Selman A. Waksman

Streptomycin, a Substance Exhibiting Antibiotic Activity Against Gram-Positive and Gram-Negative Bacteria.∗†:

Summary A new antibacterial substance, designated as streptomycin, was isolated from two strains of an actinomyces related to an organism described as Actinomyces griseus. This substance resembles streptothricin in its solubility in water, mode of isolation and concentration from culture medium, its selective activity against gram-negative bacteria, and its limited toxicity to animals. However, the two substances differ in the nature of their respective bacteriostatic spectra as well as in their quantitative action upon different bacteria. It is suggested that one is dealing here with two closely related chemical compounds.

Effect of Streptomycin and Other Antibiotic Substances upon Mycobacterium tuberculosis and Related Organisms.

Summary Mycobacterium tuberculosis is subject to the bacteriostatic action of a variety of antibiotic substances. There is considerable variation in this respect, both in the sensitivity of the same organism to different substances and of different species or even strains of the same species of Mycobacterium to the same substance. Streptomycin is also highly effective against various related organisms, namely, Erysipdothrix and actinomy-cetes, comprising both saprophytic and parasitic strains, with considerable variation among different species.

Bacteriostatic and Bactericidal Substances Produced by a Soil Actinomyces.

Summary The bacteriostatic and bactericidal substance produced by a soil Actinomyces was shown to consist of 2 compounds, designated as “actinomycin A” and “actinomycin B”. The first is highly pigmented (red) and is soluble in ether, ethyl alcohol and water, but not in petrol ether; it gives a clear solution in water. The second is soluble in ether and in petrol ether, soluble with difficulty in alcohol, but not in water. The first (A) is highly bacteriostatic, many Gram-positive bacteria being inhibited by dilutions of 1:100,000,000; the Gram-negative bacteria are inhibited only by higher concentrations, namely, 1:5,000 to 1:100,000; this substance is only weakly bactericidal. The second substance (B) is weakly bacteriostatic, but more actively bactericidal. Although Gram-negative bacteria are as a rule more resistant against the actinomycin than the Gram-positive forms, there is no sharp line of demarcation between the two groups. Marked differences in sensitivity exist between the bacteria within each group.

Streptothricin, a New Selective Bacteriostatic and Bactericidal Agent, Particularly Active Against Gram-Negative Bacteria.∗

Summary A new type of antagonistic substance, designated as streptothricin, has been obtained from a soil Actinomyces. The substance appears to be formed from certain amino acids in the medium. Streptothricin is insoluble in ether, petrol ether or chloroform, and is carried down by precipitating the medium with ethyl alcohol. It is best separated from the medium by adsorption on norit-A, followed by elution with dilute mineral acid. Further concentration is accomplished by neutralization of the acid and concentration in vacuo. The active substance is low in nitrogen, is not affected by proteolytic enzymes and can withstand 100°C, for 15 minutes. Its properties are those of an organic base. The bacteriostatic action of streptothricin is unique. The addition of 0.1 mg of crude material to 10 cc of nutrient agar inhibits the growth of E. coli and various other gram-negative bacteria; among the gram-positive bacteria, some, like Bac. subtilis and micrococci, are more sensitive, whereas others, like Bac. mycoides, are far more resistant. Streptothricin possesses also marked bactericidal properties, especially upon certain gram-negative bacteria.

Candicidin, A New Antifungal Antibiotic

A group of 197 cultures of actinomycetes were tested for their antibiotic activity against Cerastostomella ulmi. This screening program yielded a strain of Streptomyces griseus which produced an an...

Three Decades With Soil Fungi

To Dr. Charles Thorn, recently retired from his position as Microbiologist in the Bureau of Plant Industry, Soils, and Agricultural Engineering, U. S. Department of Agriculture, who has contributed in a large measure to the development of our knowledge of the fungi of the soil by encouraging many younger workers, including the writer of these lines, by helping them with the identification of the fungi that they have isolated from the soil, and by devoting his whole life to the advancement of the knowledge of fungi, notably those that inhabit soils, composts, and food products, this paper is gratefully dedicated.

DECOMPOSITION OF ORGANIC MATTER IN SEA WATER BY BACTERIA III. FACTORS INFLUENCING THE RATE OF DECOMPOSITION

1. Investigations are reported on the decomposition of organic matter in sea water placed under controlled laboratory conditions. It has been found that, under these conditions, the organic matter in the water, both in suspension and in solution, can undergo rapid decomposition. It is quite possible that a change in temperature, resulting from the sudden warming up of the water, may bring about not only an increase in the biological reactions, but also a change in their very nature; this limitation need not invalidate the results obtained, since these results are not a measure of what actually happens in nature under different conditions, but what may happen under any one set of conditions.2. The abundance of readily decomposable organic matter in sea water was measured by the rate of oxygen absorption in the water, incubated under uniform conditions. The rapidity of libenation of nitrogen in the decomposition of the organic matter can be measured by the rate of decomposition of glucose added to the water...

The Role of Antibiotics in Nature

It has long been recognized that natural substrates harbor two kinds of microbes:1 (a) those that are pathogenic, capable of causing diseases in man, animals, and plants, and have to be constantly combated for man to survive; these represent one of the major problems of the human race; (b) those that are saprophytic, non-injurious or even beneficial to man; these are the universal scavengers; they are necessary for the growth of our crops and for a number ofother essential processes. It has also been known for a long time that some of the saprophytic microbes can interfere with the growth ofpathogenic and other microbes; that some can form chemical substances, or antibiotics, that suppress the growth ofpathogenic microbes, comprising bacteria, protozoa, and fungi. This knowledge remained until very recentlymore in the realm ofscientific curiosity than of practical application, although attempts were made at various times to utilize this property for the practical control of infectious diseases.

PRODUCTION OF ANTIBIOTIC SUBSTANCES BY ACTINOMYCETES

It has now been definitely established that a considerable proportion of all actinomycetes that can be isolated from soils or other natural substrates have the capacity of inhibiting the growth of, and even of destroying, bacteria and other microorganism.5 This was brought out emphatically in several of the surveys that have been made on the distribution of antagonistic properties among actinomycetes.1, 2, 4, 6, 10 Twenty to 50 per cent of all the cultures tested, whether freshly isolated from natural substrates or taken from culture collections, were found to possess antagonistic properties. The selective antimicrobial activities of actinomycetes differ greatly, both quantitatively and qualitatively, as could easily be demonstrated by their respective antibiotic spectra. The nature of the active agents or the antibiotics produced by these organisms depends upon the species; frequently upon the strain; the composition of the medium in which it is grown, and the conditions of cultivation.7, 8 Several distinct antibiotics have now been isolated from cultures of actinomycetes. Some, namely, actinomycetin, micromonosporin, mycetin, and actinomyces lysozyme, have been only partly purified, whereas others, including actinomycin, proactinomycin, streptothricin, and streptomycin, have been isolated and crystallized. These substances differ greatly in their chemical structure, antimicrobial properties, toxicity to animals, and in vivo activity. Some of the antibiotics are produced in simple synthetic media; others are formed in complex organic substrates; still others, like streptomycin, require the presence in the medium of a specific nutritive substance, an “activity factor,” which is either a precursor or a prosthetic group of an enzyme system essential for the production of the antibiotic agent. Although this “activity factor” can be synthesized by Streptomyces griseus, its addition to the medium favors the rapid production of streptomycin. Streptomyces griseus can, therefore, grow

MARINE BACTERIA AND THEIR RÔLE IN THE CYCLE OF LIFE IN THE SEA I. DECOMPOSITION OF MARINE PLANT AND ANIMAL RESIDUES BY BACTERIA

The synthesis of organic matter in the sea through the agency of the chlorophyll-bearing plants, ranging from the smallest diatoms to the largest algae, consists in the assimilation of the carbon as CO2, of the nitrogen as nitrate, and probably to a lesser extent as ammonia and nitrite, of the phosphorus as phosphate, and of other elements in lower concentrations. Before these elements can be returned to circulation, after the plants as well as the animals which fed partly upon them die, the complex organic substances have to be decomposed through the agency of bacteria. If one is to judge by analogy with the decomposition processes which take place on land, the liberation of the elements in a mineralized form does not represent a simple process, but rather a chain of processes. The rate of liberation of the elements by bacterial action depends primarily upon the chemical composition of the materials undergoing decomposition and upon the organisms active in the decomposition processes. The following investigations were undertaken for the purpose of determining to what extent the chemical composition of marine residues of plant and animal origin influences the rate of their decomposition by marine bacteria and the rate of liberation of the important elements, especially nitrogen, in. an available form. It was further essential to obtain light upon the mechanism of decomposition of some of the chemical constituents of the marine residues by specific members of the bacterial population of the sea. These investigations can be classified, therefore, under three distinct headings, namely: (1) the chemical composition of marine zo6plankton and of certain marine algae, (2) the decomposition of the plankton and algal material in sea water and in marine