Basic Research on Bacteria The Essential Frontier Report on the American Society for Microbiology and National Institutes of Health Workshop on Basic Bacterial Research The National Institutes of Health (NIH) The Nationʼs Medical Research Agency, the NIH includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov The American Society for Microbiology (ASM) The ASM is the largest single life science society, composed of over 42,000 scientists and health profes - sionals. The ASM's mission is to promote research and research training in the microbiological sciences and to assist communication between scientists, policy makers and the public to improve health, economic well-being and the environment. The ASM and its members work to identify and support research efforts that can address health and environmental problems. February 2007 Cover and Interior Bacteria Images Staphylococcus aureus —coccus prokaryote (MRSA bacterium) Mycobacterium tuberculosis —rod prokaryote (bacterium) E. coli Escherichia coli ( )—dividing, hemorrhagic 0157:H7 strain. © Dennis Kunkel Microscopy www.denniskunkel.com Introduction or many years the American Society for Microbiology (ASM) has been concerned about the need for increasing basic research in bacteriology. This concern is based upon several premises, including: F 1 the widespread perception that an adequate number of researchers in the U.S. in fields such as bacterial physiology and genetics are not being trained, 2 the importance of basic knowledge of bacterial physiology and genetics in the biotechnology industry and in applications including pathogenesis and biodefense, 3 the growing understanding of the impact of bacteria on human health, and on the development of chronic diseases. To address these questions, the ASM and National Institutes of Health (NIH) jointly sponsored a workshop on Basic Research in Bacteriology that was convened November 3-4, 2005 on the NIH campus in Bethesda, Maryland. Approach Goal: The workshop participants focused on the he ASM-NIH workshop focused on scientific gaps and opportunities for research on bacteria. In order to stim - following discussion areas: Tulate creative, goal-oriented interactions, the meeting inte - grated focused discussions within smaller working groups • What are the gaps in our knowledge, methodologies, and overarching sessions with entire group participation. and information access that must be addressed? Participants in the two-day workshop included scientists What strategies would address these gaps? with a variety of research expertise, representatives of industry, and representatives of federal agencies. Following • How has microbiological research at the basic and the meeting, the groupʼs Steering Committee prepared this applied levels been changed by technological advances summary of the discussions and recommendations to (e.g., genomics, imaging, and computation)? What new guide future research. opportunities have been revealed? • How have these technological advances altered the per - ception of what problems are interesting and important? What are the benefits and drawbacks to these changes? • What factors have changed the marketplace for microbiologists over the years and how? Is this picture changing again? What are the roles of the research insti - tutions in these shifts and how might they be influenced in the future? What are the roles of the microbiological societies in future shifts? What roles might the private and public funding agencies play? • What are the developments on the horizon that will affect microbiological research in the next five years? Basic Research on Bacteria The Essential Frontier 1 Overview Despite the broad impact of this field, basic research on bacteria is at a crossroads. The research community acteria and their phages are the oldest and most perceives that public funding for most areas of basic abundant life forms on the planet. Bacteria have research, including bacteriology, has leveled off and that Bco-evolved with us and are beneficial for human health. There increased resources are being focused on infectious disease are over 10 times more bacteria in our bodies than there research prompted in part by biodefense concerns. Coupled are human cells, and this natural microbiota is essential to this, large multi-investigator projects have emerged as an for proper development, nutrition, and resistance to disease. alternative to single investigator R01-type research projects. However, we also live in an environment replete with bacteria These developments raise the questions: What is the relative that can cause a wide variety of human diseases with value of continued investment in basic research on bacteria, bacterial infections responsible for 25 percent of human and is there a disproportionate emphasis on large scientific deaths globally, a number predicted to increase dramatically consortia at the expense of research by smaller groups? with the growing crisis of antibiotic resistance. We under - stand very little about the interactions between bacteria Evolving Priorities and the environment that influence the delicate ecological equilibrium between humans and microbes and thereby esearch on bacteria and their phages has led to many determine the balance between health and disease. fundamental scientific discoveries. Initial support for this Rresearch was justified in part because of the role of bacteria In addition to the bacteria that are in or on the human body, in causing disease. With the advent of effective antibiotics it bacteria influence humans in many other ways. Bacteria are seemed like the war on microbes had been won. Hence, for the dominant occupant and architect of our entire biosphere. several decades health-related research shifted to topics Bacteria sustain the metabolic cycles that are essential for all like cancer, heart disease, and genetic diseases. Moreover, life on earth. Bacterial metabolism sculpts our physical envi - developments in molecular biology arising from research on ronment as well. Because they are ubiquitous and have such bacteria made it possible to study many basic biological diverse metabolic capabilities, bacteria influence essentially processes in mammalian cells, eliminating the argument all disciplines of science, including fields such as evolutionary that bacterial model systems were the only doorway to biology, ecology, immunology, cell and developmental biolo - eukaryotic molecular biology. gy, psychology, geology, chemistry, physics, climatology, computer science, and engineering. Meanwhile, the microbes demonstrated how rapidly they could evolve new traits. Microbial resistance to antibiotics Bacteria are also instrumental for understanding funda - developed faster than new antibiotics could be developed, mental life processes that are required by all organisms, and the resistance spread throughout the microbial world. including central metabolism, replication, transcription, The global expansion of food distribution networks facilitated translation, protein targeting, assembly and structure the rapid distribution of microbial pathogens. Simultaneously, of macromolecular complexes, protein folding, stress emerging microbial pathogens filled new ecological niches, responses, error correction mechanisms, signal transduction, such as indwelling medical devices and the growing popula - and developmental programs. These processes are more tion of humans who are immunocompromised due to pri - easily characterized in model bacteria and their phages mary infections (including HIV) or due to therapies used to than in other organisms because microbes provide such treat chronic diseases. Furthermore, recent discoveries tractable experimental systems. The large repertoire of have demonstrated that some diseases (including ulcers, genetic and biochemical tools and data that have been certain types of cancer, heart disease, etc.) that were pre - acquired from basic research on bacteria is crucial for viously believed to be caused by a genetic predisposition dissecting the complex metabolic and regulatory networks or exposure to environmental toxins are actually caused by that control these processes. This provides a launching microbes. This microbial offensive has summoned a point for understanding the enormous diversity in the bacterial world and facilitates the understanding of these processes in eukaryotes. 2 renewed counter-attack on microbial pathogens. Impact of New Technologies Meanwhile, new tools have become available that make it possible to dissect the molecular basis of pathogenesis ew approaches like genomics, transcriptomics, and both from the microbial and host perspectives. Recently, proteomics allow the identification of the entire genetic having the complete DNA sequences of bacterial Ncomplement of bacteria and which of these genes are turned pathogens has provided valuable insights into how micro - on under particular conditions. Comparative genomics led to bial pathogens evolve and the extent of gene transfer the discovery that gene exchange between bacteria is ram - between pathogens. These advances have revealed new pant and has dramatically influenced the acquisition of viru - ways to control infection, including the