Biological Sciences
Discovery of Antibiotics
The discovery of antibiotics refers to the identification and development of substances that can kill or inhibit the growth of bacteria. This breakthrough has revolutionized medicine by providing effective treatments for bacterial infections. The first antibiotic, penicillin, was discovered by Alexander Fleming in 1928, leading to the subsequent development of numerous other antibiotics that have saved countless lives.
Written by Perlego with AI-assistance
Related key terms
1 of 5
10 Key excerpts on "Discovery of Antibiotics"
eBook - ePubMicrobial Resources
From Functional Existence in Nature to Applications
- Ipek Kurtboke, Ipek Kurtböke(Authors)
- 2017(Publication Date)
- Academic Press(Publisher)
Chapter 7An Overview of the Industrial Aspects of Antibiotic Discovery
Evan Martens*Arnold L. Demain*** Cempra, Inc., Chapel Hill, NC, United States** RISE Institute, Drew University, Madison, NJ, United StatesAbstract
Microorganisms have provided an essential role in the production of natural products, such as antibiotics. Antibiotics are often produced as secondary metabolites, compounds not required for the normal growth and development of the organism. However, they may also be either semisynthetically produced from natural products or chemically synthesized based on the structure of the natural products. Beginning with Alexander Fleming’s discovery of penicillin in 1928, the field of medicine has seen a breakthrough in the different types of antibiotics available to treat bacterial infections. These include β-lactams (penicillins and cephalosporins), tetracyclines, aminoglycosides, chloramphenicol, macrolides, quinolones, and glycopeptides. For over half a century, antibiotics have saved millions of lives, eradicated disease, reduced pain and suffering, and even drastically increased the human life expectancy. Unfortunately, we have seen a decline in the discovery of new and effective antibiotics over the last few decades. Pharmaceutical companies are facing a number of challenges, such as short treatment durations, increased cost of clinical trials, brief window before the products become generics, and the growing problem of antibiotic resistance. Many of the major pharmaceutical companies have abandoned the antibiotic field, leaving much of the discovery efforts to small companies, new companies, and the biotechnology industry. Despite these challenges, other promising opportunities exist for the discovery of new drugs, such as high-throughput screening of natural product libraries, combinatorial chemistry of natural product scaffolds, genomics, proteomics, metabolomics, and discoveries in biodiversity, genome mining, and systems biology. Furthermore, we must also focus our efforts on the vast majority of microorganisms existing in nature that have yet to be cultured in the laboratory, for they too will likely provide us with a rich source of antimicrobials.
- Carlos F. Amabile-Cuevas(Author)
- 2015(Publication Date)
- CRC Press(Publisher)
1.1 A NT I B I OT I C S : ORIGINS AND A CT IV ITY “Antibiotic’’, according to the Merriam-Webster dictionary, is “a substance produced by or a semisynthetic substance derived from a microorganism and able in dilute solu-tion to inhibit or kill another microorganism’’. This definition would encompass things like natural penicillin (a product of a mold) and ampicillin (a semisynthetic derivative of penicillin); exclude entirely synthetic agents such as sulfonamides and quinolones; and leave in a limbo drugs like chloramphenicol which, although initially discovered as a product of soil bacteria, it is now produced entirely by chemical synthesis. A wider definition from Wikipedia states that “antibiotics [ . . . ] are a type of antimicrobial used in the treatment or prevention of bacterial infection’’, whereas “antimicrobial’’ is sim-ply “an agent that kills microorganisms or inhibits their growth’’, which would also 2 Antibiotics and Antibiotic Resistance in the Environment include antiseptics and disinfectants. Then there are “antibacterials’’, “anti-infective chemotherapy’’, and so on. For the purposes of this book, as there is no evident advan-tage in discriminating at every sentence between natural and synthetic compounds, an antibiotic would be a chemical agent with a selective toxicity profile, capable of killing or inhibiting the growth of bacteria but mostly incapable of exerting toxicity upon eukaryotic cells at the same concentration (the “magic bullet’’ imagined by Paul Ehrlich), that is commonly used to treat or prevent bacterial infections. This definition would therefore include all drugs, of natural or synthetic origin, used against bacte-ria; and would exclude compounds used against viruses, fungi, protozoans or other microorganisms, as well as non-selective biocides, such as disinfectants and antiseptics.
eBook - PDF- Varaprasad Bobbarala(Author)
- 2012(Publication Date)
- IntechOpen(Publisher)
BC-3781 is being developed for both oral and intravenous formulations. 4. How do we search for natural antibiotics? Although the number of antibiotics present in nature may truly be huge, many of them are already known or will not be usable (i.e., will not display selective toxicity to bacteria, will be too weak, or will lack the desired pharmacokinetic properties) (Pelaez, 2006). Yet historically, the development of antibiotics from natural templates has seen an unprecedented gain compared to the de novo synthesis. The conventional discovery process of antibiotics from the pool of microbial natural products requires having a given microorganism grown in conditions appropriate to induce the production of (the desired) metabolite, which is then extracted and tested in a screen able to detect it as a hit. Finally, the compound has to be isolated from the original mixture and identified. Identification of novel antibiotic types that occur in relatively low frequency in nature clearly requires innovative detection and characterization techniques. Numerous promising microbiological approaches supplemented with bioinformatic, genetic, and structural methods have been developed over the last decade to address the issue (Fig. 3). Fig. 3. Postgenomic approaches in antibiotic discovery (adapted from (Davies, 2011)). Antimicrobial Agents 38 These allow for laboratory culturing of previously inaccessible microorganisms as potential antibiotic producers, extracting genomes of uncultivable species from environmental samples or mining for and inducing expression of cryptic biosynthetic clusters to yield yet untapped secondary metabolites, direct solvent extraction and subsequent characterization of low molecular weight compounds from natural samples, and high-throughput fermentation of underexplored bacterial strains. In addition, intelligent strategies to avoid antibiotic rediscovery have been devised.
eBook - PDFBovine Science
A Key to Sustainable Development
- Sadashiv S. O., Sharangouda J. Patil, Sadashiv S. O., Sharangouda J. Patil(Authors)
- 2019(Publication Date)
- IntechOpen(Publisher)
Since the discovery of the first antibiotic, penicillin (1920s), researcher worked diligently to find new antibiotics, and this leads to the discovery of many new antibiotics, e.g., tetracycline, gentamicin, and chloramphenicol. Antibiotics are compounds which are produced by one microbe, and they are used to kill the other microbial spp. So, till 1950 a majority of infectious diseases in humans were treatable by using these antibiotics [1]. However, unfortunately, soon after the clinical use of antibiotics, a phenomenon was found in Staphylococcus aureus by means of which it was no longer susceptible to penicillin. It started producing an enzyme named as penicillinase, which can easily break down the beta lactam ring of penicillin. This ring is necessary to bind bacteria (penicillin binding proteins; PBPs) and therefore its bacterial killing ability. This effect was named as antimicrobial/antibiotic resistance in bacteria. Since then, many different types of bacteria are becoming increasingly resistant to many new antibiotics. The phenomenon of antibiotic resistance in bacteria is a persistently ongoing process and is on rise with every new day. This process can further be increased by humans, e.g., the inappropriate use of antibiotics, following reduced doses of antibiotics than required/standards, using antibiotics as a precautionary measures in viral infections, using antibiotics as growth promoters, prescribing broad-spectrum antibiotics, using antibiotics with-out using the antimicrobial sensitivity testing, and finally by noncompliance of the animal owner. There has been a surge in the use of antibiotics for treatment of a variety of infections. In fact, nowadays, the use of a variety of anti-infection therapy has become an invaluable tool for the treatment of a variety of bovine infections. Using anti-infective agents has greatly reduced the mortality as well as the morbidity against a variety of microbial infections in animals and humans.
eBook - PDF- Preethi Kartan(Author)
- 2019(Publication Date)
- Delve Publishing(Publisher)
The chapter below outlines all those micro-organisms that act as the building blocks of biotechnology and would be required for producing antibiotics. 5.1 INTRODUCTION Natural product compounds (NPCs), particularly obtained from micro-or-ganisms (like bacteria and lower eukaryotes) are important resources for many medicines. Drugs derived from such microbial origin have been cat-egorized into three types of products: • original microbial products, • products derived or chemically processed from microbial products, • synthetic products based on microbial product structures. Initial scientific researches in the field of soil microflora (the intimate part of soil organic matter, consisting of live and dead microbial cells) made scientists wonder on the presence of some compound that held the key to their survival. The soil, regardless of joining with billions of microorganisms, enables only some of them to endure the struggle for existence. Recently, many chemical compounds utilized in the treatment and management of cancer, infections due to drug-resistant microbes (bacteria, fungi, and viruses), and immunosuppressive disorders, are extracted from microbial sources. Researches and experiments led to the concept of ‘‘antibiosis’’. The term antibiosis means ‘against life’. The famous Nobel Prize winner, Selman Abraham Waksman, invented the term ‘‘antibiotic’’. Introduction of microbial antibiotic as like penicillin and streptomycin confirmed the affirmation that microorganisms should be experimented upon more for new and unique bioactive compounds for the treatment of terminal diseases. The pharmaceutical industry is deeply influenced by the development of antibacterial drugs, and as a result, the market is filled with old drug scaffolds. Basically, the scaffold of a molecule is taken to be its framework, defined as all its ring systems and all linkers that connect them.
eBook - PDF- Richard G. Wax, Kim Lewis, Abigail A. Salyers, Harry Taber, Richard G. Wax, Kim Lewis, Abigail A. Salyers, Harry Taber(Authors)
- 2007(Publication Date)
- CRC Press(Publisher)
THE DRUG DISCOVERY AND DEVELOPMENT PROCESS The goal of the antibacterial drug discovery process is simple in concept: ( i ) Find agents that inhibit bacterial growth and/or kill bacteria. ( ii ) Determine whether these agents work in animal models of infection without outright toxicity. ( iii ) Test them in humans with defined and documented bacterial infections compared to existing therapies. But how does one approach this process, that is, find those specific, non-toxic inhibitors of bacterial growth? THE OLD-FASHIONED WAY The time-honored (and validated) method is to screen a series of chemical compounds (or natural product extracts) for antibacterial activity initially in vitro (and then in Antibacterial Drug Discovery in the 21st Century 413 animal models of disease). All of the antibacterial drugs currently used therapeutically were identified by variations of this method or by synthetic modifications of agents identified by this method. Once such agents have been identified, it is typical to make, via medicinal chemistry, variants of the initial “hit,” and this is true whether one is working with a synthetic chemical starting point or a natural product. In almost all cases, new medical entities (NMEs) can be generated with activities superior to the original compound, and increases in potency or improvements in pharmacokinetics of 1000-fold are not unusual. Therefore, any antibacterial drug discovery program that lacks a synthetic chemistry component will, at best, have limited success. THE NEW-FANGLED APPROACH— TARGET-BASED DRUG DISCOVERY U SING P OST -G ENOMIC T ECHNOLOGIES FOR T ARGET -B ASED D RUG D ISCOVERY [6] One critical point that cannot be repeated often enough is that any target-based assay must be more sensitive than is achieved by merely screening compounds for frank growth inhibition (“it’s the assay, stupid”).
eBook - PDF- Nina Parker, Mark Schneegurt, Anh-Hue Thi Tu, Brian M. Forster, Philip Lister(Authors)
- 2016(Publication Date)
- Openstax(Publisher)
• Antibiograms are useful for monitoring local trends in antimicrobial resistance/susceptibility and for directing appropriate selection of empiric antibacterial therapy. • There are several laboratory methods available for determining the minimum inhibitory concentration (MIC) of an antimicrobial drug against a specific microbe. The minimal bactericidal concentration (MBC) can also be determined, typically as a follow-up experiment to MIC determination using the tube dilution method. 14.7 Current Strategies for Antimicrobial Discovery • Current research into the development of antimicrobial drugs involves the use of high-throughput screening and combinatorial chemistry technologies. Chapter 14 | Antimicrobial Drugs 651 • New technologies are being developed to discover novel antibiotics from soil microorganisms that cannot be cultured by standard laboratory methods. • Additional strategies include searching for antibiotics from sources other than soil, identifying new antibacterial targets, using combinatorial chemistry to develop novel drugs, developing drugs that inhibit resistance mechanisms, and developing drugs that target virulence factors and hold infections in check. Multiple Choice 1. A scientist discovers that a soil bacterium he has been studying produces an antimicrobial that kills gram- negative bacteria. She isolates and purifies the antimicrobial compound, then chemically converts a chemical side chain to a hydroxyl group. When she tests the antimicrobial properties of this new version, she finds that this antimicrobial drug can now also kill gram-positive bacteria. The new antimicrobial drug with broad-spectrum activity is considered to be which of the following? a. resistant b. semisynthetic c. synthetic d. natural 2. Which of the following antimicrobial drugs is synthetic? a. sulfanilamide b. penicillin c. actinomycin d. neomycin 3. Which of the following combinations would most likely contribute to the development of a superinfection? a.
eBook - PDF- Bozzano G Luisa(Author)
- 2012(Publication Date)
- Academic Press(Publisher)
The antibiotic assay has SEARCH AND DISCOVERY OF NEW ANTIBIOTICS 35 been innovatively and continually improved to detect target antibiotics even at low concentrations. The use of hypersensitive mutants and specific enzymatic assays to detect target /^-lactam antibiotics are representative of this approach. Furthermore, the progress in isolation technology and instrumental analysis of antibiotics have made it possible to extract, purify and identify unstable antibiotics, as well as those present as minor products. New methodologies such as mutasynthesis, cell fusion and gene manipulation, that have been introduced to the study of streptomycetes during the 1970s and 1980s, have contributed substantially to the discovery of additional antibiotics. The new antibiotics discovered in the 1970s are structurally related to known antibiotics. The discovery of new antibiotics will therefore require sophisticated methods to select naturally occurring actinomycetes capable of producing antibiotics whose structures are similar to, but distinct from, known antibiotics and/or methods to distinguish culture broths containing such antibiotics. More information will be needed on, and either insight or hindsight into, the microbiological, biochemical and/or genetic backgrounds or concepts in order to improve screening programmes and actinomycete manipulation. This chapter focuses on how methodological improvements are related to these backgrounds or concepts in the search and discovery of new antibiotics. 2. General Remarks on the Background of Antibiotic Production by Actinomycetes Actinomycetes produce large numbers of antibiotics with a wide variety of chemical structures. However, not all actinomycete strains produce TABLE 1.
eBook - PDF- Selman A. Waksman(Author)
- 2023(Publication Date)
- University of California Press(Publisher)
These chemical substances, designated as "antibiotics," were then tested for their activity against different bacteria, in- cluding pathogenic forms. Their effect was found to vary greatly, depending on the chemical and biological characteristics of the substances and the specific nature of the organisms used for test- ing purposes. After certain preliminary studies on the antagonistic inter- relations among soil microbes that were carried out in my labora- tory for nearly a decade, I began in 1939 a systematic search for various saprophytic microbes, largely those found in the soil or in the dust, that had the capacity to prevent the growth of other microbes, notably disease-producing bacteria. In this work, I had the help of a number of graduate students and assistants, without whose collaboration such extensive studies would never have been possible. It is sufficient to mention H. B. Woodruff, H. Robinson, Elizabeth S. Horning, Doris Jones, A. Schatz, H. Christine Reilly, Elizabeth Bugie, D. B. Johnstone, O. E. Graessle, and Dorothy R. Smith. I paid particular attention to one group of microbes occurring extensively in soil, namely the actinomycetes. These filamentous branching bacteria are frequently spoken of, quite incorrectly, as "soil molds." There were two important reasons why I used largely these microbes as potential producers of antibiotics: 1 1 4 T H E A D V E N T OF A N T I B I O T I C S I . I had been familiar with the nature and activities of actino- mycetes for nearly a quarter of a century, or since 1914, when I first undertook experiments on the occurrence and biochemi- cal activities of soil microbes at Rutgers as an undergraduate and then as a graduate student, and later (in 1916) at the University of California, where I obtained my Ph.D. degree. 2. By a sheer stroke of good fortune, the actinomycetes proved to be highly productive of antibiotic substances.
eBook - PDF- Smith, P(Authors)
- 2018(Publication Date)
- Agri Horti Press(Publisher)
16 Advances in Applied Biotechnology and Microbiology The high demand for chemotherapeutic agents to treat wound infections during World War II led to the development of a production process for penicillin and this marked the beginning of an era of antibiotic research and continues to be the most fascinating area of microbial biotechnology even today. Among the antibiotics discovered, the most extensively used are the penicillins, cephalosporins, tetracyclines and erythromycins. As we know, antibiotics are produced in a culture medium during the idiophase due to depletion caused by one or more nutrients in the medium. According to Perlman, antibiotic biosynthesis can be considered as a result of a series of in-born errors of metabolism. The original microorganisms can be subjected to mutagenic agents, and thereby the errors can be exaggerated so as to get large quantities of antibiotics. However, high yield of commercially important antibiotics is due to selection of improved mutant strains and their culture. For example improved strain of Penicillium chrysogenum yields 20 mg/ml of benzyl penicillin rather than the normal rate of 720 g/ ml. -exotoxin is a crystalline, water-soluble, proteinaceous toxin secreted by Bacillus thuringiensis. They interrupt the metabolism of host cells and destroy the structural integrity of cell. -exotoxin is active against flies and mosquitoes (Diptera), beetles (Coleoptera), termites (Orthoptera), butterflies and moths (Lepidoptera). No mammal (including man) is affected by this proteinaceous toxin, hence the secretions of the stomach converts it into a non-toxic form. The production of -exotoxin on a large scale is easy. B. thuringiensis is cultured in a nutrient medium and is supplemented with starch, hence this bacterium secretes amylolytic enzymes. The fluid is filtered after completion of the bacterial growth and the final product is obtained from the filtrate by vacuum drying.
Index pages curate the most relevant extracts from our library of academic textbooks. They’ve been created using an in-house natural language model (NLM), each adding context and meaning to key research topics.
