This volume provides an overview of microbial toxins from diverse bacterial and fungal origins. These molecules, produced by various species and consisting of protein or small organic molecules, can play a pivotal role in pathogenesis of plants, animals, and humans that in turn can lead to the survival/dissemination of the host microbe. Many of these microbes, due to their toxins, impact our society from a health and economic perspective. In particular, this volume address the diverse niches of these organisms focused upon their associated toxins. The structures, functions, and genetics of toxins will be addressed. Besides the ill-effects elicited by these toxins, it must be noted that there is immense potential for turning some of these harmful molecules into useful tools as specific probes (of receptors), novel drugs or drug-conjugates for the treatment of various diseases, and immunomodulating agents for targeted vaccine delivery for research and unique medicines. Recent progress in bacterial genome mapping and establishment of three-dimensional crystal structures of several bacterial toxins provides a deeper knowledge and greater understanding of structure-function relationships. Moreover, the emergence of some bacteria (i.e., Bacillus anthracis, Burkholderia pseudomallei, Staphylococcus aureus), and their toxins, as biological weapons also necessitates a thorough understanding of these agents, their pathophysiology, and development of countermeasures. This volume will also be a common resource for researchers interested in many other medically-relevant microorganisms, and their toxins, that include Clostridium botulinum, C. difficile, C. perfringens, C. tetani, Escherichia coli, Helicobacter pylori, and Listeria monocytogenes. Recent studies have correlated the effect of global warming and climate change as a trigger for natural disasters and impact on human health via emergence of various vector-borne and infectious diseases caused by toxin-producing microbes. The 2003 Institute of Medicine (IOM) report, “Microbial Threats to Health,” identified the influence of changing ecosystem on the emergence and spread of infectious diseases and economic development of specific regions of the world. This current handbook is a major reference work on microbial toxins written by a panel of International experts and organized into 24 chapters. This handbook offers a comprehensive overview of toxinology. It covers all areas of toxinology, including topics like bioterrorism, toxin evolution and toxin based drug development.
Association Between Structure and Toxicity of Enterotoxigenic Escherichia coli (ETEC). – Heat-Stable Toxin Ib (STa). – Bacillus anthracis Toxins: Efficient Biochemical Weapons for the Infectious Battle. – Bacterial Genotoxins. – Bacterial Pore-Forming Toxin in Macromolecule Delivery: A Lesson Learned from Listeriolysin O. – Chaperones and ADP-ribosylating Bacterial Toxins. – Clostridium perfringens Epsilon Toxin. – Clostridium perfringens Iota Toxin: A Successfully-Shared Template for Common Enteric Pathogens. – Colibactin. – Cyanotoxins. – Escherichia coli Shiga Toxins. – Escherichia coli STb Toxin. – Food Poisoning in Bangladesh. – Glycosphingolipids as Toxin Receptors. Helicobacter pylori CagA: The Bacterial Oncoprotein. – Interaction of Helicobacter pylori VacA Toxin with Its Target Cells. – Membrane Degrading Toxins. – Mode of Action of Cry Toxins fromBacillus thuringiensis and Resistance Mechanisms. – Mycotoxin: Review and Detection. – Overview of Burkholderi pseudomallei Toxins and Clinical Implications. – Role of Bacterial Toxins in Enterotoxemia of Monogastrics and Ruminants. – Role of Clostridium difficileToxins in Antibiotic Associated Diarrhea and Pseudomembranous Colitis. – Role ofClostridium perfringens Toxins in Necrotic Enteritis in Poultry. – Role of Listeria Monocytogenes Toxins in Virulence. – RTX Toxins: A Review. – Structure Function Studies of Large Clostridial Cytotoxins. – Tetanus and Botulinum Neurotoxins. – Toxins ofStaphylococcus aureus: An Arsenal of Complementary Weapons. – Translocation of Toxins by Gram-Negative Pathogens Using the Type III Secretion System Prof. P. Gopalakrishnakone, M.B.B.S., Ph.D., F.A.M.S., D.Sc., is presently professor of anatomy and chairman of the Venom and Toxin Research Programme at Yong Loo Lin School of Medicine, National University of Singapore. He is also a consultant to the Defence Science Organization in Singapore and adjunct senior research scientist at the Defence Medical Research Institute. Prof. Gopalakrishnakone is an honorary principal fellow at the Australian Venom Research Unit, University of Melbourne, Australia. His research studies include structure function studies, toxin detection, biosensors, antitoxins and neutralization factors, toxicogenomics and expression studies, antimicrobial peptides from venoms and toxins, and PLA2 inhibitors as potential drug candidates for inflammatory diseases. The techniques he employs include quantum dots to toxinology, computational biology, microarrays, and protein chips. Prof. Gopalakrishnakone has more than 160 international publications, four books, about 350 conference presentations, and 10 patent applications. He has been an active member of the International Society on Toxinology (IST) for 30 years and was president from 2008 to 2012. He is also the founder president of its Asia Pacific Section, a council member, as well as an editorial board member of Toxicon, the society’s official journal. His research awards include the Outstanding University Researcher Award from the National University of Singapore (1998); Ministerial Citation, NSTB Year 2000 Award in Singapore; and the Research Excellence Award from the Faculty of Medicine at NUS (2003). His awards in teaching include Faculty Teaching Excellence Award 2003/4 and NUS Teaching Excellence Award 2003/4. Prof. Gopalakrishnakone also received the Annual Teaching Excellence Award in 2010 at both university and faculty levels.
for diverse topics in biology. His education in science was formally forged at Pennsylvania State University, Virginia Tech, and then the University of Texas. He spent over two decades in a Department of Defense laboratory studying protein toxins from snakes, marine cone snails, and bacteria. The goals were to further a basic understanding of how toxins affect cells, and subsequently generate methods for detection as well as neutralization via vaccines, therapeutic antibodies, and small molecular-weight inhibitors. Results from his laboratory led to numerous peer-reviewed publications with various national and international laboratories. National and international students have studied in his laboratory, and now further the tradition of understanding science. Besides working in the United States, he has formally studied in France and Germany at various universities and public/private laboratories. Dr. Stiles now teaches microbiology and basic biology courses at Wilson College, as well as Shippensburg University, both in the US.
Alberto Alape-Girón is a professor at the Department of Biochemistry, Faculty of Medicine, University of Costa Rica and head of Instituto Clodomiro Picado, also at University of Costa Rica. Prof. Alape-Girón received his Ph.D. from the Karolinska Institute in Stockholm, Sweden, and participates as a lecturer in biochemistry undergraduate and graduate courses at the University of Costa Rica. His research interests include bacterial and snake venom toxic proteins. Prof. Alape-Girón is associate editor of FEBS Open Bio and serves as a reviewer for several journals including mBio, BBA, PLOS One, Vaccine and Toxicon.
Dr. J. Daniel Dubreuil received a B.Sc. (Agr.) from Macdonald College (McGill University), a master’s degree from l’Université de Montréal and a Ph.D. (Department of Microbiology and
Immun
ology, Université de Montréal) executed at the Armand-Frappier Institute. A year postgraduate study was conducted at the Pasteur Institute in Paris, France (Unité des agents antibactériens), and two in the Department of Biochemistry and Microbiology (Victoria University, British Columbia, Canada). He joined the Faculty of Veterinary Medicine of the Université de Montréal in 1988.He was awarded the title of full professor in 1998. In 2001–2002, he was visiting scholar at the Instituto di Ricerche in Immunobiologiche Siena-Chiron, a pharmaceutical research center in Siena, Italy. There he conducted research on the virulence of Helicobacter pylori. He is the author of over 120 scientific publications, including many reviews and several book chapters on Escherichia coli toxins. Very involved with the Canadian Society of Microbiologists, he was elected president (2013–2014). Since June 2014, he is chair of the Department of Pathology and Microbiology, Faculty of Veterinary Medicine, Université de Montréal.
Dr. Manas Mandal received both bachelor’s (honours) and master’s degrees in human phyiology from the University of Calcutta, India. He earned a Ph.D. degree from the Jadavpur University, Calcutta, in 1992, working on snake venom vaccine development project at the Calcutta School of Tropical Medicine and Indian Institute of Chemical Biology. Afterwards, he did extensive post-doctoral research in cellular immunology at the Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, and University of Michigan College of Pharmacy. At the University of Michigan, he research centered on Listeria monocytogenes-derived toxin listeriolysin-O in a liposomal delivery system targeting antigen-specific protective cytotoxic T lymphocyte response using murine tumor and viral infection models. Dr. Mandal joined Roseman University of Health Sciences College of Pharmacy in 20
06 as a
n assistant p
rofessor to direct and coordinate immunology course for the Pharm.D. students. He also teaches immunology to the students of Roseman University College of Dental Medicine. Dr. Mandal is an adjunct faculty position at the Touro University of Nevada and teaches in their Physician’s Assistant Program and Doctor of Osteopathic Medicine program. He has published in major journals in toxinology, immunology and drug delivery. His current research interest involves use of bacterial toxin in vaccine delivery, marine toxin in drug discovery and drug-induced immune modulation.
Complete and comprehensive overview of toxinology
Written by renowned experts from all around the world
Covers all important areas of toxinology
