Antibiotics

May 27, 2010 by  


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In common usage, an antibiotic (from the Ancient Greek: ἀντί – anti, “against”, and βίος – bios, “life”) is a substance or compound that killsbacteria or inhibits its growth. Antibiotics belong to the broader group of antimicrobial compounds, used to treat infections caused bymicroorganisms, including fungi and protozoa.

The term “antibiotic” was coined by Selman Waksman in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution. This original definition excluded naturally occurring substances that kill bacteria but are not produced by microorganisms (such as gastric juice and hydrogen peroxide) and also excluded synthetic antibacterial compounds such as the sulfonamides. Many antibiotics are relatively small molecules with a molecular weight less than 2000 Da.

With advances in medicinal chemistry, most antibiotics are now semisynthetic—modified chemically from original compounds found in nature, as is the case with beta-lactams (which include the penicillins, produced by fungi in the genus Penicillium, the cephalosporins, and the carbapenems). Some antibiotics are still produced and isolated from living organisms, such as the aminoglycosides, and others have been created through purely synthetic means: the sulfonamides, the quinolones, and the oxazolidinones. In addition to this origin-based classification into natural, semisynthetic, and synthetic, antibiotics may be divided into two broad groups according to their effect on microorganisms: those that kill bacteria are bactericidal agents, while those that only impair bacterial growth are known as bacteriostatic agents.

Many treatments for infections prior to the beginning of the twentieth century were based on medicinal folklore. Treatments for infection in ancient Chinese medicine using plants with antimicrobial properties were described over 2,500 years ago. Many other ancient cultures, including the ancient Egyptians and ancient Greeks used molds and plants to treat infections. The discovery of the natural antibiotics produced by microorganisms stemmed from earlier work on the observation of antibiosis between micro-organisms. Pasteur observed that “if we could intervene in the antagonism observed between some bacteria, it would offer ‘perhaps the greatest hopes for therapeutics’”. Synthetic antibiotic chemotherapy as a science and the story of antibiotic development began in Germany with Paul Ehrlich, a German medical scientist in the late 1880s. Scientific endeavours to understand the science behind what caused these diseases, the development of synthetic antibiotic chemotherapy, the isolation of the natural antibiotics marked milestones in antibiotic development.

Originally known as antibiosis, antibiotics were drugs that had actions against bacteria. The term antibiosis, which means “against life,” was introduced by the French bacteriologist Vuillemin as a descriptive name of the phenomenon exhibited by these drugs. (Antibiosis was first described in 1877 in bacteria when Louis Pasteur and Robert Koch observed that an airborne bacillus could inhibit the growth of Bacillus anthracis.). These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist in 1942.

Bacterial antagonism of Penicillium spp. were first described in England by John Tyndall in 1875. The significance to antibiotic discovery was not realized until the work of Ehrlich on synthetic antibiotic chemotherapy, which marked the birth of the antibiotic revolution. Ehrlich noted that certain dyes would bind to and color human, animal or bacterial cells, while others did not. He then extended the idea that it might be possible to make certain dyes or chemicals that would act as a magic bullet or selective drug that would bind to and kill bacteria while not harming the human host. After much experimentation, screening hundreds of dyes against various organisms, he discovered a medicinally useful drug, the man-made antibiotic, Salvarsan. In 1928 Fleming made an important observation concerning the antibiosis by penicillin. Fleming postulated the effect was mediated by a yet unidentified antibiotic like compound which could be exploited a naturally occurring antibiotic although he initially characterised some of its antibiotic properties he didn’t pursue its development. In the meantime, another synthetic antibacterial antibiotic Prontosil was developed and manufactured for commercial use by Domagk in 1932. Prontosil, the first commercially available antibacterial antibiotic was developed by a research team led by Gerhard Domagk (who received the 1939 Nobel Prize for Medicine for his efforts) at the Bayer Laboratories of the IG Farben conglomerate in Germany. Prontosil had a relatively broad effect against Gram-positivecocci but not against enterobacteria. The discovery and development of this first sulfonamide drug opened the era of antibiotics. In 1939 discovery by Rene Dubos of the first naturally derived antibiotic like substance named gramicidin from B. brevis. It was one of the first commercially manufactured antibiotics in use during World War II to prove highly effective in treating wounds and ulcers.[16] Florey and Chain succeeded in purifying penicillin. The purified antibiotic displayed antibacterial activity against a wide range of bacteria. It also had low toxicity and could be taken without causing adverse effects. Furthermore its activity was not inhibited by biological constituents such as pus, unlike the synthetic antibiotic class available at the time the sulfonamides. The discovery of such a powerful antibiotic was unprecedented. The development of penicillin led to renewed interest in the search for antibiotic compounds with similar capabilities.[17] Because of their discovery of penicillin Ernst Chain, Howard Florey and Alexander Fleming shared the 1945 Nobel Prize in Medicine. Florey credited Dubos with pioneering the approach of deliberately, systematically searching for antibacterial compounds. Such a methodology had led to the discovery of gramicidin, which revived Florey’s research in penicillin.[

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