Division 2.qxd
Transcrição
Division 2.qxd
1929 On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to Their Use in the Isolation of B. influenzae A. FLEMING Reprinted with permission from British Journal of Experimental Pathology 10:226–236. (Now International Journal of Experimental Pathology.) Copyright © 1929. Blackwell Science Ltd. 1940 Penicillin as a Chemotherapeutic Agent E. CHAIN, H. W. FLOREY, A. D. GARDNER, N. G. HEATLEY, M. A. JENNINGS, J. ORR-EWING, AND A. G. SANDERS Reprinted with permission from Lancet ii:226–228. Copyright © 1940. The Lancet Ltd. An Enzyme from Bacteria Able To Destroy Penicillin E. P. ABRAHAM AND E. CHAIN Reprinted by permission from Nature 146:837. Copyright © 1940. Macmillan Magazines Ltd. T he first, oft-cited publication by Fleming is believed to be the first report of the antibacterial action of a fungal product. This paper is particularly pleasing to the bench microbiologists among us, who teach our students to be alert for the unexpected. Fleming made the observation that when bacterial culture plates streaked with Staphylococcus were left on a lab bench for an extended period, mold, identified subsequently as Penicillium, developed on the plates and caused lysis of the staphylococcal colonies. He showed that broth in which the Penicillium had been grown at room temperature for 2 weeks was bacteriocidal and bacteriolytic against certain pyogenic cocci (e.g., Streptococcus pyogenes, Streptococcus pneumoniae, and Staphylococcus aureus) as well as the diphtheria bacillus (now called Corynebacterium diphtheriae) but was inactive against many gram-negative organisms. Fleming named the antibacterial substance penicillin, and he showed that it was not toxic to animals when given at very high doses. In his discussion, Fleming proposed that penicillin might be applied to the dressing of wounds. However, he foresaw the major immediate use of penicillin as a means of reducing the growth of penicillin-susceptible flora from sputum to facilitate isolation of such penicillin-resistant agents as Pfiffers bacillus of influenza (now called Haemophilus influenzae). In the second publication, Chain and coworkers followed up on Fleming’s observations with the clear intent of investigating the use of penicillin as a therapeutic agent to treat systemic bacterial infections. They resuscitated his mold cultures, purified penicillin from broth supernatants, and showed that the substance could be used to treat infections in animals. Systemic infections in mice caused by staphylococci, streptococci, and clostridia were dramatically cured by penicillin. Finally, a footnote to these dramatic discoveries is the letter to the editor of Nature from Abraham and Chain describing a substance in B. coli (now Escherichia coli) that could inactivate penicillin. Penicillinase was the first bacterial product isolated that mediated resistance to an antibacterial agent, and this paper foreshadowed the era, 15 years later, of widespread resistance of staphylococci to penicillin. For their seminal discoveries, Fleming, Chain, and Florey were corecipients of the Nobel Prize in Physiology and Medicine in 1945. GORDON ARCHER AND ALISON O’BRIEN 98 Microbiology: A Centenary Perspective Pathogenesis and Host Response Mechanisms 99 100 Microbiology: A Centenary Perspective Pathogenesis and Host Response Mechanisms 101 102 Microbiology: A Centenary Perspective Pathogenesis and Host Response Mechanisms 103 104 Microbiology: A Centenary Perspective Pathogenesis and Host Response Mechanisms 105 106 Microbiology: A Centenary Perspective Pathogenesis and Host Response Mechanisms 107 108 Microbiology: A Centenary Perspective Pathogenesis and Host Response Mechanisms 109 110 Microbiology: A Centenary Perspective Pathogenesis and Host Response Mechanisms 111 112 Microbiology: A Centenary Perspective Pathogenesis and Host Response Mechanisms 113 114 Microbiology: A Centenary Perspective Pathogenesis and Host Response Mechanisms 115
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