This book, written by leading international experts, provides a comprehensive, current examination of transport-mediated antimicrobial resistance. As a particularly powerful mechanism of multidrug resistance, an in-depth examination of efflux pumps is conducted with bacteria of major public health concern including Enterobacteriaceae, Acinetobacter, Neisseria, Pseudomonas, staphylococci, and mycobacteria. The content spans structural biochemistry and transport mechanisms of the major transporter families and considers individual drug efflux systems across various Gram-positive and Gram-negative species. Genomic analysis of efflux pump distribution and their contribution to clinically-relevant resistance are a major focus of the text. Moreover, interplay between drug efflux pumps and other key resistance mechanisms such as intrinsic drug impermeability, inactivation, and target alterations are discussed, as well as their molecular expression-based regulation and physiological functions beyond resistance, involving biofilms, stress response, and pathogenicity. Finally, strategies are addressed to target this drug resistance mechanism with novel antimicrobials or drug inhibitor adjuvants.

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.

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.

The proposed book aims to understand the mechanism of survival of microorganisms in response to chemical stress in various ecological niches that suffer direct human intervention, more so the agricultural, domestic and hospital settings. Microbicides (e.g. disinfectants, antiseptics, fungicides, algaecides, insecticides and pesticides) are used rampantly to control undesirable microbes. Insecticides and pesticides are routinely used in agriculture which directly affect the microbial population in farms, orchards and fields. Health care environments are always stressed with disinfectants and antibiotics. It is always probable that microbicide-stressed microorganisms are in a dynamic state, displaced from one niche to the other. Some soil and water borne bacteria or their resistance determinants are also getting prominence in hospital settings after suffering selective pressure from agricides. In order to reveal the survival strategies of microbicidal-resistant microbes, it is of prime importance to know the mode of action of these complete range of microbicides (agricides to antibiotics). The present book intends to address these issues. There will be several chapters dealing with tolerance and cross resistance in microbes and bacteria in particular, dwelling in various niches. Till date, there is no consensus among scientists in theorizing molecular mechanisms to explain bacterial tolerance and their cross resistance to agricides and antibiotics.

This book is the only single volume to deal with all aspects of gram–positive pathogens. It addresses the mechanisms of gram–positive bacterial pathogenicity, including the current knowledge on gram–positive structure and mechanisms of antibiotic resistance. Emphasizing streptococci, staphylococci, listeria, and spore–forming pathogens, Gram–Positive Pathogens includes chapters written by many of the leading researchers in these areas. The chapters systematically dissect these organisms biologically, genetically, and immunologically in an attempt to understand the strategies used by these bacteria to cause human disease.

Ground-breaking overview of an enduring topic Despite the use of antibiotics, bacterial diseases continue to be a critical issue in public health, and bacterial pathogenesis remains a tantalizing problem for research microbiologists. This new edition of Virulence Mechanisms of Bacterial Pathogens broadly covers the knowledge base surrounding this topic and presents recently unraveled bacterial virulence strategies and cutting-edge therapies. A team of editors, led by USDA scientist Indira Kudva, compiled perspectives from experts to explain the wide variety of mechanisms through which bacterial pathogens cause disease: the host interface, host cell enslavement, and bacterial communication, secretion, defenses, and persistence. A collection of reviews on targeted therapies rounds out the seven sections of this unique book. The new edition provides insights into some of the most recent advances in the area of bacterial pathogenesis, including how metabolism shapes the host-pathogen interface interactions across species and genera mechanisms of the secretion systems evasion, survival, and persistence mechanisms new therapies targeting various adaptive and virulence mechanisms of bacterial pathogens Written to promote discussion, extrapolation, exploration, and multidimensional thinking, Virulence Mechanisms of Bacterial Pathogens serves as a textbook for graduate courses on bacterial pathogenesis and a resource for specialists in bacterial pathogenicity, such as molecular biologists, physician scientists, infectious disease clinicians, dental scientists, veterinarians, molecular biologists, industry researchers, and technicians.

AN AUTHORITATIVE SURVEY OF CURRENT RESEARCH INTO CLINICALLY USEFUL CONVENTIONAL AND NONCONVENTIONAL ANTIBIOTIC THERAPEUTICS Pharmaceutically-active antibiotics revolutionized the treatment of infectious diseases, leading to decreased mortality and increased life expectancy. However, recent years have seen an alarming rise in the number and frequency of antibiotic-resistant "Superbugs." The Centers for Disease Control and Prevention (CDC) estimates that over two million antibiotic-resistant infections occur in the United States annually, resulting in approximately 23,000 deaths. Despite the danger to public health, a minimal number of new antibiotic drugs are currently in development or in clinical trials by major pharmaceutical companies. To prevent reverting back to the pre-antibiotic era—when diseases caused by parasites or infections were virtually untreatable and frequently resulted in death—new and innovative approaches are needed to combat the increasing resistance of pathogenic bacteria to antibiotics. Bacterial Resistance to Antibiotics – From Molecules to Man examines the current state and future direction of research into developing clinically-useful next-generation novel antibiotics. An internationally-recognized team of experts cover topics including glycopeptide antibiotic resistance, anti-tuberculosis agents, anti-virulence therapies, tetracyclines, the molecular and structural determinants of resistance, and more. Presents a multidisciplinary approach for the optimization of novel antibiotics for maximum potency, minimal toxicity, and appropriated degradability Highlights critical aspects that may relieve the problematic medical situation of antibiotic resistance Includes an overview of the genetic and molecular mechanisms of antibiotic resistance Addresses contemporary issues of global public health and longevity Includes full references, author remarks, and color illustrations, graphs, and charts Bacterial Resistance to Antibiotics – From Molecules to Man is a valuable source of up-to-date information for medical practitioners, researchers, academics, and professionals in public health, pharmaceuticals, microbiology, and related fields.