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Beschreibung

The study of Bacillus Anthracis remains at the forefront of microbiology research because of its potential use as a bioterror agent and its role in shaping our understanding of bacterial pathogenesis and innate immunity. Bacillus Anthracis and Anthrax provides a comprehensive guide to all aspects of the organism, ranging from basic biology to public health issues associated with anthrax. This book will be a premier reference for B. Anthracis and anthrax to microbiologists, medical and public health professionals, bioterror research and preparedness, immunologists, and physiologists.

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Table of Contents

Cover

Title page

Copyright page

Dedication

Preface

Contributors

Chapter 1 Anthrax from 5000 BC to AD 2010

FROM ANCIENT TIMES TO THE 19TH CENTURY

TWENTIETH-CENTURY ANTHRAX

Chapter 2 Outer Structures of the Bacillus anthracis Spore

SPORE ULTRASTRUCTURE

THE FUNCTIONS OF THE SPORE OUTER LAYERS

FUNCTIONS OF THE COAT

FUNCTIONS OF THE EXOSPORIUM

ASSEMBLY OF THE SPORE OUTER STRUCTURES

SUMMARY AND FUTURE DIRECTIONS

Chapter 3 Anthrax Spore Germination

INTRODUCTION

ANTHRAX AND THE SPORE

SPORE GERMINATION IN VIVO

SPORE GERMINATION IN VITRO

GERMINATION MACHINERY

Chapter 4 Genetic Manipulation Methods in Bacillus anthracis

INTRODUCTION

DELIVERY OF FOREIGN DNA

ISOLATION OF MUTANTS

CONCLUDING REMARKS

Chapter 5 The Bacillus anthracis Genome

INTRODUCTION

B. ANTHRACIS SEQUENCING PROJECTS

FEATURES OF THE B. ANTHRACIS GENOME

GENES ENCODED BY B. ANTHRACIS

POPULATION BIOLOGY

CONCLUSIONS: AN EXTRAORDINARY PATHOGEN WITH AN ORDINARY CHROMOSOME?

Chapter 6 Bacillus anthracis Plasmids: Species Definition or Niche Adaptation?

THE B. CEREUS GROUP

PLASMIDS OF B. ANTHRACIS

B. CEREUS GROUP PLASMIDS SIMILAR TO B. ANTHRACIS PLASMIDS

CONCLUSIONS

Chapter 7 Iron Acquisition by Bacillus anthracis

INTRODUCTION

HOST-IRON METABOLISM

IRON WITHIN MACROPHAGES

B. ANTHRACIS IRON ACQUISITION STRATEGIES

HEME TOXICITY

CONCLUSION

Chapter 8 Anthrax Toxins

BRIEF OVERVIEW OF ANTHRAX TOXIN RESEARCH

PA

LF

EF

FINAL REMARKS

Chapter 9 Bacillus anthracis Virulence Gene Regulation

INTRODUCTION

SIGNALS FOR VIRULENCE GENE EXPRESSION

ATXA: THE MAJOR REGULATOR OF THE VIRULENCE GENES

A CONVERGENCE OF COMPLEX REGULATORY SYSTEMS

DIFFERENTIAL GENE REGULATION IN THE B. CEREUS GROUP SPECIES AND PLASMID–CHROMOSOME CROSSTALK

REGULATION OF OTHER VIRULENCE-ASSOCIATED GENES

CONCLUSION

ACKNOWLEDGMENTS

Chapter 10 The Interactions between Bacillus anthracis and Macrophages

THE FACILITATION OF SPORE INFECTION BY MACROPHAGES: DEVELOPMENT OF A MODEL

THE ROLE OF MACROPHAGES IN INNATE HOST DEFENSES

THE METABOLIC CONSEQUENCES OF INFECTION FOR B. ANTHRACIS AND THEIR HOST MACROPHAGES

MACROPHAGES AS IN VITRO MODEL OF PATHOGENESIS AND IMMUNITY

Chapter 11 Bacillus anthracis and Dendritic Cells: A Complicated Battle

INTRODUCTION

DCS: SUBSET DIVERSITY, TOPOLOGY, AND FUNCTIONS

DCS AND B. ANTHRACIS: A COMPLICATED BATTLE

CONCLUDING REMARKS

Chapter 12 Bacillus anthracis Dissemination through Hosts

INTRODUCTION

ENTRY

INVASION

DISSEMINATION

CONCLUDING REMARKS

ACKNOWLEDGMENTS

Chapter 13 Pathology, Diagnosis, and Treatment of Anthrax in Humans

WHO ACTIVITIES ON ANTHRAX SURVEILLANCE AND CONTROL

DIAGNOSTIC CLINICAL CHARACTERISTICS OF PATIENTS WITH ANTHRAX

LABORATORY DIAGNOSIS OF ANTHRAX

PATHOLOGY OF ANTHRAX IN HUMAN CASES

TREATMENT OF ANTHRAX IN HUMAN PATIENTS

Chapter 14 Anthrax Vaccines

INTRODUCTION

DEVELOPMENT OF CELLULAR VACCINES

DEVELOPMENT OF ACELLULAR VACCINES

VACCINE EFFICACY

DURATION OF IMMUNITY

VACCINE SAFETY

RECOMBINANT PA VACCINES

ANTHRAX VACCINE RESEARCH

CONCLUSIONS AND FUTURE PROSPECTS

Chapter 15 Anthrax as a Weapon of War and Terrorism

THE POWER OF MICROBES

THE POISON TABOO

CHALLENGES TO THE NORM

THE BIOLOGICAL WEAPONS CONVENTION (BWC) AND SOVIET PERFIDY

MORE ANTHRAX WORRIES: AUM SHINRIKYO AND IRAQ

THE U.S. ANTHRAX ATTACKS

SEEKING THE PERPETRATOR

WORLD AT RISK

CONCLUSION

Index

Color Plates

Copyright © 2011 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New Jersey

Published simultaneously in Canada

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permissions.

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Library of Congress Cataloging-in-Publication Data:

Bacillus anthracis and anthrax / edited by: Nicholas H. Bergman.

p. cm.

 Includes index.

 ISBN 978-0-470-41011-0 (cloth)

 ISBN 978-1-118-14808-2 (epub)

 1. Anthrax. 2. Bacillus anthracis. I. Bergman, Nicholas H.

 QR201.A6B33 2011

 614.5′61–dc22

2010037931

This book is dedicated to the scientists throughout the world who have devoted their careers to studying Bacillus anthracis and other biothreat agents. Their commitment to understanding the biology of these organisms in the face of technical, financial, and political obstacles has given us the foundations of biodefense, and for this, society owes them its deep gratitude.

Preface

Looking back over the past decade, it is clear that our understanding of Bacillus anthracis and anthrax has improved dramatically in recent years. Much of this is due to technical advances that were beneficial to microbiology in a very broad sense. Genome sequencing, improved animal models, and efficient methods for genetic manipulation, for instance, have made it possible to address questions in microbiology that were inaccessible only a few years ago. In addition, the attention given to B. anthracis because of its potential as a bioterror weapon has brought both more funding and more researchers to the study of anthrax, and this has also played a big role in accelerating research in this field.

Although the rapid progress made in anthrax research over the past few years has certainly been welcomed by the research and public health communities, it has also meant that in many areas of B. anthracis biology and pathogenesis, our knowledge extends well beyond what is reported in previous reference volumes. In developing this book, my aim was to address this issue, and to bring together a collection of reviews that would provide scientists and health professionals with a current and comprehensive reference on both B. anthracis and anthrax.

I am extremely grateful to the authors who contributed to the book—they represent some of the most accomplished researchers in the anthrax field, and their expertise and effort is clear in the chapters they have written. I am also grateful to the editorial staff at John Wiley & Sons for their advice and support, and specifically to Karen Chambers for her help in the earliest stages of this book’s conception. Finally, I thank my friend and colleague Dr. Karla Passalacqua, for the many useful discussions as this book was being planned.

Contributors

Joel A. Bozue, Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases

Katherine A. Carr, Department of Microbiology and Immunology, University of Michigan Medical Center

Leonard A. Cole, Division of Global Affairs, Rutgers University, Center for Law and Justice

Christopher K. Cote, Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases

Carlos del Rio, Department of Pathology and Laboratory Medicine, Emory University School of Medicine

Adam Driks, Department of Microbiology and Immunology, Loyola University Medical Center

Nathan Fisher, United States Army Medical Research Institute of Infectious Diseases

Jonathan D. Giebel, Department of Microbiology and Immunology, University of Michigan Medical Center

Ian J. Glomski, Department of Microbiology, University of Virginia

Jeannette Guarner, Department of Pathology and Laboratory Medicine, Emory University School of Medicine

Philip C. Hanna, Department of Microbiology and Immunology, University of Michigan Medical Center

Brian K. Janes, Department of Microbiology and Immunology, University of Michigan Medical Center

Theresa M. Koehler, Department of Microbiology and Molecular Genetics, University of Texas—Houston Health Science Center

Stephen H. Leppla, Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Michael Mallozzi, Department of Microbiology and Immunology, Loyola University Medical Center

Mahtab Moayeri, Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Gleb Pishchany, Department of Microbiology and Immunology, Vanderbilt University Medical School

Anne Quesnel-Hellmann, Groupe interactions hôte-agent pathogène, Département de biologie des agents transmissibles, Centre de Recherches du Service de Santé des Armées

Conrad P. Quinn, National Center for Immunization and Respiratory Diseases, Division of Bacterial Diseases, Meningitis and Vaccine Preventable Diseases Branch, Microbial Pathogenesis and Immune Response Laboratory, Centers for Disease Control and Prevention

Jason M. Rall, Department of Microbiology and Molecular Genetics, University of Texas—Houston Health Science Center

David A. Rasko, Department of Microbiology and Immunology, University of Maryland School of Medicine, Institute for Genome Sciences

Timothy D. Read, Division of Infectious Diseases, Department of Human Genetics, Emory University School of Medicine

Elke Saile, National Center for Immunization and Respiratory Diseases, Division of Bacterial Diseases, Meningitis and Vaccine Preventable Diseases Branch, Microbial Pathogenesis and Immune Response Laboratory, Centers for Disease Control and Prevention

Sean V. Shadomy, Bacterial Zoonoses Branch, Centers for Disease Control

Eric P. Skaar, Department of Microbiology and Immunology, Vanderbilt University Medical School

Scott Stibitz, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research Food and Drug Administration

Jean-Nicolas Tournier, Groupe interactions hôte-agent pathogène, Département de biologie des agents transmissibles, Centre de Recherches du Service de Santé des Armées

Peter C.B. Turnbull, Salisbury, UK

Susan L. Welkos, Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases

Chapter 1

Anthrax from 5000 BC to AD 2010

Peter C. B. Turnbull and Sean V. Shadomy

FROM ANCIENT TIMES TO THE 19TH CENTURY

Historical Names of Anthrax

Anthrax (Latin, a carbuncle) is derived from the Greek (anthrax) meaning coal and referring to the characteristic black eschar in human cutaneous anthrax. Other older names for the disease, such as “malignant pustule” or “black bane,” and names in other languages, such as charbon (French) and carbonchio (Italian), similarly reflect these features. Yet other names reflect other manifestations of the disease in humans and/or animals or its sources of infection, such as woolsorter’s/ragpicker’s/Bradford disease and the German equivalent Hadernkrankheit (rag disease), splenic fever, Milzbrand (German, meaning “spleen fire”), Siberian plague, Lodiana fever, and Pali plague in India, and many more. The many names in many languages reflect the historical and widespread recognition of the numerous features of anthrax before it was understood that they were all manifestations of a single etiological agent.

The earliest application of the name “anthrax” to the afflictions caused by Bacillus anthracis is uncertain. “Bloody murrain” was probably the most common term for the disease in animals in early English language texts, and carbuncle—or malignant carbuncle to distinguish it from other carbuncular manifestations—was the term used for the cutaneous infection in humans. From a book of 1766, Viljoen (1928) cites “Visit to your servant girl suffering from a considerable anthrax and found several furuncles on the back; cured same” but believes that “anthrax” at that time was a common term embracing any severe localized dermatitis and this was not a B. anthracis infection. According to Swiderski (2004), physicians attending George Washington diagnosed as “an anthrax” “a very large and painful tumor” which developed on his left thigh about 6 weeks after his inauguration as first president of the United States in 1789. However, that description and the description of “anthrax, or carbuncle” in the American edition of The Surgeon’s Vade-Mecum (1813) similarly appear unlikely to have been B. anthracis infections.

Figure 1.1 From a culture of anthrax blood in chicken broth at 24–48 h.

(From Ch Chamberland’s celebrated book Charbon et Vaccination Charbonneuse d’après les travaux de Mr Pasteur, 1883.)

Figure 1.2 The same culture after several days, with spores now apparent.

(From Ch Chamberland’s celebrated book Charbon et Vaccination Charbonneuse d’après les travaux de Mr Pasteur, 1883.)

From Ancient Egypt to 1892

The allegedly long history of anthrax features in numerous papers and articles. Most scholarly among those readily accessible today are probably the papers of Klemm and Klemm (1959) and Blancou (2000) which, together, supply a brief but comprehensive review of earlier literature attesting to the historical familiarity with the disease through the ages. Klemm and Klemm (1959) suggest anthrax originated in early Egypt and Mesopotamia, where agriculture was established some 5000 years BC, and then address the feasibility of the frequently cited statement that the fifth plague of Egypt in the time of Moses (ca 1250 BC)—“a grievous murrain affecting cattle, horses, asses, camels, oxen and sheep”—was the earliest instance of systemic anthrax on record. As Ebedes (1981) points out, no other disease kills such a wide spectrum of species. Others also consider the sixth plague—boils breaking out in sores on man and beast—to have been cutaneous anthrax. Ebedes (1981) suggests these lesions affected only the Egyptians because only the Egyptians would have handled the carcasses of affected animals, the Israelites being forbidden to touch dead animals. Not everyone concurs with these hypotheses; Morens (2002), for example, considers the evidence that the fifth Pharaonic plague in the biblical book of Exodus was anthrax to be weak.

Klemm and Klemm (1959) and Blancou (2000) also summarize the evidence that early Greece was familiar with anthrax as depicted by Homer in his “Iliad” (ca 1230 BC), Hippocrates’ writings (ca 400 BC) and the plague of Athens in 430 BC (see also Morens and Littman, 1992), Aristotle in his History of Animals (ca 333 BC), Plutarch (ca AD 120), and Galen (ca AD 200); that it was described in Hindu literature of around 500 BC and that, based on the writings of Livius (ca 460 BC), Virgil (70 BC–90 BC), and Vegetius (ca AD 400), the Romans were well acquainted with it. Dirckx (1981) had no doubt that the Norican plague (now Bavaria) in Virgil’s third Georgic (ca 32 BC) was anthrax. Klemm and Klemm (1959) even suggest that anthrax may have contributed to events that led to the fall of Rome. According to Dong (1990), anthrax has featured in Chinese animal husbandry for millennia, being especially well described in the Jin and Sui dynasties (AD 500–600) by Ge Hong in his Handbook of Prescriptions and Ch’ao Yaun Fang in the General Treatise on the Etiology and Symptomatology of Diseases.

Klemm and Klemm (1959) believe that records of the occurrence of anthrax in post-Roman Europe begin with references to what is likely to have been this disease in the Hippiatrika (horse medicine), a tenth-century collection of veterinary writings, and the eleventh century The Medicine of Quadrupeds Blancou (2000) summarizes records of the death of a clan chief in Ireland in 1030 from what may well have been anthrax; of Arab authors in the twelfth and thirteenth centuries describing anthrax-like signs in cattle; the description in 1250 by German Emperor Frederick II’s chief veterinarian of what appears to have been anthrax in horses; a description by one Pietro di Crescenzi (Italy) of what is thought to have been anthrax in sheep in the late 1200s; and further descriptions of probable anthrax in animals and humans in 1316, 1523, 1673, and 1745. D. E. Salmon (after whom Salmonella species were named) informs us that “anthrax was frequently confounded with the rinderpest, but is described with sufficient precision to identify outbreaks of it in epizoötic form in 996 A.D. and 1090 in France; in 1552 at Lucca, Italy; in 1617 at Naples, where numbers of human beings died from eating the flesh of animals affected with the disease” (Salmon, 1896). He further documents references to the disease in animals in Venice in 1598, extensive outbreaks in Germany, Hungary, and Poland in 1709–1714, its extensive spread in the early 1800s in Russia, Holland, and England, and again in Russia during the mid-1800s when, in 1864, “more than 10,000 horses and nearly 1000 persons perished from the disease.” In Novogrod (Russia), between 1867 and 1870, 528 people and 56,000 cattle died of anthrax (Klemm and Klemm, 1959; Koch, 1877). Some 60,000 people were reported to have died in the 1617 Naples epidemic, and 15,000 people allegedly died from anthrax in San Domingo (now Haiti) within 6 weeks in 1770 (Higgins, 1916; Morens, 2002).

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