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Humans coexist with millions of harmless microorganisms, but emerging diseases, resistance to antibiotics, and the threat of bioterrorism are forcing scientists to look for new ways to confront the microbes that do pose a danger. This report identifies innovative approaches to the development of antimicrobial drugs and vaccines based on a greater understanding of how the human immune system interacts with both good and bad microbes. The report concludes that the development of a single superdrug to fight all infectious agents is unrealistic.
Throughout the biological world, bacteria thrive predominantly in surface-attached, matrix-enclosed, multicellular communities or biofilms, as opposed to isolated planktonic cells. This choice of lifestyle is not trivial, as it involves major shifts in the use of genetic information and cellular energy, and has profound consequences for bacterial physiology and survival. Growth within a biofilm can thwart immune function and antibiotic therapy and thereby complicate the treatment of infectious diseases, especially chronic and foreign device-associated infections. Modern studies of many important biofilms have advanced well beyond the descriptive stage, and have begun to provide molecular details of the structural, biochemical, and genetic processes that drive biofilm formation and its dispersion. There is much diversity in the details of biofilm development among various species, but there are also commonalities. In most species, environmental and nutritional conditions greatly influence biofilm development. Similar kinds of adhesive molecules often promote biofilm formation in diverse species. Signaling and regulatory processes that drive biofilm development are often conserved, especially among related bacteria. Knowledge of such processes holds great promise for efforts to control biofilm growth and combat biofilm-associated infections. This volume focuses on the biology of biofilms that affect human disease, although it is by no means comprehensive. It opens with chapters that provide the reader with current perspectives on biofilm development, physiology, environmental, and regulatory effects, the role of quorum sensing, and resistance/phenotypic persistence to antimicrobial agents during biofilm growth.
Technological Challenges in Antibiotic Discovery and Development is the summary of a workshop convened by the Chemical Sciences Roundtable in September 2013 to explore the current state of antibiotic discovery and examine the technology available to facilitate development. Through formal presentations and panel discussions, participants from academia, industry, federal research agencies discussed the technical challenges present and the incentives and disincentives industry faces in antibiotic development, and identified novel approaches to antibiotic discovery. Antibiotic resistance is a serious and growing problem in modern medicine and it is emerging as a pre-eminent public health threat. Each year in the United States alone, at least two million acquire serious infections with bacteria that are resistant to one or more antibiotics, and at least 23,000 people die annually as a direct result of these antibiotic-resistant infections. In addition to the toll on human life, antibiotic-resistant infections add considerable and avoidable costs to the already overburdened U.S. health care system. This report explores the challenges in overcoming antibiotic resistance, screening for new antibiotics, and delivering them to the sites of infection in the body. The report also discusses a path forward to develop the next generation of potent antimicrobial compounds capable of once again tilting the battle against microbial pathogens in favor of humans. Technological Challenges in Antibiotic Discovery and Development gives a broad view of the landscape of antibiotic development and the technological challenges and barriers to be overcome.
Antibiotics represent one of the most successful forms of therapy in medicine. But the efficiency of antibiotics is compromised by the growing number of antibiotic-resistant pathogens. Antibiotic resistance, which is implicated in elevated morbidity and mortality rates as well as in the increased treatment costs, is considered to be one of the major global public health threats (www.who.int/drugresistance/en/) and the magnitude of the problem recently prompted a number of international and national bodies to take actions to protect the public (http://ec.europa.eu/dgs/health_consumer/docs/road-map-amr_en.pdf: http://www.who.int/drugresistance/amr_global_action_plan/en/; http://www.whitehouse.gov/sites/default/files/docs/carb_national_strategy.pdf). Understanding the mechanisms by which bacteria successfully defend themselves against the antibiotic assault represent the main theme of this eBook published as a Research Topic in Frontiers in Microbiology, section of Antimicrobials, Resistance, and Chemotherapy. The articles in the eBook update the reader on various aspects and mechanisms of antibiotic resistance. A better understanding of these mechanisms should facilitate the development of means to potentiate the efficacy and increase the lifespan of antibiotics while minimizing the emergence of antibiotic resistance among pathogens.
This volume presents a comprehensive collection of methods that have been instrumental to the current understanding of bacterial persisters. Chapters in the book cover topics ranging from general methods for measuring persister levels in Escherichia coli cultures, protocols for the determination of the persister subpopulation in Candida albicans, quantitative measurements of Type I and Type II persisters using ScanLag, to in vitro and in vivo models for the study of the intracellular activity of antibiotics. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Bacterial Persistence: Methods and Protocols brings together the most respected researchers in bacterial persistence whose studies will remain vital to understanding this field for many years to come.
This book examines specific techniques which can be used to explore new drug targets and the effectiveness of new antibiotics. By testing new antimicrobial agents and modified existing drugs, the most vulnerable cell processes, such as cell wall and membrane synthesis, DNA replication, RNA transcription and protein synthesis, can be better exploited. This in-depth volume, however, delves even deeper by identifying additional novel cellular targets for these new therapies. The book will provide laboratory investigators with the vital tools they need to test the antimicrobial potential of products and to curb the rise of so many infectious diseases.
This volume covers all aspects of the antibiotic discovery and development process through Phase II/III. The contributors, a group of highly experienced individuals in both academics and industry, include chapters on the need for new antibiotic compounds, strategies for screening for new antibiotics, sources of novel synthetic and natural antibiotics, discovery phases of lead development and optimization, and candidate compound nominations into development. Beyond discovery , the handbook will cover all of the studies to prepare for IND submission: Phase I (safety and dose ranging), progression to Phase II (efficacy), and Phase III (capturing desired initial indications). This book walks the reader through all aspects of the process, which has never been done before in a single reference. With the rise of antibiotic resistance and the increasing view that a crisis may be looming in infectious diseases, there are strong signs of renewed emphasis in antibiotic research. The purpose of the handbook is to offer a detailed overview of all aspects of the problem posed by antibiotic discovery and development.
Focusing on phytochemicals and their potential for drug discovery, this book offers a comprehensive resource on poisonous plants and their applications in chemistry and in pharmacology. Provides a comprehensive resource on phytotoxins, covering historical perspectives, modern applications, and their potential in drug discovery Covers the mechanisms, benefits, risks and management protocols of phytotoxins in a scientific laboratory and the usefulness in drug discovery Presents chapters in a carefully designed, clear order, making it an ideal resource for the academic researcher or the industry professional at any stage in their career
Antibacterial agents act against bacterial infection either by killing the bacterium or by arresting its growth. They do this by targeting bacterial DNA and its associated processes, attacking bacterial metabolic processes including protein synthesis, or interfering with bacterial cell wall synthesis and function. Antibacterial Agents is an essential guide to this important class of chemotherapeutic drugs. Compounds are organised according to their target, which helps the reader understand the mechanism of action of these drugs and how resistance can arise. The book uses an integrated “lab-to-clinic” approach which covers drug discovery, source or synthesis, mode of action, mechanisms of resistance, clinical aspects (including links to current guidelines, significant drug interactions, cautions and contraindications), prodrugs and future improvements. Agents covered include: agents targeting DNA - quinolone, rifamycin, and nitroimidazole antibacterial agents agents targeting metabolic processes - sulfonamide antibacterial agents and trimethoprim agents targeting protein synthesis - aminoglycoside, macrolide and tetracycline antibiotics, chloramphenicol, and oxazolidinones agents targeting cell wall synthesis - β-Lactam and glycopeptide antibiotics, cycloserine, isonaizid, and daptomycin Antibacterial Agents will find a place on the bookshelves of students of pharmacy, pharmacology, pharmaceutical sciences, drug design/discovery, and medicinal chemistry, and as a bench reference for pharmacists and pharmaceutical researchers in academia and industry.