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Rapporteurs: David A. Relman, Margaret A. Hamburg,
Eileen R. Choffnes, and Alison Mack
Forum on Microbial Threats
Board on Global Health
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and Food and Drug Administration; U.S. Department of Defense, Department of the Army:
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the Staatliche Museen in Berlin.
COVER: E. coli is a gram-negative, facultatively anaerobic, rod prokaryote. The strains are
undergoing conjugation via a pilus (one strain has fimbriae) under ×3,645 magnification.
Bacterial conjugation is the ability to transfer DNA between strains of bacteria (via a pilus).
It allows a new mutation to spread through an existing population. It is believed that this
process led to the spread of toxin synthesis from Shigella to E. coli (O157:H7). E. coli can
cause urinary tract infections, traveler’s diarrhea, nosocomial infections, meningitis, peri-
tonitis, mastitis, septicemia, and gram-negative pneumonia. It causes a variety of skin and
wound infections such as scalded skin syndrome, scarlet fever, erysipelas, and impetigo.
SOURCE: Cover art was provided by Dennis Kunkel Microscopy, Inc. The photo of
Joshua Lederberg on the spine is courtesy of The Rockefeller University.
Suggested citation: IOM (Institute of Medicine). 2009. Microbial evolution and co-
adaptation: a tribute to the life and scientific legacies of Joshua Lederberg. Washington,
DC: The National Academies Press.
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“Knowing is not enough; we must apply.
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— Goethe
Advising the Nation. Improving Health.
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FORUM ON MICROBIAL THREATS
DAVID A. RELMAN (Chair), Stanford University, Palo Alto, California
MARGARET A. HAMBURG (Vice Chair), Nuclear Threat Initiative/Global
Health & Security Initiative, Washington, DC
DAVID W. K. ACHESON, Center for Food Safety and Applied Nutrition, Food
and Drug Administration, Rockville, Maryland
RUTH L. BERKELMAN, Emory University, Center for Public Health
Preparedness and Research, Rollins School of Public Health, Atlanta, Georgia
ENRIQUETA C. BOND, Burroughs Wellcome Fund, Research Triangle Park,
North Carolina
ROGER G. BREEZE, Centaur Science Group, Washington, DC
STEVEN J. BRICKNER, Pfizer Global Research and Development, Pfizer Inc.,
Groton, Connecticut
GAIL H. CASSELL, Eli Lilly & Company, Indianapolis, Indiana
BILL COLSTON, Lawrence Livermore National Laboratory, Livermore,
California
RALPH L. ERICKSON, Global Emerging Infections Surveillance and
Response System, Department of Defense, Silver Spring, Maryland
MARK B. FEINBERG, Merck Vaccine Division, Merck & Co., West Point,
Pennsylvania
J. PATRICK FITCH, National Biodefense Analysis and Countermeasures
Center, Frederick, Maryland
DARRELL R. GALLOWAY, Medical S&T Division, Defense Threat
Reduction Agency, Fort Belvoir, Virginia
S. ELIZABETH GEORGE, Biological and Chemical Countermeasures
Program, Department of Homeland Security, Washington, DC
JESSE L. GOODMAN, Center for Biologics Evaluation and Research, Food
and Drug Administration, Rockville, Maryland
EDUARDO GOTUZZO, Instituto de Medicina Tropical–Alexander von
Humbolt, Universidad Peruana Cayetano Heredia, Lima, Peru
JO HANDELSMAN, College of Agricultural and Life Sciences, University of
Wisconsin, Madison
CAROLE A. HEILMAN, Division of Microbiology and Infectious Diseases,
National Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, Maryland
DAVID L. HEYMANN, Polio Eradication, World Health Organization,
Geneva, Switzerland
PHIL HOSBACH, New Products and Immunization Policy, Sanofi Pasteur,
Swiftwater, Pennsylvania
IOM Forums and Roundtables do not issue, review, or approve individual documents. The responsibil-
ity for the published workshop summary rests with the workshop rapporteur(s) and the institution.
v
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JAMES M. HUGHES, Global Infectious Diseases Program, Emory
University, Atlanta, Georgia
STEPHEN A. JOHNSTON, Arizona BioDesign Institute, Arizona State
University, Tempe
GERALD T. KEUSCH, Boston University School of Medicine and Boston
University School of Public Health, Massachusetts
RIMA F. KHABBAZ, National Center for Preparedness, Detection, and Control
of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta,
Georgia
LONNIE J. KING, Center for Zoonotic, Vectorborne, and Enteric Diseases,
Centers for Disease Control and Prevention, Atlanta, Georgia
GEORGE W. KORCH, U.S. Army Medical Research Institute for Infectious
Diseases, Fort Detrick, Maryland
STANLEY M. LEMON, School of Medicine, University of Texas Medical
Branch, Galveston
EDWARD McSWEEGAN, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, Maryland
STEPHEN S. MORSE, Center for Public Health Preparedness, Columbia
University, New York
MICHAEL T. OSTERHOLM, Center for Infectious Disease Research and
Policy, School of Public Health, University of Minnesota, Minneapolis
GEORGE POSTE, Arizona BioDesign Institute, Arizona State University, Tempe
JOHN C. POTTAGE, JR., GlaxoSmithKline, Collegeville, Pennsylvania
GARY A. ROSELLE, Central Office, Veterans Health Administration,
Department of Veterans Affairs, Washington, DC
JANET SHOEMAKER, Office of Public Affairs, American Society for
Microbiology, Washington, DC
P. FREDERICK SPARLING, University of North Carolina, Chapel Hill
BRIAN J. STASKAWICZ, Department of Plant and Microbial Biology,
University of California, Berkeley
TERENCE TAYLOR, International Council for the Life Sciences,
Washington, DC
MURRAY TROSTLE, U.S. Agency for International Development,
Washington, DC
Staff
EILEEN CHOFFNES, Director
KATE SKOCZDOPOLE, Senior Program Associate
SARAH BRONKO, Research Associate
KENISHA PETERS, Senior Program Assistant
ALISON MACK, Science Writer
vi
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BOARD ON GLOBAL HEALTH
Margaret Hamburg (Chair), Consultant, Nuclear Threat Initiative,
Washington, DC
George Alleyne, Director Emeritus, Pan American Health Organization,
Washington, DC
Donald Berwick, Clinical Professor of Pediatrics and Health Care Policy,
Harvard Medical School, and President and Chief Executive Officer,
Institute of Healthcare Improvement, Boston, Massachusetts
Jo Ivey Boufford (IOM Foreign Secretary), President, New York Academy of
Medicine, New York
David R. Challoner, Vice President for Health Affairs, Emeritus, University of
Florida, Gainesville
Ciro de Quadros, Albert B. Sabin Vaccine Institute, Washington, DC
Sue Goldie, Associate Professor of Health Decision Science, Department
of Health Policy and Management, Center for Risk Analysis, Harvard
University School of Public Health, Boston, Massachusetts
Richard Guerrant, Thomas H. Hunter Professor of International Medicine
and Director, Center for Global Health, University of Virginia School of
Medicine, Charlottesville
Gerald T. Keusch, Assistant Provost for Global Health, Boston University
School of Medicine, and Associate Dean for Global Health, Boston
University School of Public Health, Massachusetts
Jeffrey Koplan, Vice President for Academic Health Affairs, Emory
University, Atlanta, Georgia
Sheila Leatherman, Research Professor, University of North Carolina School of
Public Health, Chapel Hill
Michael Merson, Director, Duke Global Health Institute, Duke University,
Durham, North Carolina
Mark L. Rosenberg, Executive Director, Task Force for Child Survival and
Development, Emory University, Decatur, Georgia
Philip Russell, Professor Emeritus, Bloomberg School of Public Health, Johns
Hopkins University, Baltimore, Maryland
Staff
Patrick Kelley, Director
Allison Brantley, Senior Program Assistant
IOM boards do not review or approve individual reports and are not asked to endorse conclusions
and recommendations. The responsibility for the content of the report rests with the authors and the
institution.
vii
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Reviewers
This report has been reviewed in draft form by individuals chosen for their
diverse perspectives and technical expertise, in accordance with procedures
approved by the National Research Council’s Report Review Committee. The
purpose of this independent review is to provide candid and critical comments
that will assist the institution in making its published report as sound as possible
and to ensure that the report meets institutional standards for objectivity, evi-
dence, and responsiveness to the study charge. The review comments and draft
manuscript remain confidential to protect the integrity of the deliberative process.
We wish to thank the following individuals for their review of this report:
Martin J. Blaser, New York University School of Medicine
Steven J. Brickner, Pfizer Global Research and Development, Pfizer, Inc.
James M. Hughes, Hubert Department of Global Health and Rollins
School of Public Health, Emory University
Although the reviewers listed above have provided many constructive com-
ments and suggestions, they were not asked to endorse the final draft of the report
before its release. The review of this report was overseen by Dr. Melvin Worth.
Appointed by the Institute of Medicine, he was responsible for making certain
that an independent examination of this report was carried out in accordance with
institutional procedures and that all review comments were carefully considered.
Responsibility for the final content of this report rests entirely with the authoring
committee and the institution.
ix
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Preface
The Forum on Emerging Infections was created by the Institute of Medicine
(IOM) in 1996 in response to a request from the Centers for Disease Control and
Prevention (CDC) and the National Institutes of Health (NIH). The purpose of
the Forum is to provide opportunities for leaders from government, academia,
and industry to meet and examine issues of shared concern regarding research,
prevention, detection, and management of emerging or reemerging infectious
diseases. In pursuing this task, the Forum provides a venue to foster the exchange
of information and ideas, identify areas in need of greater attention, clarify policy
issues by enhancing knowledge and identifying points of agreement, and inform
decision makers about science and policy issues. The Forum seeks to illuminate
issues rather than resolve them; for this reason, it does not provide advice or
recommendations on any specific policy initiative pending before any agency or
organization. Its value derives instead from the diversity of its membership and
from the contributions that individual members make throughout the activities
of the Forum. In September 2003, the Forum changed its name to the Forum on
Microbial Threats.
ABOUT THE WORKSHOP
To a great extent, the Forum on Microbial Threats (hereinafter, the Forum)
owes its very existence to the life and legacies of the late Dr. Joshua Lederberg.
Along with the late Robert Shope and Stanley C. Oaks, Jr., Lederberg orga-
nized and co-chaired the 1992 Institute of Medicine study, Emerging Infections:
Microbial Threats to Health in the United States. The Emerging Infections report
xi
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xii PREFACE
helped to define the factors and dynamic relationships that lead to the emergence
of infectious diseases. Its recommendations addressed both the recognition of
and interventions against emerging infections as well as identified major unmet
challenges in responding to infectious disease outbreaks and monitoring the
prevalence of endemic diseases. This report ultimately led to the Forum’s creation
in 1996. As the first chair of the Forum, 1996-2001, Lederberg was instrumen-
tal in establishing it as a venue for the discussion and scrutiny of critical and
sometimes contentiousscientific and policy issues of shared concern related to
research on and the prevention, detection, and management of infectious diseases
and dangerous pathogens.
Lederberg’s long shadow may readily be appreciated in the Forum’s 2005
workshop, Ending the War Metaphor: The Changing Agenda for Unraveling the
Host-Microbe Relationship. Its central theme was derived from a comprehen-
sive essay that he published several years earlier in Science entitled “Infectious
History.” Under the heading, “Evolving Metaphors of Infection: Teach War No
More,” Lederberg argued that “[w]e should think of each host and its parasites
as a superorganism with the respective genomes yoked into a chimera of sorts.”
Thus began a discussion that developed the concept of the microbiome—a term
Lederberg coined to denote the collective genome of an indigenous microbial
community—as a forefront of scientific inquiry.
Having reviewed the shortcomings and consequences of the war metaphor
of infection Lederberg suggested, in the same essay, a “paradigm shift” in the
way we collectively identify and think about the microbial world around us,
replacing notions of aggression and conflict with a more ecologically—and
evolutionarily—informed view of the dynamic relationships among and between
microbes, hosts, and their environments. This perspective recognized the par-
ticipation of every eukaryotic organism—moreover, every eukaryotic cell—in
partnerships with microbes and microbial communities, and acknowledged that
microbes and their hosts are ultimately dependent upon one another for survival.
It also encouraged the exploration and exploitation of these ecological relation-
ships in order to increase agricultural productivity and to improve animal, human,
and environmental health.
More than a century of research, sparked by the germ theory of disease,
underlies our current appreciation of microbe-host-environment interactions.
Our “war” on infectious microbes has restricted the spread of several pathogens
and drastically reduced the burden of human disease, but the tide of the human
conquest shows many signs of turning. Over the past 30 years, 37 new human
pathogens have been identified as disease threats, and an estimated 12 percent of
known human pathogens have been recognized as either emerging or reemerg-
ing.1 Due in large part to the HIV/AIDS pandemic, the number of deaths in the
1 Merell,
D. S., and S. Falkow. 2004. Frontal and stealth attack strategies in microbial pathogenesis.
Nature 430(6996):250-256.
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xiii
PREFACE
United States attributable to infection, having fallen steadily since the turn of
the century, began to increase in the early 1980s. Infectious diseases continue to
cause high morbidity and mortality throughout the world, particularly in develop-
ing countries. In 2001, infectious diseases accounted for an estimated 26 percent
of deaths worldwide.
Clearly, a reconsideration of our interactions with pathogenic microbes is
warranted, and it must be based on a better understanding of host-microbe rela-
tionships in general. Estimates indicate that 90 to 99 percent of the approximately
1014 cells that comprise a healthy human body belong to the complex microbiota
that share our space. Only a small fraction of the roughly several thousand bacte-
rial species that inhabit our bodies cause illness; very little is known about the
other nonpathogenic bacteria, or even about microbes that in most cases cause
chronic, subclinical disease in humans, and that only occasionally produce ill-
ness and death. Research into our own microbial ecology and that of our fellow
eukaryotes, including plants, appears certain to reveal new strategies for prevent-
ing and treating a broad spectrum of infectious disease.
Dr. Lederberg’s death on February 2, 2008, marked the departure of a central
figure of modern science. It is in his honor that the Forum convened this public
workshop on May 20 and 21, 2008, to examine Dr. Lederberg’s scientific and
policy contributions to the marketplace of ideas in the life sciences, medicine,
and public policy. The agenda for this workshop demonstrates the extent to
which conceptual and technological developments have, within a few short years,
advanced our collective understanding of microbial genetics, microbial communi-
ties, and microbe-host-environment interactions. Through invited presentations
and discussions, participants explored a range of topics related to microbial evo-
lution and co-adaptation, including methods for characterizing microbial diver-
sity; model systems for investigating the ecology of host-microbe interactions
and microbial communities at the molecular level; microbial evolution and the
emergence of virulence; the phenomenon of antibiotic resistance and opportuni-
ties for mitigating its public health impact; and an exploration of current trends
in infectious disease emergence as a means to anticipate the appearance of future
novel pathogens.
As Adel Mahmoud, first co-chair of the Forum observed, “Joshua believed
very strongly in the work of this Forum. He had great confidence in the ability of
scientists and researchers to continue to solve some of the riddles that still con-
front science in the fight against infectious diseases. By remembering him with
this tribute, we are also remembering the many things that his life and career can
teach all of us. I hope that every time we meet at this Forum, Joshua Lederberg
will be an inspiration and a reminder that our work can truly change the world,
just as his life and career certainly did.”
It is to Josh’s life and living legacies that we dedicate this volume.
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xiv PREFACE
ACKNOWLEDGMENTS
The Forum on Microbial Threats and the IOM wish to express their grati-
tude to the individuals and organizations who, through their participation in this
workshop, provided invaluable information and advice to the Forum. A full list
of presenters may be found in Appendix A.
The Forum is deeply indebted to the IOM staff who contributed during
the course of the workshop and the production of this workshop summary. On
behalf of the Forum, we gratefully acknowledge the efforts led by Dr. Eileen
Choffnes, director of the Forum; Kate Skoczdopole, senior program associate;
Sarah Bronko, research associate; and Kenisha Peters, senior program assistant,
for dedicating much effort and time to developing this workshop’s agenda and for
their thoughtful and insightful approach and skill in planning for the workshop
and in translating the workshop’s proceedings and discussion into this workshop
summary. We would also like to thank the following IOM staff and consultants
for their valuable contributions to this activity: Alison Mack, Bronwyn Schrecker
Jamrok, Jackie Turner, Michael Hayes, and Florence Poillon.
Finally, the Forum wishes to recognize the sponsors that supported this
activity: U.S. Department of Health and Human Services: National Institutes of
Health, National Institute of Allergy and Infectious Diseases, Centers for Disease
Control and Prevention, and Food and Drug Administration; U.S. Department of
Defense: Global Emerging Infections Surveillance and Response System, Walter
Reed Army Institute of Research, U.S. Army Medical and Materiel Command,
and the Defense Threat Reduction Agency; U.S. Department of Veterans Affairs;
U.S. Department of Homeland Security; U.S. Agency for International Develop-
ment; U.S. Department of Energy: Lawrence Livermore National Laboratory;
American Society for Microbiology; Sanofi Pasteur; Burroughs Wellcome Fund;
Pfizer; GlaxoSmithKline; Infectious Diseases Society of America; and the Merck
Company Foundation.
David A. Relman, Chair
Margaret A. Hamburg, Vice Chair
Forum on Microbial Threats
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Contents
Workshop Overview 1
Appendix WO-1
Infectious History, 53
Joshua Lederberg, Ph.D.
Workshop Overview References, 71
1 The Life and Legacies of Joshua Lederberg 76
Overview, 76
Reflections on the Career of Joshua Lederberg, 77
David A. Hamburg, M.D.
Joshua Lederberg Remembered, 80
Stephen S. Morse, Ph.D.
The Life and Impact of a Legend—Joshua Lederberg, 88
Adel Mahmoud, M.D., Ph.D.
References, 94
2 Microbial Ecology and Ecosystems 95
Overview, 95
War and Peace: Humans and Their Microbiome, 101
David A. Relman, M.D.
Deciphering the Complex Molecular Dialogue of Symbiosis:
Esperanto or Polyglot?, 110
Margaret McFall-Ngai, Ph.D.
References, 118
xv
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xvi CONTENTS
3 Pathogen Evolution 121
Overview, 121
Bacterial Pathogenicity: An Historical and Experimental
Perspective, 126
Stanley Falkow, Ph.D.
Evolution of Bacterial-Host Interactions: Virulence and the Immune
Overresponse, 137
Elisa Margolis and Bruce R. Levin, Ph.D.
References, 152
4 Antibiotic Resistance: Origins and Countermeasures 158
Overview, 158
Antibiotic Resistance and the Future of Antibiotics, 160
Julian Davies, Ph.D.
Microbial Drug Resistance: An Old Problem in Need of
New Solutions, 173
Stanley N. Cohen, M.D.
Expanding the Microbial Universe: Metagenomics and Microbial
Community Dynamics, 180
Jo Handelsman, Ph.D.
References, 188
5 Infectious Disease Emergence: Past, Present, and Future 193
Overview, 193
Emerging Infections: Condemned to Repeat?, 195
Stephen S. Morse, Ph.D.
Ecological Origins of Novel Human Pathogens, 208
Mark Woolhouse, Ph.D., and Eleanor Gaunt, B.Sc.
Genomic Evolvability and the Origin of Novelty: Studying the Past,
Interpreting the Present, and Predicting the Future, 230
Jonathan A. Eisen, Ph.D.
Can We Predict Future Trends in Disease Emergence?, 252
Peter Daszak, Ph.D.
References, 266
Appendixes
A Agenda 273
B Acronyms 277
C Glossary 280
D Forum Member Biographies 287
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Tables, Figures, and Boxes
TABLES
WO-1 An Infectious Disease Timeline, 58
3-1 Some Examples of Virulence Resulting from an Immune
Overresponse, 142
4-1 Reports on Antibiotic Resistance Genes Isolated from the
Environment, 163
4-2 Mechanisms of Resistance, 2008, 164
4-3 Phylogeny of Cultured and Uncultured Bacteria from Third Instar
Gypsy Moth Midguts Feeding on an Artificial Diet, 183
5-1 New Opportunities for Pathogens: Ecological Changes, 200
5-2 Numbers of Pathogen Species by Taxonomic Category, 212
5-3 Dates of First Reports of Human Infection with Novel Pathogen
Species, 213
5-4 List of Human Pathogens Which Have Successfully Crossed the
Species Barrier and Proved Capable of Epidemic Spread and, in
Some Cases, Endemic Persistence in Human Populations, 225
5-5 BLAST Search Results as They Were Seen in 1997 Using the
MutS-like Protein from Helicobacter pylori as a Query, 234
xvii
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xviii TABLES, FIGURES, AND BOXES
FIGURES
WO-1 Newly emerging, reemerging or resurging, and deliberately emerging
diseases, 12
WO-2 Temporal profiles of the most abundant level 3 taxonomic groups, 20
WO-3 Six genotypes of Leptospirillum group II bacteria were detected in
the Richmond Mine (Iron Mountain, CA), 24
WO-4 Virus-host associations in AMD biofilms, 25
WO-5 The symbiotic continuum, 26
WO-6 Symbiotic relationship between plants and bacteria, 27
WO-7 The “winnowing,” 29
WO-8 Comparison of pathogenesis of infection associated with Salmonella
typhimurium versus S. typhi (human restricted), 35
WO-9 The relationship between antibiotic resistance development
in Shigella dysentery isolates in Japan and the introduction of
antimicrobial therapy between 1950 and 1965, 38
WO-10 Deaths resulting from infectious diseases decreased markedly in the
United States during most of the twentieth century, 42
WO-11 Global examples of emerging and reemerging infectious diseases, 43
WO-12 The convergence model, 45
WO-13 While known human pathogens are dominated by bacterial species,
the vast majority of novel pathogen species are viruses, 47
WO-14 Global distribution of relative risk of an EID event, 50
WO-15 Longer life, 57
2-1 Domain Bacteria, 103
2-2 Bacterial diversity in human colonic tissue and stool, 104
2-3 Site-specific distributions of bacterial phyla in healthy humans, 105
2-4 Representations of bacterial diversity, 106
2-5 Individualized responses to the same antibiotic, 108
2-6 The squid-vibrio association, 114
2-7 The series of events that characterize the trajectory of the
symbiosis, 115
2-8 Some symbiosis characteristics shared among the mouse, zebrafish,
and squid, 116
2-9 The language of symbiosis, 117
3-1 Pathogenic bacteria interfere with or manipulate for their own benefit
the normal function(s) of the host cell, 128
3-2 Salmonella infection, 129
3-3 Microarray-based negative selection strategy, 130
3-4 Time-dependent selection of persistence genes, 131
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xix
TABLES, FIGURES, AND BOXES
3-5 Response to Salmonella infection, 133
3-6 Response to Salmonella infection in 129sv mice following
immunization, 134
3-7 The decline of many infectious diseases in industrialized countries
(A) has been accompanied by an increase in immune disorders (B),
United States, 1950 to 2000, 136
3-8 The artist’s conception of the infection process and the host’s
immune response and overresponse, 139
4-1 Major classes of antimicrobials and the year of their discovery, 161
4-2 Integron mechanism of gene capture, 165
4-3 Concentration dependence of transcription modulation by
antibiotics, 167
4-4 The road to anthrax toxicity, 176
4-5 Diagrammatic representation of the site of chromosomal insertion of
a lentiviral GSV, 177
4-6 Detection of quorum-sensing activity and signal exchange in the guts
of cabbage white butterfly larvae, 184
4-7 Mortality of cabbage white butterfly larvae fed P. aeruginosa strains
and the quorum-sensing analog indole inhibitor, 185
4-8 Gypsy moth larvae reared on antibiotics are not susceptible
to Bt, 186
4-9 Restoration of B. thuringiensis toxicity by an Enterobacter spp. after
elimination of the detectable gut flora and B. thuringiensis activity by
antibiotics, 187
5-1 Leading causes of death in young adults, United States,
1987-2005, 197
5-2 Global examples of emerging and reemerging infectious
diseases, 199
5-3 A deer mouse (Peromyscus maniculatus), natural host for the Sin
Nombre (Hantavirus pulmonary syndrome) virus, with her
young, 202
5-4 Hantaviruses of the Americas, 203
5-5 Influenza pandemic 1918 at Camp Funston, Kansas, 205
5-6 World map indicating points of origin of the first reported
human cases of disease caused by 51 novel pathogen species
since 1980, 214
5-7 Counts of recently discovered human pathogens species associated
with various categories of non-human animal reservoirs, 217
5-8 The pathogen pyramid, 219
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xx TABLES, FIGURES, AND BOXES
5-9 Analysis of Andes virus outbreaks, 223
5-10 Phylogenetic prediction of gene function, 236
5-11 Phylogenetic tree of methyl-accepting chemotactic protein (MCP)
homologs in completed genomes, 240
5-12 Phylogenetic profile analysis of sporulation in Carboxydothermus
hydrogenoformans, 243
5-13 There is significant variation in the rate of evolution among
endosymbionts, with the highest rates tending to be found in those
that lack homologs of mismatch repair genes, 245
5-14 Phylogenetic trees of putative proteins encoded by single sequence
reads of DNA isolated from symbiont-containing tissue of the glassy-
winged sharpshooter, 249
5-15 The diversity of Bacterial and Archaeal species for which complete
genomes are available is still poor, 250
5-16 The rate of globalization has accelerated to the point where we
are connected as never before via globalized travel and trade
networks, 254
5-17 Economic impacts of selected emerging infectious diseases, 255
5-18 WNV is most likely to be spread by airplane, 256
5-19 Predicted risk of H5N1 avian influenza introduction from countries
that have had H5N1 outbreaks, 258
5-20 Species chain for Nipah virus in Malaysia, 260
5-21 Global richness map of the geographic origins of EID events from
1940 to 2004, 262
5-22 Global distribution of the relative risk of an EID event, 265
BOxES
WO-1 Joshua Lederberg: An Extraordinary Life, 4
WO-2 Host-Restriction Versus Virulence in Bordetella spp., 36
WO-3 Factors in Emergence, 44
WO-4 The Microbial World Wide Web, 69
1-1 Traits That Could Be the Foundation of Selection in Unfamiliar
Genomic Settings, 92
