TREATING INFECTIOUS DISEASES IN A MICROBIAL WORLD
Report of Two Workshops on Novel Antimicrobial Therapeutics
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NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This study was supported by Contract No. N01-OD-4-2139 (Task Order #153) between the National Academy of Sciences and the National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government.
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Cover image: Confocal micrograph depicting a common behavior of bacteria (green) gathering in mucus shed by host epithelial cells (red). Such behavior has been noted in both beneficial and pathogenic associations with microbial partners. This image shows the gathering of the microbial symbiont Vibrio fischeri during its colonization of tissues of the host squid Euprymna scolopes. As described in the report, models such as the squid-vibrio system promise to provide insight into the mechanisms underlying the reciprocal dialogue between the hosts and their microbial partners, whether the relationship results in health or disease. Image courtesy of Laura Sycuro and Margaret McFall-Ngai.
Copyright 2006 by the National Academy of Sciences. All rights reserved.
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COMMITTEE ON NEW DIRECTIONS IN THE STUDY OF ANTIMICROBIAL THERAPEUTICS: NEW CLASSES OF ANTIMICROBIALS
CHRISTOPHER T. WALSH (Chair),
Harvard Medical School, Boston, Massachusetts
BONNIE L. BASSLER,
Princeton University, Princeton, New Jersey
CARL F. NATHAN,
Weill Medical College of Cornell University, New York, New York
THOMAS F. O’BRIEN,
Brigham and Women’s Hospital, Boston, Massachusetts
MARGARET RILEY,
University of Massachusetts, Amherst, Massachusetts
RICHARD J. WHITE,
Vicuron Pharmaceuticals, Fremont, California
GERARD D. WRIGHT,
McMaster University, Hamilton, Ontario, Canada
Staff
ADAM P. FAGEN, Study Director
ANN H. REID, Program Officer
ROBERT T. YUAN, Senior Program Officer
JOSEPH C. LARSEN, Postdoctoral Research Associate
MATTHEW D. McDONOUGH, Program Assistant (through August 2005)
ANNE F. JURKOWSKI, Program Assistant (since September 2005)
NORMAN GROSSBLATT, Senior Editor
COMMITTEE ON NEW DIRECTIONS IN THE STUDY OF ANTIMICROBIAL THERAPEUTICS: IMMUNOMODULATION
ARTURO CASADEVALL (Chair),
Albert Einstein College of Medicine, New York, New York
RITA R. COLWELL,
University of Maryland, College Park, Maryland; Johns Hopkins University, Baltimore, Maryland; and Canon U.S. Life Sciences, Arlington, Virginia
R.E.W. (BOB) HANCOCK,
University of British Columbia, Vancouver, British Columbia, Canada
MARGARET JEAN McFALL-NGAI,
University of Wisconsin, Madison, Wisconsin
CARL F. NATHAN,
Weill Medical College of Cornell University, New York, New York
LIISE-ANNE PIROFSKI,
Albert Einstein College of Medicine, New York, New York
ARTHUR TZIANABOS,
Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts
DENNIS M. ZALLER,
Merck Research Laboratories, Rahway, New Jersey
Staff
ANN H. REID, Study Director
ADAM P. FAGEN, Program Officer
ROBERT T. YUAN, Senior Program Officer
JOSEPH C. LARSEN, Postdoctoral Research Associate
MATTHEW D. McDONOUGH, Program Assistant (through August 2005)
ANNE F. JURKOWSKI, Program Assistant (since September 2005)
NORMAN GROSSBLATT, Senior Editor
BOARD ON LIFE SCIENCES
COREY S. GOODMAN (Chair),
Renovis, Inc., South San Francisco, California
ANN M. ARVIN,
Stanford University School of Medicine, Stanford, California
JEFFREY L. BENNETZEN,
University of Georgia, Athens, Georgia
RUTH BERKELMAN,
Emory University, Atlanta, Georgia
DEBORAH BLUM,
University of Wisconsin, Madison, Wisconsin
R. ALTA CHARO,
University of Wisconsin, Madison, Wisconsin
DENNIS CHOI,
Merck Research Laboratories, West Point, Pennsylvania
JEFFREY L. DANGL,
University of North Carolina, Chapel Hill, North Carolina
PAUL R. EHRLICH,
Stanford University, Stanford, California
JAMES M. GENTILE,
Research Corporation, Tucson, Arizona
JO HANDELSMAN,
University of Wisconsin, Madison, Wisconsin
ED HARLOW,
Harvard Medical School, Boston, Massachusetts
DAVID HILLIS,
University of Texas, Austin, Texas
KENNETH H. KELLER,
University of Minnesota, Minneapolis, Minnesota
RANDALL MURCH,
Virginia Polytechnic Institute and State University, Alexandria, Virginia
GREGORY A. PETSKO,
Brandeis University, Waltham, Massachusetts
STUART L. PIMM,
Duke University, Durham, North Carolina
JAMES TIEDJE,
Michigan State University, East Lansing, Michigan
KEITH YAMAMOTO,
University of California, San Francisco, California
Staff
FRANCES E. SHARPLES, Director
KERRY A. BRENNER, Senior Program Officer
MARILEE K. SHELTON-DAVENPORT, Senior Program Officer
ROBERT T. YUAN, Senior Program Officer
ADAM P. FAGEN, Program Officer
ANN H. REID, Program Officer
EVONNE P. Y. TANG, Program Officer
DENISE GROSSHANS, Financial Associate
ANNE F. JURKOWSKI, Program Assistant
Acknowledgments
Each report benefited from the contribution of the speakers and participants in the respective workshops. The agenda, speakers, and participant list for each workshop are provided as an appendix to each report.
The immunomodulation committee would also like to acknowledge David Schneider, Stanford University, for preparing the figure highlighting the complexity of the immune system, and Fiona Roche, Simon Fraser University, for preparing the Cytoscape figure of the TLR4 pathway.
These reports have been reviewed in draft form by persons 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 the published reports as sound as possible and to ensure that the reports meet institutional standards of objectivity, evidence, 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 these reports:
Christine A. Biron, Brown University
Richard A. Flavell, Yale University
Emil C. Gotschlich, The Rockefeller University
Lora Hooper, University of Texas Southwestern Medical Center at Dallas
Harry F. Noller, University of California, Santa Cruz
John H. Rex, AstraZeneca Pharmaceuticals
Jerome S. Schultz, University of California, Riverside
Peter M. Small, Bill and Melinda Gates Foundation
Elaine Tuomanen, St. Jude Children’s Research Hospital
H. Boyd Woodruff, Soil Microbiology Associates
Although the reviewers listed above have provided constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final drafts of the reports before their release. The review of these reports was overseen by Elaine L. Larson, Columbia University, and Leslie Z. Benet, University of California, San Francisco. Appointed by the National Research Council, they were responsible for making certain that an independent examination of these reports was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of these reports rests entirely with the authoring committees and the institution.