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
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100 Microbiology: A Centenary Perspective
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102 Microbiology: A Centenary Perspective
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