansonetti
Institut Pasteur, Unité de Pathogénie Microbienne Moléculaire, INSERM U1202, and College de France, Paris, France

Marcela de Souza Santos
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas

Pamela Schnupf
Institut Imagine, Laboratory of Intestinal Immunity, INSERM UMR1163; Institut Necker Enfants Malade, Laboratory of Host-Microbiota Interaction, INSERM U1151; and Université Paris Descartes-Sorbonne, Paris, France

Caitlin N. Spaulding
Harvard University, School of Public Health, Boston, Massachusetts

Anna Spier
Institut Pasteur, UIBC; INSERM, U604; INRA, USC2020; and Bio Sorbonne Paris Cité, Université Paris Diderot, Paris, France

Fabrizia Stavru
Institut Pasteur, UIBC; INSERM, U604; INRA, USC2020; and CNRS, SNC 5101, Paris, France

Virginie Stévenin
Institut Pasteur, Dynamics of Host-Pathogen Interactions Unit, Cell Biology and Infection Department, Paris, France

Agathe Subtil
Institut Pasteur, Cell Biology of Microbial Infection, Paris, France

Kevin O. Tamadonfar
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri

Ana Rita Teixeira da Costa
Max Planck Institute for Infection Biology, Department of Molecular Biology, Berlin, Germany

Sangeeta Tiwari
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York

Sébastien Triboulet
Institut Pasteur, Cell Biology of Microbial Infection, Paris, France

Amy Yeung
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom

Rike Zietlow
Max Planck Institute for Infection Biology, Department of Molecular Biology, Berlin, Germany

Preface

We wish to dedicate this book to Stanley Falkow, who has impressed and influenced so many of us. Dr. Falkow launched the molecular study of host-bacterial pathogen interactions in the late 1970s, capitalizing on his knowledge of plasmids, antibiotic resistance, and molecular biology, before including cell biology, anticipating what came to be called cellular microbiology. Since then, nearly four decades of intense work on a variety of pathogens has highlighted common concepts in intracellularity but also very diverse mechanisms underlying the various infections produced by bacteria.

In launching this book, we wanted to cover many aspects and mechanisms of cellular microbiology, but more importantly, we intended to show that cellular microbiology as a field has reached maturity, extending beyond the strictly cellular level to infections of various organs and tissues. Many model organisms (Yersinia, Salmonella, Shigella, and Listeria, among others) are foodborne pathogens, and tremendous progress has been achieved in deciphering how, when, and where bacteria interact with the gut. However, intestinal cells and the intestine are not the only cells and organs discussed in this book. There are also chapters on infections of the urogenital tract, the endothelial barriers, the nervous system, and the lungs. Progress in the latter two concern important public health infections produced by Mycobacterium leprae and Mycobacterium tuberculosis. These two bacteria, which were at first much more difficult to manipulate than Escherichia coli, are now genetically tractable, and their study can now benefit from all the techniques and approaches established with less fastidious bacteria.

To be complete, a book on intracellularity had to include subcellular microbiology, and several chapters cover a variety of topics including metabolism of infected cells, nuclear biology, and microRNAs in host-pathogen interactions. All facets of cellular physiology are targeted by pathogens, and their role in infection is now actively assessed.

A book dedicated to “bacterial intracellularity” had to also include endosymbionts and, in particular, Wolbachia and its intriguing biology, which influences the capacity of the insects (in particular, mosquitoes) that carry this organism to transmit important viral pathogens such as dengue, Zika, and chikungunya viruses. This chapter is particularly timely, as a large official release of mosquitoes carrying Wolbachia has just been completed in New Caledonia to limit virus transmission by decreasing the global competence of this vector system.

The cellular microbiology field started in the late 1980s with a particular focus on cytoskeletal structures and organelles targeted by intracellular pathogens, but studies rapidly spread to analyze the cell autonomous defense pathways. We are happy to have two important chapters reviewing a field of research that has led to many new concepts in immunology and, more specifically, in innate immunity.

Finally, techniques and technologies are constantly improving: four chapters dealing with imaging, “omics” systems biology, and mouse humanization highlight the rapid progress in developing techniques that are now or will soon be used in the next steps of the study of intracellularity.

We thank the many colleagues who agreed to write for us. We are particularly happy to have gathered so many great chapters written by internationally recognized experts. We are well aware that studying pathogens without taking into account the microorganisms and microbial assemblies that are present in their vicinity may appear somewhat reductionist. This was a considered decision, and we believe a discussion of bacterial pathogenesis in the framework of microbiotas and microbiomes should be the topic of another book.

We thank Ellie Tupper and Richard Sever for their enthusiasm and patience during what at some stages seemed an endless project!

Pascale Cossart
Craig R. Roy
Philippe Sansonetti

About the Editors

Pascale Cossart earned her masters degree at Georgetown University, Washington, DC. She then received her Ph.D. in Paris at the Institut Pasteur, where she now leads the Bacteria-Cell Interactions unit. After early studies in DNA-protein interactions, in 1986 she began investigating the molecular and cellular basis of infections by intracellular bacteria, taking as a model the bacterium Listeria monocytogenes. Her research has led to new concepts in infection biology as well as in cell biology and fundamental microbiology, including RNA-mediated regulation. Dr. Cossart is considered a pioneer in cellular microbiology. Her contributions have been recognized by several international awards and election to several academies including the National Academy of Sciences (2009) and the National Academy of Medicine (2014). In January 2016, she was named Secrétaire Perpétuel de l’Académie des Sciences, Paris.

Craig R. Roy trained in the laboratory of Stanley Falkow at Stanford University, where his Ph.D. dissertation focused on the molecular mechanisms governing virulence in Bordetella pertussis. As a postdoctoral fellow in the laboratory of Ralph Isberg at Tufts University, he used cell biology to investigate Legionella pneumophila infection of macrophages. After a stint as assistant professor of Microbiology and Molecular Genetics at Stony Brook University, Dr. Roy helped found the new Department of Microbial Pathogenesis at Yale University in 1998. He is currently Waldemar Von Zedtwitz Professor of Microbial Pathogenesis and Immunobiology. Using multidisciplinary approaches, his laboratory has elucidated the mechanisms employed by intracellular pathogens to modulate vesicular transport and the host immune response against pathogens that reside in specialized organelles.

Philippe Sansonetti is professor and head of the Unité de Pathogénie Microbienne Moléculaire at the Pasteur Institute of Paris and chair of Microbiology and Infectious Diseases at the Collège de France. Professor Sansonetti qualified in medicine at the University of Paris in 1979. Following clinical work in France, he established his research career at Institut Pasteur in cellular microbiology and the pathogenesis of enteric infections, particularly Shigella, including vaccine development, and more recently the molecular cross-talks between microbiota and the gut epithelium. He is the recipient of numerous honors and awards including the Louis Jeantet Prize and a Howard Hughes Medical Institute Scholarship. He was awarded two successive ERC grants. He is currently Chief Editor of EMBO Molecular Medicine and a member of the French Academy of Science, the National Academy of Sciences (U.S.), and the Royal Society (UK).

Bacteria and Intracellularity

Contributors

Preface

About the Editors

I
Cellular Microbiology in the Study of Tissue and Organ Infections