Strategies of Bacterial Interaction with Eukaryotic Cells *Tobias A. Oelschlaeger and Jorg Hacker 1. BENEFICIAL BACTERIAL-HOST INTERACTIONS Already during birth and soon thereafter mammals are colonized by bacte- ria belonging to the resident microbial flora. Cutaneous and mucosal sur- faces and the gastrointestinal tract are the areas which become colonized. These indigenous or autochthonous bacteria have a variety of beneficial effects on their hosts. They play a protective role by bacterial antagonism in fighting infections (Hoszowski and Truszczynski, 1997; Hentges, 1979). Pro- duction of vitamin K is another essential contribution of the resident microbial flora to the health of the host (Hill, 1997). Even more important, studies with germ-free animals demonstrated the involvement of the microbial flora on the development of the immune system. Such animals have underdeveloped and relatively undifferentiated lymphoid tissues and low concentrations of serum immune globulins ( Cebra et at., 1998). They TOBIAS A. OELSCHLAEGER and JORG HACKER Institut filr Molekulare lnfektionsbiologie, Universitiit Wiirzburg, 97070 Wiirzburg, Germany. *Corresponding author; Phone: (0)931-312150; FAX: (0)931-312578; E-mail: [email protected] xxix Tobias A. Oelschlaeger and Jorg Hacker also show defects in specific immune responsiveness and in nonspecific resistance induced by endotoxin, which may account for their lowered resis- tance. A more typical example of symbiotic interaction of bacteria with a host are bacteria like Ruminococcus in the gut of ruminants, essential for degradation of cellulose (Hobson, 1988). The closest benefical bacterial-host interactions are those of intracellular symbiotic bacteria and their host cells.

This book examines the current state of probiotic research and in particular focuses on the future potential of this important and exciting area. Probiotics and Prebiotics contains state-of-the-art commentaries on all aspects of the intestinal microflora and probiotics and provides an authoritative review of important aspects of probiotic research. Written by leading experts in the field, each chapter affords a critical insight to a particular topic, reviews current research, discusses future direction and stimulates discussion. Topics covered include the genomics of probiotic microorganisms, the developing technologies for analysis of gut microorganisms, evaluation and future potential of prebiotic substances, and the potential for disease prevention in the host by probiotic organisms. This book is an essential text for all microbiologists, health professionals, biotechnologists, pharmaceutical companies, and dairy and food scientists.

This book provides a comprehensive and detailed source of information on the genetic and regulatory aspects of biological nitrogen fixation in free-living (non-symbiotic) prokaryotes. Biological nitrogen fixation is represented in a diverse range of microorganisms, among which Klebsiella pneumoniae serves as a paradigm for the genetic analysis of diazotrophy, which is the ability to grow with N2 as sole nitrogen source. The volume uses two major complementary approaches to the subject matter. The initial chapters use an organismic-based approach by concentrating on the well-characterized diazotrophic proteobacteria, cyanobacteria, Gram-positive clostridia, and Archea. The later chapters use a comparative process-based approach and serve as overviews dealing with different regulatory aspects, electron transport to nitrogenase, and molybdenum metabolism, across the range of organisms. Whenever appropriate, historical aspects and agricultural and ecological impacts have been taken into consideration. Each chapter contains an extensive list of references. This book is the self-contained second volume of a comprehensive seven-volume series. No other available work provides the up-to-date and in-depth coverage of this series and this volume. This book is intended to serve as an indispensable reference work for all scientists working in this and closely related fields, to assist students to enter this challenging area of research, and to provide science administrators easy access to vital relevant information.

In biological terms, a parasite can be defined as a oean organism that grows, feeds and is sheltered on, or in, a different organism while contributing nothing to the survival of the host.a 1 This relationship is particularly intimate for parasitic protozoa (and single-celled fungi such as the Microsporidia), many of which not only penetrate tissue barriers, but gain entry into host cells. The entry mechanisms are as diverse as the organisms employing them and are often critical components of their pathogenic profile. All of the parasitic organisms highlighted in this new book represent medically important human pathogens that contribute significantly to the global burden of disease. As such there is intense interest in understanding the molecular basis of infection by these pathogensa "not only with regard to their clinical relevance but also the fascinating biology they reveal. For most of the parasites discussed here (Plasmodium falciparum, Toxoplasma gondii, Cryptosporidium parvum, Trypanosoma cruzi and Leishmania spp.) the ability to penetrate biological barriers and/or to establish intracellular residence is critical to survival of the pathogen in the mammalian hosts. For other parasites, such as Entamoeba, a tissue invasive phenotype is a key virulence determinant. In the ensuing 18 chapters, select members of this diverse set of protozoan parasites, as well as some examples of the extremely reduced fungal parasites classified as Microsporidia, are discussed within the context of the fascinating molecular strategies employed by these organisms to migrate across biological barriers and to establish residence within target host cells.

In this timely book, leading international Pasteurellaceae scientists critically review the most important current research providing an up-to-date review of the molecular biology, genomics and virulence of these fascinating organisms. Topics covered include taxonomy and biodiversity, phylogeny, comparative genomics, competence, DNA uptake and transformation, proteomics and protein secretion, RTX toxins, lipopolysaccharides, biofilms, quorum sensing, antimicrobial resistance, diagnosis, and OMP and iron uptake. Each chapter is independent and can be read in isolation and as a whole the book provides an important resource summarising our current knowledge of Pasteurellaceae genomics and molecular biology. Essential reading for everyone working on Pasteurellaceae and related organisms.

This volume covers the fields of origin, evolution and phylogenesis from prokaryotic to eukaryotic cells. The eminent authors, experts in their fields, review the three kingdoms of life (Archea, Eubacteria and Eukarya) from molecular evolutionary levels to ecological aspects in enigmatic habitats, including general reviews of puzzling pro-and eukaryotic organisms and their domains. We discuss dry habitats, thermophilic (cells in hot springs and undersea thermal vents up to 110AC), psychrophilic (cryophiles) and halophilic (high salt concentrations) niches which among the harshest conditions found on Earth where microbial life is frequently detected. Some chapters deal with the organisms which grow in extreme pH conditions (acidity vs. alkalinity), and under hydrostatic pressure in the deep sea, and microbial growth on petroleum. Other contributors present their research on aerobiology and microbes growing in various gases and various levels of radiation, including cellular morphological modification in these extremophilic microbes. This volume also includes the symbiotic association between two or more organisms on the endocellular and exocellular levels. Finally one paper identifies the extremophiles as candidates for exobiology. This is a valuable comprehensive volume in English that covers most of the extremophiles in a new light with current research data. Audience: Students, lecturers and researchers; scholars in the fields of biology, evolutionary biology and chemistry, and other evolutionary fields, and the intelligent layman.

The future of agriculture strongly depends on our ability to enhance productivity without sacrificing long-term production potential. An ecologically and economically sustainable strategy is the application of microorganisms, such as the diverse bacterial species of plant growth promoting bacteria (PGPB). The use of these bio-resources for the enhancement of crop productivity is gaining worldwide importance.

"Bacteria in Agrobiology: Crop Ecosystems" describes the beneficial role of plant growth promoting bacteria with special emphasis on oil yielding crops, cereals, fruits and vegetables. Chapters present studies on various aspects of bacteria-plant interactions, soil-borne and seed-borne diseases associated with food crops such as rice, sesame, peanuts, and horticultural crops. Further reviews describe technologies to produce inoculants, the biocontrol of post harvest pathogens as a suitable alternative to agrochemicals, and the restoration of degraded soils.

Biological nitrogen fixation (BNF) has become important in rice farming systems because this process diminishes the need for expensive chemical fertilizers which have been associated with numerous health and environmental problems. The extensive exploitation of BNF would provide economic benefits to small farmers, avoiding all malign influences of chemical fertilizers. Meanwhile, advances in biotechnology have brought rice genetics to the threshold of new opportunities for increasing rice production. This volume focuses, in six different sessions, on the role of BNF in the improvement of rice production in the light of the current state of the art of BNF technology transfer and diffusion. New ideas on BNF technology in research, extension information and inoculant technology are also included, together with the socio-economic impacts of using BNF in rice farm systems.

The functional analysis of plant-microbe interactions has re-emerged in the past 10 years due to spectacular advances in integrative study models. This book summarizes basic and technical information related to the plant growth promoting rhizobacteria (PGPR) belonging to the genus Azospirillum, considered to be one of the most representative PGPR last 40 years. We include exhaustive information about the general microbiology of genus Azospirillum, their identification strategies; the evaluation of plant growth promoting mechanisms, inoculants technology and agronomic use of these bacteria and some special references to the genetic technology and use.

Plant conservation is increasingly recognised as an outstanding global priority, yet despite considerable efforts over the last few decades, the number of threatened species continues to rise. The practice of plant conservation has for too long been a rather hit-or-miss mixture of methods. While microorganisms have been recognised as a crucial and essential element in supporting the lifecycles of plant species, there has been limited recognition of the relationships between macro level conservation facilitating ecosystem functioning at the micro level.

This book addresses the role of microorganisms in conservation - both their support functions and deleterious roles in ecosystem processes and species survival. Importantly, a number of authors highlight how microbial diversity is, itself, now under threat from the many and pervasive influences of man. What is clear from this volume is that like many contemporary treatments of plant and animal conservation, the solution to mitigate the erosion of biodiversity is not simple. This book represents an attempt to bring to the fore the ecological underwriting provided by microorganisms.

The ancient beverage wine is the result of the fermentation of grape must. This n- urally and fairly stable product has been and is being used by many human societies as a common or enjoyable beverage, as an important means to improve the quality of drinking water in historical times, as therapeutical agent, and as a religious symbol. During the last centuries, wine has become an object of scientific interest. In this respect different periods may be observed. At first, simple observations were recorded, and subsequently, the chemical basis and the involvement of microorg- isms were elucidated. At a later stage, the scientific work led to the analysis of the many minor and trace compounds in wine, the detection and understanding of the biochemical reactions and processes, the diversity of microorganisms involved, and the range of their various activities. In recent years, the focus shifted to the genetic basis of the microorganisms and the molecular aspects of the cells, including metabolism, membrane transport, and regulation. These different stages of wine research were determined by the scientific methods that were known and available at the respective time. The recent "molecular" approach is based on the analysis of the genetic code and has led to significant results that were not even imaginable a few decades ago. This new wealth of information is being presented in the Biology of Microorganisms on Grapes, in Must, and in Wine.

Researchers in the field of ecological genomics aim to determine how a genome or a population of genomes interacts with its environment across ecological and evolutionary timescales. Ecological genomics is trans-disciplinary by nature. Ecologists have turned to genomics to be able to elucidate the mechanistic bases of the biodiversity their research tries to understand. Genomicists have turned to ecology in order to better explain the functional cellular and molecular variation they observed in their model organisms.

We provide an advanced-level book that covers this recent research and proposes future development for this field. A synthesis of the field of ecological genomics emerges from this volume."Ecological Genomics"covers a wide array of organisms (microbes, plants and animals) in order to be able to identify central concepts that motivate and derive from recent investigations in different branches of the tree of life.

"Ecological Genomics"covers 3 fields of research that have most benefited from the recent technological and conceptual developments in the field of ecological genomics: the study of life-history evolution and its impact of genome architectures; the study of the genomic bases of phenotypic plasticity and the study of the genomic bases of adaptation and speciation.

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Our world is built on an invisible one we are barely beginning to understand. In The Hidden Half of Nature, geologist David R. Montgomery and biologist Anne Bikle argue that Earth's smallest creatures-microbes-could fundamentally change how we grow food, what we eat and how we practise medicine. The Hidden Half of Nature shares Montgomery and Bikle's efforts to turn a barren patch of ground into a flourishing garden, and Bikle's struggle with cancer. Taking readers deep into the science and history of agriculture and immunology, they show that microbes can provide powerful solutions to the problems plaguing modern agriculture as well as our own bodies. A spellbinding story, The Hidden Half of Nature reveals how we can restore fertility to the land and defeat chronic diseases.

It has been known for a number of years that not only pathogenicity islands but also plasmids and bacteriophages are able to carry genes whose products are involved in pathogenic processes. Accordingly, such elements and their products play an important role in pathogenesis due to the intestinal E. coli as well due to Shigellae. Another interesting aspect which is reflected in different articles is that genomes evolve by acquisition of new pieces of DNA following gene transfer, but also by genome reduction. Different mechanisms include the deletion of sequences or the elimination of functions by the accumulation of point mutations or rearrangements.

Although virology and immunology are now considered separate disciplines, history shows that these areas ofinvestigation always overlapped and one cannot really exist without the other. This trend has become particularly significant and fruitful in the past few years in the area of herpesvirus research. The genomes of the most important herpesviruses have been sequenced, a significant portion of their genes have been identified, and many secrets of regulation of gene expr- sion have been unraveled. Now this progress sets the stage for a true revolution in herpesvirus research: analysis of interactions between the host and the virus. Because herpesviruses can induce, suppress, and fool the immune system, the most productive herpesvirologists are also expert immunologists, and the current results ofthis interdisciplinary effort are truly remarkable. Because herpesviruses cause many important human diseases, the devel- ment of vaccines against these agents is a very significant goal. This effort is also very challenging because of the complexity of herpesviruses and the lack of sufficient information about immune responses. The remarkable ability of herpesviruses to escape immune responses is - other feature that brings immunology and virology together. Herpesviruses - code many proteins that interact with and down-regulate some key elements of the immune system. Thisproperty of herpesviruses represents amajor challenge in developing strategies against these viruses. On the positive side, these viral proteins also provide novel tools for analyzing specific immune reactions and molecular mechanisms.

Cyanobacteria are single-celled organisms that live in fresh, brackish, and marine water. They use sunlight to make their own food. In warm, nutrient-rich environments, microscopic cyanobacteria can grow quickly, creating blooms that spread across the water 's surface and may become visible. Because of the color, texture, and location of these blooms, the common name for cyanobacteria is blue-green algae. However, cyanobacteria are related more closely to bacteria than to algae. Cyanobacteria are found worldwide, from Brazil to China, Australia to the United States. In warmer climates, these organisms can grow year-round. Scientists have called cyanobacteria the origin of plants, and have credited cyanobacteria with providing nitrogen fertilizer for rice and beans. But blooms of cyanobacteria are not always helpful. When these blooms become harmful to the environment, animals, and humans, scientists call them cyanobacterial harmful algal blooms (CyanoHABs). Freshwater CyanoHABs can use up the oxygen and block the sunlight that other organisms need to live. They also can produce powerful toxins that affect the brain and liver of animals and humans. Because of concerns about CyanoHABs, which can grow in drinking water and recreational water, the U.S. Environmental Protection Agency (EPA) has added cyanobacteria to its Drinking Water Contaminant Candidate List. This list identifies organisms and toxins that EPA considers to be priorities for investigation. Reports of poisonings associated with CyanoHABs date back to the late 1800s. Anecdotal evidence and data from laboratory animal research suggest that cyanobacterial toxins can cause a range of adverse humanhealth effects, yet few studies have explored the links between CyanoHABs and human health. Humans can be exposed to cyanobacterial toxins by drinking water that contains the toxins, swimming in water that contains high concentrations of cyanobacterial cells, or breathing air that contains cyanobacterial cells or toxins (while watering a lawn with contaminated water, for example). Health effects associated with exposure to high concentrations of cyanobacterial toxins include: stomach and intestinal illness; trouble breathing; allergic responses; skin irritation; liver damage; and neurotoxic reactions, such as tingling fingers and toes. Scientists are exploring the human health effects associated with long-term exposure to low levels of cyanobacterial toxins. Some studies have suggested that such exposure could be associated with chronic illnesses, such as liver cancer and digestive-system cancer. This monograph contains the proceedings of the International Symposium on Cyanobacterial Harmful Algal Blooms held in Research Triangle Park, NC, September 6-10, 2005. The symposium was held to help meet the mandates of the Harmful Algal Bloom and Hypoxia Research and Control Act, as reauthorized and expanded in December 2004. The monograph will be presented to Congress by an interagency task force. The monograph includes: 1) A synopsis which proposes a National Research Plan for Cyanobacteria and their Toxins; 2) Six workgroup reports that identify and prioritize research needs; 3) Twenty-five invited speaker papers thatdescribe the state of the science; 4) Forty poster abstracts that describe novel research.

The symposium, "Microbial Diversity in Time and Space," was held in the Sanjo Conference Hall, University of Tokyo, Tokyo, Japan, October 24-26, 1994. The symposium was organized under the auspices of the Japanese Society of Microbial Ecology and co-sponsored by the International Union of Biological Sciences (IUBS), International Union of Microbiological Societies (IUMS), International Committee on Microbial Ecology (ICOME), and the Japanese Society of Ecology. The aim of the symposium was to stress the importance of the global role of microorganisms in developing and maintaining biodiversity. Twenty-four speakers from seven countries presented papers in the symposium and in the workshop, "Microbial Diversity and Cycling of Bioelements," that followed the symposium. Papers presented at the symposium are published in this proceedings. Discussions of the workshop, which were energetic and enthusiastic, are also summarized in this proceedings. The symposium provided an opportunity to address the role of microorganisms in global cycles and as the basic support ofbiodiversity on the planet. Previously unrecognized as both contributing to and sustaining biodiversity, microorganisms are now considered to be primary elements of, and a driving force in, biodiversity. Financial support was provided for the symposium by the CIBA GEIGY Foundation for the Promotion of Science, Naito Foundation, and the Uchida Foundation of the Ocean Research Institute, University of Tokyo. Support from these foundations is gratefully acknowledged. CONTENTS Microbial Biodiversity-Global Aspects ................................. 1 Rita R. Colwell 2. Importance of Community Relationships in Biodiversity ...................

The tetracyclines have an illustrious history as therapeutic agents which dates back over half a century. Initially discovered as an antibiotic in 1947, the four ringed molecule has captured the fancy of chemists and biologists over the ensuing decades. Of further interest, as described in the chapter by George Armelagos, tetracyclines were already part of earlier cultures, 1500-1700 years ago, as revealed in traces of drug found in Sudanese Nubian mummies. The diversity of chapters which this book presents to the reader should illus trate the many disciplines which have examined and seen benefits from these fascinating natural molecules. From antibacterial to anti-inflammatory to anti autoimmunity to gene regulation, tetracyclines have been modified and redesigned for various novel properties. Some have called this molecule a biol ogist's dream because of its versatility, but others have seen it as a chemist's nightmare because of the synthetic chemistry challenges and "chameleon-like" properties (see the chapter by S. Schneider).

The use of renewable bioenergy is increasing, and so is the production of associated wastes: biomass ashes. This book presents eleven chapters on the options for recycling such biomass ashes, ranging from their use as fertilizer in agriculture and forestry to their application as a supplement for the production of cement-based materials or bricks. The book also examines the pros and cons for each of the different uses of biomass ashes.

In the post genomic era, understanding of the innate immune system is enriched by findings on the specificity of innate immune reactions as well as to novel functions that do not strictly correlate with immunological defense and surveillance, immune modulation or inflammation. This volume covers natural killer cells, mast cells, phagocytes, toll-like receptors, complement, host defense in plants and invertebrates, evasion strategies of microorganisms, pathophysiology, protein structures, design of therapeutics, and experimental approaches.

Magnetoreception or magnetotaxis in bacteria was discovered only some 30 years ago. All magnetotactic bacteria, which occur in many environments and display a remarkable diversity, synthesize magnetosomes, complex intracellular organelles that contain magnetic iron crystals.

Recent developments in the research on magnetotactic bacteria are presented in this volume. Included are reviews on the formation and organization of magnetosomes, the genes controlling magnetosome biomineralization, and new cryogenic techniques to visualize novel cytoskeleton structures. Described here are potential nanobiotechnological applications of the magnetosome crystals, which have magnetic and crystalline characteristics unmatched by their inorganic counterparts. Related topics such as the impact of biogenic magnetic crystals in geobiology and paleomagnetism also are discussed. The aim of the book is to provide a broad survey of this multidisciplinary field and to inspire future research on these fascinating organisms.

Cold-adapted microorganisms play a major role in nutrient turnover and primary biomass production in cold ecosystems and have important applications in biotechnology and in the study of food spoilage microorganisms. Divided into three main sections, the book covers the major aspects of biodiversity in cold ecosystems, the physiology and molecular adaptation mechanisms, and the various biomolecules related to cold adaptation.

This Volume provides protocols for the biochemical analysis of hydrocarbon- and lipid-relevant products, cell components and activities of microbes that interact with hydrophobic compounds. They include methods for the extraction, purification and characterisation of surface tension-reducing bioemulsifiers and biosurfactants that increase the surface area and hence bioavailability of hydrophobic substrates. Protocols for the isolation and biochemical analysis of lipids and polyhydroxyalkanoates, food storage products made during nutrient abundance that represent important biotechnological products, are presented. The extraction of membrane lipid rafts, sub-organelles that fulfil important functional roles for the cell membrane, and the isolation and characterisation of membrane phospholipid biomarkers, are also described. The purification and characterisation of integral membrane hydrocarbon-oxidising enzymes are addressed. Lastly, two generic methods for the genetic analysis of catabolic pathways and analysis of ligand binding are presented. Hydrocarbon and Lipid Microbiology ProtocolsThere are tens of thousands of structurally different hydrocarbons, hydrocarbon derivatives and lipids, and a wide array of these molecules are required for cells to function. The global hydrocarbon cycle, which is largely driven by microorganisms, has a major impact on our environment and climate. Microbes are responsible for cleaning up the environmental pollution caused by the exploitation of hydrocarbon reservoirs and will also be pivotal in reducing our reliance on fossil fuels by providing biofuels, plastics and industrial chemicals. Gaining an understanding of the relevant functions of the wide range of microbes that produce, consume and modify hydrocarbons and related compounds will be key to responding to these challenges. This comprehensive collection of current and emerging protocols will facilitate acquisition of this understanding and exploitation of useful activities of such microbes.