Discovering Antibacterial and Anti-resistance Agents Targeting Multi-drug Resistant ESKAPE Pathogens PDF Download

Author: Renee Marie Fleeman
Publisher:
ISBN:
Category : Anti-infective agents
Languages : en
Pages : 138

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Book Description
Antibiotic resistance has been a developing problem for mankind in recent decades and multi-drug resistant bacteria are now encountered that are resistant to all treatment options available. In 2014, the World Health Organization announced that this problem is driving us towards a “post-antibiotic era” that will change the face of modern medicine as we know it. If lack of novel antibiotic development and FDA approval continues, by the year 2050, 10 million people will die each year to an antimicrobial resistant bacterial infection. With lack of pharmaceutical industry involvement in developing novel antibiotics, the responsibility now lies within the academic institutions to identify potential novel therapeutics to fuel the antibiotic drug discovery pipeline. Combinatorial chemistry is one technique used to expedite the discovery process by assessing a large chemical space in a relatively short time when compared to traditional screening approaches. Combinatorial libraries can be screened using multiple approaches and has shown successful application towards many disease states. We initially discovered broad spectrum antibacterial bis-cyclic guanidines using combinatorial libraries and expanded on the knowledge of the physiochemical attributes necessary to inhibit Gram negative bacterial pathogens. Following this success, we continued to assess the combinatorial libraries for adjunctive therapeutics that potentiate the activity of obsolete clinical antibiotics. The polyamine efflux pump inhibitors discovered in this subsequent study prove the benefits of using the large chemical space provided in the combinatorial libraries to identify a variety of therapeutics. Our studies always begin with identifying an active compound and active compounds undergo hit-to-lead optimization. This optimization studies are of utmost importance in developing a novel antibacterial agent for therapeutic applications. Our medicinal chemistry work described here is proof of the success of careful structure activity analyses to optimize a hit scaffold to create a more effective antibacterial agent. Overall, our work described here reveals the potential role of academic institutions in fending off the impending “post-antibiotic era”.

Author: Prashant Kesharwani
Publisher: Academic Press
ISBN: 0128184817
Category : Medical
Languages : en
Pages : 434

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Book Description
Drug Discovery Targeting Drug-Resistant Bacteria explores the status and possible future of developments in fighting drug-resistant bacteria. The book covers the majority of microbial diseases and the drugs targeting them. In addition, it discusses the potential targeting strategies and innovative approaches to address drug resistance. It brings together academic and industrial experts working on discovering and developing drugs targeting drug-resistant (DR) bacterial pathogens. New drugs active against drug-resistant pathogens are discussed, along with new strategies being used to discover molecules acting via new modes of action. In addition, alternative therapies such as peptides and phages are included. Pharmaceutical scientists, microbiologists, medical professionals, pathologists, researchers in the field of drug discovery, infectious diseases and microbial drug discovery both in academia and in industrial settings will find this book helpful. Written by scientists with extensive industrial experience in drug discovery Provides a balanced view of the field, including its challenges and future directions Includes a special chapter on the identification and development of drugs against pathogens which exhibit the potential to be used as weapons of war

Author: Iqbal Ahmad
Publisher: Springer Nature
ISBN: 9811398712
Category : Medical
Languages : en
Pages : 680

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Book Description
This book compiles the latest information in the field of antibacterial discovery, especially with regard to the looming threat of multi-drug resistance. The respective chapters highlight the discovery of new antibacterial and anti-infective compounds derived from microbes, plants, and other natural sources. The potential applications of nanotechnology to the fields of antibacterial discovery and drug delivery are also discussed, and one section of the book is dedicated to the use of computational tools and metagenomics in antibiotic drug discovery. Techniques for efficient drug delivery are also covered. The book provides a comprehensive overview of the progress made in both antibacterial discovery and delivery, making it a valuable resource for academic researchers, as well as those working in the pharmaceutical industry.

Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309185343
Category : Medical
Languages : en
Pages : 497

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Book Description
Years of using, misusing, and overusing antibiotics and other antimicrobial drugs has led to the emergence of multidrug-resistant 'superbugs.' The IOM's Forum on Microbial Threats held a public workshop April 6-7 to discuss the nature and sources of drug-resistant pathogens, the implications for global health, and the strategies to lessen the current and future impact of these superbugs.

Author: Grewal, Ajmer Singh
Publisher: IGI Global
ISBN:
Category : Medical
Languages : en
Pages : 442

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Book Description
The rise of modern antimicrobial drug resistance has evolved into a pressing global health crisis, challenging the very foundation of our ability to combat infectious diseases. The overuse and accessibility of antibiotics, particularly in emerging nations, have given rise to resilient "superbugs," rendering common medications ineffective. This escalating challenge poses a significant threat to public health and leads to heightened healthcare costs, prolonged patient stays, and increased mortality rates. As communities grapple with the urgent need for a coordinated response, a comprehensive understanding of antimicrobial drug resistance and innovative strategies becomes paramount. Frontiers in Combating Antibacterial Resistance: Current Perspectives and Future Horizons is meticulously crafted for academic scholars, researchers, and healthcare professionals. It addresses this critical issue head-on and serves as a beacon of knowledge and a solution-oriented guide. With a focus on elucidating the mechanisms behind antimicrobial drug resistance and exploring emerging therapeutic targets, the book presents an in-depth analysis of the problem. It spans environmental, genetic, and climatic factors influencing resistance, delving into cutting-edge technologies and sustainable strategies for prevention. By offering a holistic view of the issue and proposing evidence-based solutions, the book is an indispensable resource for those seeking to navigate the complex landscape of antimicrobial drug resistance.

Author: G. Tegos
Publisher: CABI
ISBN: 9781780640310
Category : Anti-infective agents
Languages : en
Pages : 369

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Book Description
Drug resistance is increasing among a variety of human pathogenic microorganisms such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumaniii, Pseudomonas aeruginosa and Enterobacter spp. (currently dubbed the 'ESKAPE' pathogens), and has emerged as one of the most important clinical challenges of this century. Increased general awareness and fear of these pathogens means there is a growing demand for research to tackle the threat of multidrug resistance. Documenting the latest research in the field, this book discusses current and promising activities to discover new antimicrobials in five key areas: molecular genetics and systems microbiology; synthetic, computational chemistry and chemoinformatics; High Throughput Screening (HTS); non-vertebrate model hosts; and light- and nano-based technologies.

Author: Flavia Marinelli
Publisher: Springer Science & Business Media
ISBN: 3642399681
Category : Medical
Languages : en
Pages : 363

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Book Description
Reports on the emergence and prevalence of resistant bacterial infections in hospitals and communities raise concerns that we may soon no longer be able to rely on antibiotics as a way to control infectious diseases. Effective medical care would require the constant introduction of novel antibiotics to keep up in the “arms race” with resistant pathogens. This book closely examines the latest developments in the field of antibacterial research and development. It starts with an overview of the growing prevalence of resistant Gram-positive and Gram-negative pathogens, including their various resistance mechanisms, prevalence, risk factors and therapeutic options. The focus then shifts to a comprehensive description of all major chemical classes with antibacterial properties, their chemistry, mode of action, and the generation of analogs; information that provides the basis for the design of improved molecules to defeat microbial infections and combat the emerging resistances. In closing, recently developed compounds already in clinical use, those in preclinical or first clinical studies, and a number of promising targets to be exploited in the discovery stage are discussed.

Author: Grewal, Ajmer Singh
Publisher: IGI Global
ISBN:
Category : Medical
Languages : en
Pages : 384

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Book Description
In infectious disease management, antibacterial agents have long been viewed as pivotal tools in the relentless battle against microorganisms. However, the escalating threat of antibacterial drug resistance has emerged as a formidable challenge to global health. Contemporary Approaches to Mitigating Antibacterial Drug Resistance delves into the heart of this critical issue, exploring the mechanisms, consequences, and innovative strategies to counteract the surge of resistance, a phenomenon becoming increasingly pervasive and threatening worldwide. Antibacterial drug resistance, a pressing public health concern, transcends geographical boundaries. In regions where antibiotic accessibility and overuse prevail, resistance rates soar, giving rise to the ominous "superbugs." This book unravels the intricacies of drug resistance, examining its impact on infectious disease management, healthcare economics, and societal well-being. The exploration begins with a foundational understanding of antibacterial drug resistance, navigating through the intricate mechanisms that drive its rapid proliferation. Environmental and genetic factors, often overlooked, are dissected for their roles in fostering resistance. The book explores the interplay of antibacterial drugs with micro-biodiversity, shedding light on the indirect repercussions on human and environmental ecosystems. The primary audience, encompassing undergraduate and postgraduate students, medical practitioners, academicians, and researchers, will find in-depth insights into emerging therapeutic targets and recent advances in drug development. The secondary audience, including authorities in antibacterial drug resistance and institutional libraries, will discover a valuable resource addressing the multifaceted dimensions of this global menace.

Author: Trent A. Kunkle
Publisher:
ISBN:
Category :
Languages : en
Pages : 146

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Book Description
The Centers for Disease Control (CDC) and World Health Organizations (WHO) have highlighted six species of highly drug-resistant bacteria, commonly termed the ESKAPE pathogens, that new antibacterials are urgently needed to treat). The ESKAPE pathogens account for over two-million infections and have healthcare costs upwards of $20 billion dollars annually. Over the past several decades, pharmaceutical companies have drastically reduced their research programs for developing new antibacterial agents. As well, bacteria are predisposed to rapidly generate resistance against these "me too" drugs, making this strategy a temporary stop-gap in our ability to fight these pathogens. This has left the burden to identify new antibiotics that function through fundamentally unique mechanisms of action to academia. Towards this goal, we are developing a unique antibacterial strategy that functions through targeting the bacterial GroEL chaperonin systems. GroEL is a molecular chaperone that helps fold proteins into their functional states. Being an essential protein, inhibiting GroEL activity leads to global aggregation and bacterial cell death. We previously reported a high-throughput screening effort that identified 235 GroEL inhibitors. A subsequent study with a subset of these inhibitors identified several that kill bacteria. To follow-up, we have synthesized 43 analogs of a hit-to-lead molecule, compound 1, containing systematic deletions of substituents and substructures to determine the essential parts of the scaffold for inhibiting GroEL and killing bacteria. Along with inhibiting GroEL, several compound 1 analogs exhibit>50-fold therapeutic windows between antibacterial efficacy and cytotoxicity to human liver and kidney cells in cell culture. Evaluation of two lead candidates (1 and 11) in a gain-of-resistance assay indicated that MRSA bacteria were not able to easily generate resistance to this compound class. Compound 1 also exhibited the ability to permeate through already established S. aureus biofilms and maintain its bactericidal effects, whereas vancomycin could not. Having established initial structure-activity relationships for the compound 1 substituents and substructures in this study, future efforts will focus on optimizing the antibacterial effects of lead candidates and reducing their off-target toxicity to human cells

Author: Rosaleen Anderson
Publisher: John Wiley & Sons
ISBN: 1118325443
Category : Science
Languages : en
Pages : 379

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Book Description
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.