The Nature of the Antibiotic Substances Produced by Aspergillus fumigatus

Abstract

The formation of more than one antibiotic substance by a single antagonistic organism has been definitely established. Penicillium notatum, for example, has been shown to produce penicillin and notatin; and Aspergillus flavus, aspergillic acid and flavicin. The ability of different micro6rganisms to produce the same, or a closely related, antibiotic substance has also been demonstrated, as illustrated by the fact that penicillin and flavicin, two of the substances just mentioned as being produced by two distinctly different micro6rganisms, are similar, if not identical, chemically as well as biologically. Another and even more striking illustration is offered, in this connection, by Aspergillusfumigatus. This organism has now been shown to produce four distinctly different antibiotic substances, two of which are closely related chemically. Oxford and Raistrick (1942) found that certain strains of A. fumigatus are able to produce spinulosin and fumigatin, pigmented quinones, both of which possess antibacterial properties. The first possesses only weak antibiotic activity; the second is more active, being capable of bringing about the complete inhibition of growth of certain strains of Staphylococcus aureus in dilutions of 1:50,000. The bacteriostatic action of fumigatin against Escherichia coli is very limited, howe'ver. Waksman, Homing, and Spencer (1943) isolated from the culture filtrate of A. fumigatus grown in a simple synthetic medium a colorless easily crystallizable compound that showed much greater antibacterial activity than fumigatin; this substance, designated as fumigacin, was active largely against various gram-positive bacteria, which were inhibited in a dilution of 1:750,000 to 1:4,000,000; gram-negative bacteria were only slightly affected. Fumigacin contained a small amount of nitrogen and showed some toxicity to animals. Recently, Menzel, Wintersteiner, and Hoogerheide (1944) demonstrated that A, fumigatus produces a fourth compound, namely gliotoxin, a substance that previously was isolated from certain strains of Trichoderma and Gliocladium by Weindling (Weindling and Emerson, 1936). Gliotoxin contains 8.59 per cent nitrogen and 19.65 per cent sulfur. These investigators demonstrated that the crystalline preparation of fumigacin obtained by Waksman, Horning, and Spencer (1943) contains about 20 per cent of a gliotoxin fraction. This accom-

Agar-Streak Method for Assaying Antibiotic Substances

“…Ceram. Soc., 18, 341 (1935), (11) Scholes and Wessels, Chemist-Analyst, 25, 38 (1936). ( 12) Shead and Smith, J.…”

Colorants Produced by Penicillium murcianum Are a Natural Moldicide against Trichoderma and Other Penicillium Species

“…Many of the non-melanin based fungal pigments are quinones of some form, or very closely related. Some examples include yellow-brown fumigatin, a quinone from Aspergillus fumigatus Fresen [6][7][8][9], auroglaucin (orange-red), flavoglaucin (yellow), rubroglaucin (red) from Aspergillus glaucus (L.) [10], islandicin (green to red) from Penicillium islandicum Sopp. [11][12][13][14], xylindein (blue-green) from Chlorociboria species [15], and dramada (redorange crystal) from Scytalidium cuboideum (Sacc.…”